NGC LIN

.o ?

NLN.003605
NH XUT BN I HC QUC GIA H NI

 NGC LIN

MIN DCH HC
C S
(n ln th hi, c sa cha v b::img)

NH XUT BN I HC QUC GIA H NI

16 Hng Chui - Hai B Trng - H Ni

in thoi: (04) 7685236; (04) 9715012. Fax: (04) 9714899
Email; nxb@hn.vnn.vn

C h u tr c h n h im x u t bn:
Gim c:

PHNG QUC BO

Tng bin tp:

PHM THNH HNG

C h iu tr c h n h im n i du n g:

Ngi nhn x t :

GS.TS NGUYN n h b n g
GS.TS TRUNG PHN
PGS.TS NGUYN NH HIN

B in t p t bn:

MNH CNG

C hbn:

NG TH H

T rn h b y ba:

NGC A N H

MIN DCH HC c s
M s: 1K-04035-02204
In 1000 cun, kh 16 X 24 ti Nh in i hc Quc gia H Ni
S xut bn; 120/113/XB-QLXB ngy 10/2/2004. S'trch ngang: 73 KH/XEB
In xong v np lu chiu qu II nm 2004

III

l/lc lc

Chng I. Khi nim c bn v min dch hc

.1. nh ngha v min dch hc

3
.2. Lch s nghin cu min dch hc
3
.3. Nhng khi nim tng qut v min dch hc
6
].3.1. Min dch tip thu hoc thch ng v min dch t nhin
6
].3.2. Cc khng nguyn (antigens)
10
1.3.3. Cc khng th v b th
10
1.3.4. Cc xitokin (cytokine)
12
1.3.5. Hin tng phn v (anaphylaxis)
13
1.3.6. Ci bn thn v khng phi bn thn (self,nonsel) 14
1.3.7. Cc phn ng khng nguyn - khng th in vitro
14
1.3.8. Cc loi p ng min dch v l thuyt la chn dng
14
1.3.9. S tim chng (vaccination)
15
1.3.10. S iu ha min dch
15

Chng II. Khng nguyn

19

i. 1. nh ngha v khi nim chung v khng nguyn

19
:.2. Phn ng cho
20
.3. Hapten v protein mang
21
;.4. Tnh khng nguyn ca cc cht sinh trng hp (biopolymer)
21
!.5. S thch ng ca cc vi sinh vt bng cch ci bin cc 23
khng nguyn ca chng
:.6. Immunogen v kh nng p ng min dch
24
'm tt chng II
25

Chng ni. Cc khng th v th th ca khng nguyn

27

!.l. Cu trc chung ca cc immunoglobulin (Ig)

;.2. Cu trc phn t ca cc immunoglobulin ring bit
:.3. M quan h gia cu trc v chc nng ca cc khng th
;.4. C s di truyn v tnh a dng ca khng th
;.5. Cc khng th n dng (monoclonal antibodies)
;.6. Khng th ti t hp (recombinant antibody - rAb)

27
31
37
37
43
44

IV

______________________________________________________________

3.7. Cc th th ca lympho B (BCR )

3.8. Cu trc ca cc th th lympho T (TCR)
Tm tt chng III

Chng IV. Cc phc h ph hp t chc ch yu

45
46
50'

51

4.1. M u
51
4.2. Cu trc chung ca h thng HLA
52
4.3. Cu trc cc phn t v h( gen ca HLA
53>
4.4. S phn b, iu ho biu hin v chc nng ca cc 55)
plin t HLA
4.5. H thng HLA lin quan n qun th chng tc v cc 5B
bnh l
4.6. Cc phng php nghin cu h thng HLA
58
Tm tt chng IV
60

Chng V. B th
5.1. Khi nim
5.2. Cc protein ca b th
5.3. Cc tin trnh hot ho b th
5.3.1. Con ng ht ho c in
5.3.2. Con ng hot ho b th nh lectin MB
5.3.3. Con ng hot ho bn cnh v cc yu t hot
ho b th
5.4. Hiu qu sinh hc ca s hot ho b th
5.5. B th v cc c ch trh thot ca vi sinh vt
5.6. Cc h thng khc ca huyt tng tham g^ia vo cc c
ch bo v v c ch vim
5.7. Cc bnh ly pht sinh do thiu ht b th bm sinh
Tm tt chng V

6]l
6]l
62
6?3
6.3
64
69
6J9
72
72
74

Chng VI. Phn ng khng nguyn - khng th

v cc k thut ha sinh min dch
6.1. Phn ng khng nguyn - khng th
6.1.1. Cc c tnh chung ca s lin kt khng nguyn khng th
6.1.2. Cc c im v cht lng v s lng ca phn
ng khng nguyn - khng th
6.1.3. Phn loi cc phn ng khng nguyn - khng th
6.2. Cc k thut min dch
6.2.1. K thut kt ta trong mi trng lng

7!5
7.'5

7'7
7 8
79
7/9

6.2.2. Xt nghim khuch tn min dch theo Ouchterlony 80

6.2.3. in di min dch khuch tn (ImmunodiTusion 80
electrophoresis)
6.2.4. Cc phng php ngng kt min dch (Immuno - 81
agglutination)
6.2.5. Cc phng php min dch s dng b th
81
6.2.6. Cc k thut min dch s dng thuc th nh du
83
6.2.7. K thut min dch phng x
84
6.2.8. K thut min dch lin kt enzim (ELISA)
85
Tm tt chng VI
86

Chng VII. Cc c quan v t bo ca h

min dch, bit ha v chc nng

87

7.1. C quan ngun

7.2. Cc c quan s cp
7.2.1. Tuyn c (Thymus)
7.2.2. Ti Pabricius v ty xng
7.3. Cc c quan lympho th cp
7.4. Ngun gc cc t bo ca h min dch
7.5. Cc t bo thuc dng lympho, bit ha v chc nng.
7.5.1. c im chung ca s bit ha cc t bo lympho
7.5.2. S bit ha ca lympho T v du hiu khng
nguyn bit ha
7.5.3. S bit ha lympho B
7.5.4. S bit ha cc dng t bo khc theo chc nng
rrin dch
Tm tt chng VII

87
87
88
88
89
89
91
91
92

Chng VIII. S tng tc gia cc t bo min dch

v iu ho p ng min dch

103

95
96
101

8.1. S tng tc gia cc t bo c thm quyn min dch

103
8.1.1. Hp tc i thc bo - lympho T v trnh din 104
khng nguyn
8.1.2. Hp tc lympho Th - lympho B
109
8.2. S iu ho p ng min dch
111
8.2.1. iu ho p ng min dch bng cc khng th v 112
mng li idiotip
8.2.2. iu ho p ng min dch nh cc t bo lympho T 114
8.2.3. iu ho p ng min dch bng kim tra di truyn
115

VI

8.2.4. iu ho p ng min dch nh s tng tc min

dch - thn kinh ni tit
Tm tt chng V III

Chng IX. Min dch bnh l qu mn

9.1. Khi nim chung v min dch bnh l
9.2. Cc hin tng qu mn
9.2.1. Qu mn phn v do IgE
9.2.2. Qu mn c hiu kiu II v III do IgM v IgG
9.2.3. Qu mn trung gian t bo hay qu mn mun
9.2.4. Qu mn do kch thcl'. *ikiu V)
Tm tt chng IX

Chng X. Min dch chng vi sinh

v min dch ung th
10.1. Min dch chng vi sinh vt
10.1.1. Cc c ch t nhin v thch ng loi tr vi sinh
vt nh lp da v tuyn nhy
10.1.2. Phn ng vim ti ch v h thng chng li nhim trng
10.1.3. p ng min dch c hiu chng nhim khun
10.2. Min dch ung th
10.2.1. Khi nim ung th, cc gen ung th v km hm
ung th
10.2.2. p ng min dch c hiu chng ung th
10.2.3. Min dch t nhin chng ung th
10.2.4. Liu php min dch v min dch phng tr ung th
10.3. Hi chng tng sinh min dch v cc bnh ung th
10.3.1. Khi nim
10.3.2. Tih n dng ca bnh tng sinh min dch lympho
10.4. Mt s'c im lm sng ca ung th
10.4.1. Ch th ung th (Tumour marker)
10.4.2. Phn loi ch th ung th theo kh nng c hiu bnh
10.4.3. Mt s" ch th ung th lin quan vi bnh
Tm tt chng X

Chng XI. Min dch bnh l:

thiu ht min dch v hi chng suy
gim min dch mc phi (AIDS)
11.1. Khi nim

] 1(5
] 19

121
121
122
122
123
127
129
130

] 33
133
134
134
134
136
136
137
138
139
140
140
140
147
147
148
148
152

153
153

_______________________________________________ V_
11.2. Thiu ht min dch nguyn thy ca cc t bo B
11.2.1. Bnh khng c Y- globulin trong mu
11.2.2. Thiu ht IgA, cc phn lp IgG v tng IgM
11.3. Thiu ht min dch nguyn thy ca cc t bo T
11.3.1. S pht trin bt thng ca t bo ngun lympho
giai on sm ca s bit ha
11.3.2. Biu hin thiu ht cc phn t phn lp II ca MHC
11.3.3. Hin tng mt iu ha gin mao mch do di truyn
11.3.4. Thiu ht cc protein kt dnh bch cu
11.4. Thiu ht min dch cc thc bo v b th
11.5. S thiu ht min dch th cp v AIDS
11.5.1. Cc bnh v mu v ung th
11.5.2. Thiu ht min dch do ri lon trao i cht
11.5.3. Bnh AIDS v con ng ly truyn
Tm tt chng XI

Chctog XII. Dung np min dch v bnh t min

153
153
154
154
154
155
155
155
155
156
156
156
156
163

165

12.1. Dung np min dch

12.1.1. Khi nim
12.1.2. Cc c ch to ra dung np min dch
12.2.2. Cc t khng nguyn tham gia
12.2.3. Cc nguyn nhn ca bnh t min
12.2.4. Cc c ch hiu qu ca bnh t min
'Tm tt chng XII

165
165
166
167
168
169
171

Chng XIII. S tin ha min dch ca

cc loi ng vt

173

13.1. M u
13.2. Kh nng min dch ng vt khng xng sng
13.2.1. Cc biu hin t bo ca h min dch
13.2.2. Cc cht ha gii ha hc
13.2.3. Cc phn ng min dch ng vt khng xng sng
13.3. Kh nng min dch ca ng vt dy sng v c
xng sng
13.3.1. Cc ng vt hi tiu
13.3.2. Cc ng vt c xng shg bc thp
13.3.3. c im min dch ca cc lp c xng
13.3.4. c im min dch ca ng vt bin nhit
13.3.5. c im min dch ca cc loi chim
13.3.6. c im h min dch ca b linh trng

173
174
174
174
175
176
176
177
177
179
180
184

V II______________________________________________________________

Tm tt chng X III

Chng xrv. Phng v cha bnh

bng liu php min dch
14.1. Vi nt lch s
14.2. Tim chng, vacxin phng v cha bnh
14.2.1. Nguyn tc chung ca vacxin
14.2.2. Cc dng vacxin ang c nghin cu v s dng
14.3. Liu php min dch khng th
14.4. S dng cc thuc km hm min dch
14.5. S dng cc xitokin v antixitokin
14.6. Liu php min dch t bo
14.7. Liu php gen chng ung th

Chng XV. Min dch trong cy ghp

15.1. Khi nim v phn loi cy ghp
15.2. Cc c ch thi b mnh ghp
15.3. Phn loi cc phn ng thi b mnh ghp
15.4. Mt s' c im lm sng trongcy ghp
15.4.1. C th cho mnh ghp hoc cquan
15.4.2. C th nhn mnh ghp
15.5. Liu php km hm min dch trong cy ghp
15.6. Mang thai l trng thi t nhin ca cy ghp d gen

1912

19
195
19(6
19(6
19'7
20(0
20'4
20.'5
20>8
209

21 1
211
2i;2
2l'4
2li5
2li5
21(6
21(6
2l8

Cu hi n tp min dch c s
Mt s dng cu hi min dch

22 1
22(6

Ph lc

231

Ph lc I. c im cu trc v chc nng ca cc khng

nguyn CD
Ph lc II. Gii ngha danh t min dch

233

Ti liu tham kho

339

275

Li gii thiu

Sch Min dch hc c sc bin son nhm p ng yu

cu dy v hc mn min dch hc cc trng i hc Khoa hc
t nhin, i hc S phm, i hc Nng nghip, i hc Y, i
hc Dc. Sch l ti liu tham kho i vi cn b ging dy v
l ti liu hc tp cn c i vi sinh vin.
Sch cung cp nhng kin thc rt c bn, kinh in v cp
nht v min dch hc, mt mn hc c lch s pht trin mi hn
so vi nhiu mn hc khc.
Sch gm 15 chng c kin trc mt cch h thng, ph
hp vi logic nhn thc. Tc gi - PGS.TS Ngc Lin rt
thnh cng trong la chn lng thng tin min dch hc cn v
cng nh trong cch thc hiu t chnh xc, d hiu cun
sch xng ng l sch gio khoa ca cc trng i hc c tm cd
thuc i hc Quc gi.
Ti c vinh hnh gii thiu sch "Min dch hc c s" cng cc
bn c.

H Ni, ngy 5 thng 8 nm 1999

Nguyn inh Bng
Gio s Tin s Y khoa
Gim c Trung tm Quc gia
Kim nh Sinh vt phm

Chng I. Khi nim c bn v min dch hc

1.1. nh ngha v min dch hc

Danh t Immunus theo ngha nguyn gc l c min
gim . Tnh trng u tin min gim mt s" bnh truyn nhim
nh bnh u ma (variole) bnh si (rougeole) v mt s' bnh
khc v.v... c bit t lu nhng ngi b mc bnh mt
ln. Tt c c th sng cn c c tnh quan trng l nhn bit v
dung np nhng ci ca bn thn (SelO. ng thi nhn bit v
thi b nhng ci khng phi ca bn thn (NonselO. xa l i
vi c th. Min dch hc l mt mn khoa hc sinh hc v y hc
chuyn nghin cu cc qu trnh nhn bit cc cht l, gi l
khng nguyn (antigen) v hu qu ca s nhn bit , l s
p ng min dch (immune response). S nhn bit ny c c
l do kh nng tng tc ca mt phc h cc t bo trong h
min dch ca c th ngi v ng vt.

1.2. Lch s nghin cu min dch hc

Min dch hc (mmunology) ngy nay tr thnh mt mn
khoa hc. Tuy ch mi tn ti khong trn 100 nm nay nhng
s ng gp ca n cho cc ngnh sinh hc ni chung v y dc
hc ni ring ngy cng thy r. Nhng pht minh ch yu trong
lnh vc nghin cu min dch hc theo thi gian c trnh by tm
tt nh sau:
Nm 1881-. Nhng tng v tnh min dch (Immunity) ln
u tin c Luis Pasteur v Koch xng. Tip theo ,
hin tng thc bo (Phagocytosis) c Metchnikoff quan st
thy. K thut vacxin phng bnh di chnh thc c Luis
Pasteur p dng. Nm 1890, cc nh bc hc Von Behring v Eh-

lich pht hin ra khng th (antibody) v tm ra v tr cc th

th (receptor) mng t bo. Vo thi k ny k thut iu tr
bnh bng huyt thanh, hin tung ngng kt t bo, hin tng
kt ta, kh nng chn on bnh theo huyt thanh c
nghin cu v ng dng trong y hc (Roux, Charriu, Widal v
Kraus).
Nm 1900: Richet v Potier pht hin ra hin tng phn v
(Anaphylaxis), Bordet v Arthus tm ra cc b th v hin tng
Arthus, Landsteiner tm ra cc khng nguyn nhm mu ABO
ca ngi, Wright tm ra hin tng Opsonin ha (Opsonization).
Nm 1910: nh du s pht minh ra cc hapten ca Landsteiner.
Nm 1920: L thuyt v mng li do Heidelberger v Marrack xng. K thut ng dng cht gii c (anatoxine) v
tim chng (vaccination) ca Ramon v Gleny c thc hin.
Nm 1930: nh du vic pht minh ra cc gama globulin ca
Tiselius v BCG ca Calmette v Gurin.
Nm 1940: Snell tm ra qui lut cy ghp m t bo, Medawar
tm ra hin tng dung np (tolerance) gip cho vic iu tr
cc bnh min dch sau ny. Bn cnh , cc k thut min dch
hunh quang (ImmunoAuorescence) ca Coombs v Coons,
khuch tn min dch (Immonodiffusion) ca Oudin c p
dng.
Nm 1950: L thuyt la chn dng ca Burnet ra i m
ra kh nng tm hiu tnh a dng ca khng th trong p ng
min dch. Vo nhng nm , cc nghin cu su sc v cu
trc v chc nng ca cc globulin min dch (Immunoglobulin)
c Porter v Edelman tin hnh.
Nm 1960: M du vic pht minh ra vai tr ca tuyn c
(Thymus) do M iller thc hin. Tip theo , Ishizaka tm ra cc
gen ca hin tng p ng min dch, Jean Dausset tm ra
phc h ph hp t chc ch yu (Major Histocompatibility
Complex) c mt bch cu ca ngi nh mt khng nguyn
ph hp t chc v c gi l HLA (Human Leucocyte Antigen).
Nm 1970: Jerne ra l thuyt mng li Idiotype v s hp
tc t bo trong p ng min dch. Trong nm 1975, Mifetein v
Kohler da vo l thuyt la chn dng tm ra k thut lai t
bo cho php sn xut cc khng th n dng (Monoclonal antibodies).

Nm 1980: Tonegavva m u cc pht minh v c tnh di

truyn ca cc immunoglubulin v cc th th T. Nhng nm
1981 tip theo, nhm nghin cu ca Montagnier vin Pasteur
Paris pht hin ra virus HIV gy bnh suy gim min dch
mc phi (AIDS) cho con ngi.
Nhng nm gn y, cc pht minh ca min dch hc phn t
(Molecular Immunology) mang li nhiu li ch to ln cho cc
ngnh sinh hc v y dc hc c v l lun v ng dng thc
tin. Bn cnh , nhng tin b trong nghin cu v sinh hc
phn t c ng dng cho lnh vc y hc v min dch hc.
Chng hn, ngi ta pht hin ra s dung hp gen bcr/ abl
trong bnh ung th bch cu (leukemia) ngun gc ty xng
trng thi mn tnh, phn tch trnh t genom ca HlV v
pht minh ra phng php nhn dng tuyn chn ADN in vitro
(gi l phn ng dy chuyn polymeraz - PCR). Phng php
PCR kt hp vi phng php phn tch tnh a hnh v chiu
di ca mnh ct' gii hn trong phn t ADN (RFLP) cho php
pht hin c bnh thiu ht min dch hoc t bin gen di
truyn cc bnh nhn. Trong nhng nm gn y, ngi ta
tm ra gen p. 53 l gen chng ung th (1989).
Nm 1990: Chng minh trc tip (ex vivo) kh nng chng ung
th ca gen RB. Trong nhng nm sp ti chc chn s c nhng
pht minh quan trng v min dch phn t mang li nhiu li
ch cho khoa hc sinh hc v y dc hc. c bit mi y ngi
ta tm ra kh nng gy bnh truyn nhim ca mt dng
phn t protein gi l cc PRION. Vi thnh cng ny nh khoa
hc M, tin s Stanley Prusiner nhn gii thng Nobel v y
hc (1997). Thnh cng ny d m ra mt quan nim mi:
Khng ch cc vi sinh vt, virus gy bnh truyn nhim cho
ngi v ng vt m c mt s phn t protein cng c kh
nng ny.

1.3. Nhng khi nim tng qut v min dch hc

1.3.1.Min dch tip thu hoc thch ng v min dch t nhin

Tnh min dch (Immunity) c hiu l kh nng bo v ca
c th chng li nhng tc nhn gy bnh xm nhp t bi
ngoi. Cc tc nhn gy bnh c th l yu t truyn nhim bnh
nh VI sinh vi (vi khun, vi nm. virus v cc c tca chng),
cc (-n trng, k sinh trng v cc protein l gy c cho c th.
Hng ngn Iim trc cng nguyn, ngi Trung Hoa bit
bo v cho con ngi bng cch s dng mn vy ca ngi
khi bnh du ma ch xt ln vt xc da ca ngi cha mc
bnh d gy min dch cho ngi chng li c<n bnh ny. Nm
1798. Jenner Anh d thc hin li phng php ny nhm bo
v cc con b. trnh b bnh u ma tru b. Nh cc nghin
cu ca Louis Pasteur v trng phi ca ng (1880 - 1890),
phng php tim chng (Vaccination) gy min dch kiu trn
c nghin cu v p dng cho con ngi.
Tt c cc p ng min dch ca c th trc tin bao gm s
nhn bit tc nhn gy bnh hoc nhng cht l, tip theo l
nhng phn ng nhm loi b chng ra khi c th. Nhng p
ng min dch ni chung c th phn ciia thnh hai lp ln l
dp ng min dch t nhin (hoc bm sinh) v p ng min
dch thch ng (hoc p ng min dch tip thu). p ng min
dch thch ng (hoc tip thu) c tnh dc hiu cao i vi mt tc
nhn gy bnh ring bit. S p ng ny ngy cng c hon
ihin sau mi ln lip xc vi cng ml loi vi sinh vt. H thng
min dch dc hiu c th ghi nh li tc nhn gy bnh v ngn
cn tc ng gy bnh ca chng ln tip xc lp li tip theo,
(hi nh min dch l mt c tnh quan trng ca nhng loi
thc vt bc cao trong nc thang tin ho. c tnh ny l c s
khoa hc cho liu php min dch tim chng.

Hnh 1.1 S vng tun hon t bo kt hp gia min dch

t nhin v min dch tip thu vi s tham gia ca cc thnh
phn trong min dch dch th v min dch trung gian t bo.
Cc p ng min dch ch yu c thc hin l do hot ng
ca nhng bch cu (leucocyte). Cc bch cu ny bao gm cc t
bo lympho (lymphocyte) dng B, T, lympho cha ht to trong t
bo cht, cc thc bo (monocyte, macrophage), cc t bo bch
cu trung tnh (neutrophil leucocyte), bch Gu a axit (eosinophil ieucocyte), cc t bo ph tr (accessory cell) gm bch cu
a kim (basophil leucocyte), cc t bo mast (mastocyte), cc t
bo dng tm cn gi l tiu cu (platelet cell, thrombocyte) v
mt s t bo ca m nh t bo Langerhan, Kupffer.
Cc t bo thc bo n nhn (MNP: mononuclear phagocytes)
l thnh phn quan trng nht ca thc bo c i sng lu di
v bt ngun t t bo ngun ca ty xng. Chc nng ca
chng l bt gi cc vt th l trong bao gm c cc tc nhn
gy bnh, nut v ph hy chng. Cc t bo ny thng khu tr
nhng ni c th d dng n bt cc vt th l. Chng hn
cc t bo Kupffer ca gan, cc t bo ca mng hot dch nh
khu bao quanh khoang khp. Trong mu c cc t bo mono
(monocyte) c th di chuj'n v pha cc m v tr thnh i thc
bo ca m. Cc t bo ny c th trnh din cc khng nguyn
cho cc t bo lympho - T rt c hiu qa. Dng th hai ca Idp

t bo thc bo l cc t bo a nhn trung tnh (PNN: Polynu

clear Neutrophil) chim t l cao trong cc bch cu ca mu.
TB Dgun tu
xucnog t di mi
Y'u t hoi hoa TB nguD

t
TB khcri tbu dng lympbo

TB khi thu ng tu

Q
L7
Erythropoklin
4

Tuyn c: IL7,
cc IL khc

I U , GM-CSR ILl, IL6

Tbrombopoet, ,

IL ll

5
Lympbo B

Lympho T t nhin,

Nguyn bo
bg<AuCFU

TnmD
T bo nhn bcheu

kbngl

TinlhD
Ta thn bch cu
bachcu
ht Y mio
Xt
IU,GMCSF,
IL3.GM.CSF,
G-CSF
M-CSF
1L5

HDgcu

Tucu

Bch cu
kni

'

Bch cu
axit

< t
Bch cu
trng lih

TB moo

Hinh 1.2 Ngun gc ca cc t bo h min dch

v cc yu t tham gia bit ho t bo.

Chng c th di chuyn v pha m p ng vi mt s kch

thch. Tuy nhin cc l bo ny c di sng ngn, d cht sau khi
bat gi v nut cc vt th l.
Cc t bo lympho hoc lympho (lymphocytes) c chc nng
nhn bit c hiu cc vi sinh vt p ng min dch thch
ng. Tt c cc lympho u bt ngun t cc t bo ngun ca
ty xng v c chia thnh hai dng qun th (population) l
lympho-T v lympho-B. Cc h'mpho-T c pht trin v chn
mi tuyn c (Thymus) nn c k hiu l T. Cc lympho-B
c pht trin trong tu xng (Bone marrow) cc ng vt c
v trng thnh, nhng co loi chim lympho-B pht trin v
chn mi ti Pabricius (Pabricius Bursa). V th cc t bo
Ivmpho ny c k hiu l B. Mi t bo B nhn bit mt khng
nguyn ring bit nh mt th th (Receptor) c hiu nm trn
b(1 mt t bo ca n. Tip theo giai on nhn bit, t bo B s
phn chia v bit ho thnh cc t bo plasma (plasmocytes) c
kh nng tit ra phn t th th dng ho tan c gi l
khng th (antibody).
Cc t bo T tip tc c bit ha ph hp vi chc nng ca
cling thnh hai dng t bo l T bi tr (T-helper: TH) c du
hiu bit ho khng nguyn trn b mt t bo l CD4 (t ch
m hay cm bit ho - Cluster of Differentiation) hoc gi tt l
T, v mt dng T gy c cho t bo (cytotoxic lympho-T). vit tt
l Tc c du hiu bit ho khng nguyn b mt t bo l CD8
cn gi l T8. Qun th ph (subpopulation) TH li bit ho
thnh hai dng, mt dng tng tc vi t bo B gip cho s bit
ha v tong hp khng th ca t bo B, mt dng khc gi tt l
TD tham gia vo hin tng qu mn mun (delayed hypersensivity) ca qu trnh min dch qua trung gian t bo tng tc
vi thc bo n nhn hoc i thc bo gip cho vic ph hy
cc tc nhn gy bnh.
Mt nhm t bo khc gi l cc lympho c ht ln trong t bo
clit, vit tt l LGL (Large Granular Lymphocyte) cng c kh
nng nhn bit cc t bo ung th v cc t bo b nhim virus
v;\ ph hy cc t bo ny. Tuy nhin cc t bo LGL khc vi
lympho-Tc l chng s dng h thng nhn bit khng c hiu.
V th cc t bo LGL cn c gi l cc t bo git t nhin
TNK (Natural killer-T). Cc i thc bo ny chng hn nh
LGL cng c kh nng nhn bit v ph hy cc t bo ung th

10

v nhim khun hoc cc tc nhn gy bnh b bao ph bng cc

khng th c hiu (Xem hnh 1.3, 1.3, 1.4).
Mi loi t bo lympho (T v B) u c cc du hiu bit hoi
khng nguyn ring bit, c bn cht l cc glycoprotein, to rai
cc th th b mt t bo tham gia vo qu trnh tng tc min
dch. Chi tit v cu trc phn t ca cc du hiu bit hoi
khng nguyn s c trnh by cc chng tip theo.

1.3.2. Cc khng nguyn (antigens)

Ngy nay ngi ta c th nh ngha khng nguyn l bao gmi
tt c nhng cht c nhn dng bi cu trc nhn bit tng
ng nm trn khng th hoc nm trn cc th th ca cc lym pho. V tr cu trc trn mt phn t khng nguyn c th phni
ng vi mt kiu cu trc ho hc ca phn t khng th hoa'
phn t th th c gi l quyt nh khng nguyn (antigenicdeterminant) hay l epitop. Phn phn t tng ng ca khng
th lin kt vi khng nguyn c gi l paratop. Mt khng
nguyn c th c mt vng khm (mosaic) ca cc epitop khc:
nhau hoc gi l cc epitop lp li. Mt khng th ch c hiui
vi mt epitop ch khng phi vi ton b phn t khng
nguyn. Cn cc lympho-T thng nhn bit cc khng nguyni
c trnh din trn b mt ca cc t bo vt ch khc dii
dng nhng mnh peptit nh. Chng hn, mt t bo b nhimi
bi mt virus s bc l cc mnh peptit ca protein virus trn b;
mt ca n. iu ny lp tc s c nhn bit bi cc t bo T
gy c, lm cho cc t bo vt ch nhim virus s b tiu dit
Cc mnh khng nguyn c trnh din lin kt vi cc phn t
protein chuyn ha nm trn cc t bo bch cu c bit l ccc
t bo APC, cc t bo B v T. Cc phn t protein ny l sn>
phm ca mt tng th cc gen m ho cho phc h ph hp t)
chc ch yu (MHC: Major Histocompatibility Complex). Cc;
phn t ny c vai tr c nh cc mnh peptit khng nguyni
c gi l cc phn t ca MHC.

1.3.3. Cc khng th v b th
Von Behring (1890) chng minh rng huyt thanh ca mtt
ng vt gy min dch chng li c t' ca bnh bch hu c)

11

ha mt cht trung ha c c t" . Cht ny c ng gi l

khng th (antibody) ngha l mt loi protein c c tnh chng
li cc th vi khun gy bnh. Tt c cc phn t khng th ngy
Iiay c chng minh l cc globulin c chc nng min dch
(vit tt l Ig: Immunoglobulin) v c bn ch"t glycoprotein. Cc
khng th c chia lm 5 lp ty theo cu trc v chc nng
min dch l IgG, IgA, IgM, IgD, IgE. Cc phn t Ig c c tnh
hot ng sinh hc theo hai chc nng:
;i. C kh nng lin kt vi khng nguyn t nht hai v tr tip
nhn vi khng nguyn. Kh nng lin kt vi khng
nguyn c c i do s bin i k diu ca phn tn cng
NH2 trn phn t khng th.
b. Mt khc, phn tn cng COOH ca phn t khng th c
kh nng thc hin mt s ln cc hot ng sinh hc di nh
hng ca s lin kt vi khng nguyn. Tt c cc khng th
u c cng mt cu trc phn t nhng khc nhau mc
ca vng lin kt vi khng nguyn.
Trong a s trng hp, mi khng th lin kt c hiu vi
ch mt khng nguyn. Cc phn t khng th c coi l nhng
cht rt d thch ng v tng tc rt linh ng vi cc yu t
ca h thng min dch nhn bit c hiu cc vi sinh vt
cng nh cc sn phm ca chng. Nhn chung, phn t khng
th c chia lm hai phn: Fab l phn lin kt vi khng
nguyn (Fragment antigen binding). Fc (Pragment cristallisable)
l phn d kt tinh phn ng vi cc t bo ca h thng min
dch qua cc th th ca cc t bo. Do , nu khng th c c
nh trn vi khun bng phn Fab th n s lin kt vi cc t
bo thc bo bng phn Fc. Hin tng bt gi vi khun v vt
th l bi cc thc bo cn c m bo bng mt b th C3b
hoc bng k h n g th. H i n tng ny c gi l s opsonin ha

(opsonization).
Tri vi khng th, t't c nhng cht l xm nhp t bn
ngoi vo c th c nhn bit bi khng th th gi l cc
khng nguyn. Tip theo vic pht hin ra phn ng khng
nguyn - khng th, Buchner (1889) v Bordet (1901) pht
hin v s dng mt yu t khng bn nhit c gi l b th
(complement, vit tt l C) gip cho vic trung ha tc nhn
truyn bnh v lm phn hy t bo vi khun, v chc nng, cc
khng th tng tc c hiu vi tc nhn truyn nhim bnh,
cn h thng b th c c" nh ln tt c cc khng th thc

12

hin chc nng min dch. H thng b th bao gm khong 40

protein bo tng c chc nng kim tra phn nfi; vi('in. Cf.c
thnh phn ca b th tng tc gia chng vi Iihau v V(i
yu t" khc ca h thng min dch. Chng hn, nhiu loi vi
khun hot ha tc thi h thng b th theo "c ch hot ho b
th hoc theo con ng lun phin ca s p ng min dcli t
nhin khng c hiu. Theo ngha ny th vi sinh vt b bao ph
bi cc protein ca b th v b bt gi bi cc thc bo. H thV.g
b th cng c hot ha bi cc khng th d c c nh t rn

b mt vi khun. y l c ch hot ho c din (classical patliway). Theo cch hot ha ny, s p ng min dch c b tli \
khng th cng tham gia thuc loi min dch c hiu. S h o a t
ha b th l mt phn ng k tip nhau t thnh phn b tl.
ny n thnh phn b th khc. S hot ha theo con dng c
hiu v khng c hiu c nhng hiu qa sau y;
1. Hin tng opsonin ha hay bao bc cc vi sinh vt c c thiK'
bo bt gi.
2. Thc bo tn cng vo cc v tr b nhim trng (hin tn
ha hng ng: chimiotactism).
3. Lm tng dng mu ti v tr hot ha v tng tnh thm ca
cc mao mch vi cc phn t ca huyt tng (plasma).
4. Gy tn thng cc mng t bo cht ca t bo. ca cc vi
khun gram m, ca cc virus c v bc v cc vi khun khc
gy nn hin tng cm ng hot ha. iu ny dn ti s
phn hy t bo. Cc chc nng chi tit ca b th s dc
trnh by cc phn sau.

1.3.4. Cc xitokin (cytokine)

Thut ng xitokin dng ch ton b cc phn t c tit 1a
bi cc t bo ca h thng min dch tham gia vo hot (ing tn
hiu gia cc t bo trong p ng min dch. Tt c cc xitokin
u c bn cht l glycoprotein hoc protein v o phn loii
nh sau:
1. Cc inteferon (IFN) c chc nng ngn nga s lan truyn ca
mt svirus gy bnh. Dng u tin gm IFNa v IFNp dc
sn xut t cc t bo b nhim virus. Dng th hai ca intcferon (IFNy) c tit ra t cc t bo T hot ho. ("c IFN
to ra s khng chhg li qu trnh nhim virus i vi t.

13

bo khng b nhim. Ngoi ra, cc IFN cn kim tra s tng

tc gi a cc lym pho v cc t bo gy c i vi cc t bo b
nhim .

2. Cc intelkin l mt nhm ln ca xitokin (t IL l n IL13)

c sn xut ch yu t cc t bo T, mc d mt s" trong
chn g c th c sn xu t t cc thc bo n n h n hoc t

cc t bo khc. Intelkin c sn xut t cc t bo lympho

th gi l lymphokin. Chng c nhiu chc nng, ch yu l
kim tra s bit ha v s sinh sn t bo. Mi mt intelkin
phn ng c h iu vi cc t bo bc l th th ri n g cho n.

'<\.Cc yu t kch thch qun lc (CSF; Clony Stimulating Factor) kim tra s phn chia v sin h sn ca cc t bo ngun v

cc t bo mu s khai (haematopoietic precursor). Chnh s

cn bng gia cc CSF khc nhau s xc nh mt phn cc t
l tng ca cc k i u t bo khc n hau c sn xu t t

ty xng. Mt s CSF cng kch thch s bit ho ca cc

bch cu bn ngoi ty xng. Mt s cc xitokin khc c th
l cc yu t hoi t ung th (TNFa v TNPp) v cc yu t
bin dng sinh trng p (TGFp) u c cc chc nng khc
nhau nhng chng c bit quan trng trong cc phn ng
vim v gy c t bo.
4. Cc cht truyn dn sinh hc (mediator): Mt s ln phn t
tham gia vo s pht trin ca cc p ng min dch ngoi
khng th, cn c mt s phn t khc c mt trong huyt
thanh. l cc protein ca giai on p ng min dch cp
tnh. Chng hn protein phn ng- c (CRP) c i lc cao i
vi protein- c ca cu khun bnh phi {Pneumococcus). Khi
CRP lin kt vi cu khun ny s to iu kin cho b th c
nh vo cu khun v kch thch thc bo bt gi vi khun
gy bnh.

1.3.5. Hin tng phn v (anaphylaxis)

Vo nm 1902, Richet v Portier gy min dch cho ch
bng mt cht c pha long tch chit t con sa. Khi tim lp
li ch't c ny cho ch, cc ng nhn thy phn ng khng
dung np lm ch cht vi liu lng khng gy c. Phn ng
ny c gi l hin tng phn v. Cc hin tng qu mn cm
khc nhau (hypersensitivity) c m t nh sau: qu mn

14

cm tc th c gi l phn v, qu mn cm gy c do cc'
phc h min dch, qu mn cm mun v qu mn cm kchi
thch. Hin tng phn v c vai tr tham gia ca khng th lp
IgE v cu trc ca chng c lm sng t (Ishizaka).

1.3.6. Ci bn thn v khng phi bn thn (self, nonself)

H thng min dch cn phi nhn bit v phn bit c c.i
bn thn v ci khng phi bn thn ngha l phn bit vW(C
nhng cht l so vi c th v nhng cht do chnh c th sinh
ra. Tuy nhin trong nhng trng hp bnh l, c th c th sn
xut ra cc khng th chng li cc cht ca bn thn gy nn
bnh l. l cc trng hp ca bnh t min (autoimmun(e
disease) c Ehrlich v Morgenoth (1902) pht hin ra.

1.3.7. Cc phn ng khng nguyn - khng th in vitro

N h tn h c h iu phn ng m in d ch k h n g nguyn - k h n g

th v nhy ca n, cc k thut xt nghim min dch

c hnh thnh cho php nh lng cc cht nng (
nanogam/ lt. l cc k thut kt ta min dch, ngng kit
min dch, phn ng c nh b th, khuch tn min dchi,
phng php dnh du min dch hunh quang v in di mim
dich.

1.3.8. Cc loi p ng min dch v l thuyt la chn dng?

Tt c cc p ng min dch din bin theo hai giai on chi
yu l nhn bit khng nguyn v phn ng loi b khng
nguyn. Trong p ng min dch c hiu, cc lympho m l)(0
cho giai on nhn bit, cn giai on nhn bit s to iu kim
cho mt qu trnh la chn dng (clonal selection). Mi mt t
bo T hoc B ch nhn bit mt khng nguyn ring bit, v toin
b, h thng min dch c th nhn bit c hiu hng nghin
khng nguyn v mi mt lympho ch nhn bit mt khn^g
nguyn. Do Burnet (1958) a ra l thuyt chn dng, the(0
th mt dng t bo min dch ch c th sn xut ra mt kiiu
khng th p ng li vi mt quyt nh khng nguyn nhit
nh. L thuyt ny c lm sng t bng k thut lai t b(0

15

ca Milstein v Kohler (1975) khi h nhn mt dng khng th

dn dng (m onoclonal antibody) c sn xu t t ch mt dng t

bo lympho.

1.3.9. S tim chng (vaccination)

Nguyn tc ca s tim chng l da vo hai c tnh c bn
ca p ng min dch thch ng. l tnh c hiu v s ghi
nh min dch. Cc t bo ghi nh cho php h thng min dch
pht trin s p ng mnh hn khi c ln tip xc th hai vi
khng nguyn. S p ng th cp ny ng thi nhanh hn v
c hiu qu hn s p ng ban u. Nguyn tc tim chng l
da vo vic ci bin cc vi sinh vt hoc c t' ca chng lm
cho chng tr nn mt tc nhn khng gy bnh nhng khng
lm mt tnh khng nguyn ca chng. V d vi khun bch hu
tit ra c t exotoxin lm ph hu cc t bo c. c t ny c
th c ci bin bng cch x l vi focmon s mt c tnh
nhng vn gi c cc epitop. Cht ny c s dng nh mt
vacxin. Mt nguyn tc khc ca tim chng l s dng ton b
cc tc nhn gy bnh truyn nhim nh virus gy bnh vim
ty xm lm bi lit tr em (poliomyelite) c lm suy yu
rn^t c tnh nhng vn gi c tnh khng nguyn ca n.

1.3.10. S iu ha min dch

- Yu t' th nht l cc lympho -T km hm (suppressor Tlymphocyte). Chng c th lm ngng li s lan truyn ca
mi giai on p ng min dch. Tht vy, thng xuyn vn
c s cn bng gia p ng min dch hiu qu v p ng
min dch c ch. Trong trng hp p ng km hm khn ;
thy c bt k mt hin tng min dch no c th phi liiii
c khi c s tip xc lp li vi mt khng niiyr-n. 'l'ruoiii
hp ny ngi ta gi l s dung np min (lcli (iiiimimc iol( 1
ance).
- Yu t' th hai l s iu ha i(li()l i|). 'riuii'il. IIK i(li()t.i|) (idios)
c ngha l c bit hoiic cVu Irc n;iy ciii
tlu' (lnli
ring cho vt ch v:i rlio tiil. lo.ii khii ntiiy'n. Mt kliMiir
th hon torm mi xuiYt, liin t.roii C(i tli biu Ui int kli n t
n g u v f ii in i

((')

i h i n ^ C|)il()| lKi i<(ii^ tif vi v ( r

nhn

16

khng nguyn ca n. Hnh thc iu ha ny lun sinh ra

mt p ng min dch kiu anti- idiotip iu chnh s p
ng trc . Do , kiu p ng anti- idiotip bn thn n li
l ngun gc cho mt p ng anti- idiotip tip theo v.v... T
, p ng min dch sinh ra mt chui cc hin tng
phc h: khng ch c s tng sinh ca nhiu dng t bo B v
T mang cc v tr tip nhn tng ng vi cc epitop khr
nhau ca mt khng nguyn cm ng m cn xut hin cc
dng t bo c ch v cc dng t bo kch thch bi cc mng
li idiotip. S iu ho min dch thc hin qua truMg gian t
bo cn lin quan n l thuyt la chn dng uc trnh by
tng qut hnh hnh 1.5 v 1.6
H thng m in dch cn ng v a i tr r't qitun trn g cho c th
trn quan im sinh l bnh. Min dch h c th c ng dng

trong cc lnh vc nghin cu min dch v bnh truyn nhim,

min dch v ung th, min dch v cy ghp, min dch v cc
bnh suy gim min dch mc phi AIDS, cc bnh t min
(autoimune disease).

17

K hng n gu yn

c> .r.\ ^ <j

A <1 V.

t o
i'
^ ____
T b^o trnh in
khng^y u y n

rT
w%
Cc t^ 1bo

- c che

T - hot ho
di thc bo

T - gy c

T - b tr

r t bo B

thc bcj

Khng th
_

- b o N K a ; g g T. gy c

T bo K
(DCC)

Cc t bo hiu qu

H n h 1.6 Con ng min ch qua trung gian t bo. Cc p ng

min dch qua tru n g gian t bo xy ra tip theo s trnh din khng
nguyn v s hot ho cc t bo T, c kim tra hng cc lympho T
c ch (suppressor T cell) v lympho T b tr (Helper T cell). Mt s t^
bo T (cc t bo hot ho di tlic bo) tit ra cc lymphokin hot ho
cc chc nng thc bo ca i thc bo v clit vi khun. Cc t bo T
gy c c ho t ho bn g k h n g nguyn r n g VI s g i ) ca C C
t bo b tr v hp tc tip theo vi cc t h B d sn xut khng
th . C c t b o K (Killer Cell) c t h t h m n g c i lc cao lin k t VI
m nh Fc ca cc l. bip^
khng th phn hu t
bo ^z\i U nhim khun, cn gi l ADCC (T bo gy c ph thuc
khng th: Antibody- dependcnt cell - mediated Cytotoxicity). Cc t
bao NK phn ng khng cn tnh c hiu. (Theo I. Roitt et al, 1993).

18

Khn

t bo B
S sinh sn v chin ca
t bo B c
la
chn

hng n;

A A A

T bo B

Cc khng th 2 dc sn xut
H n h l.5

Theo l thuyt la chn dng,

m i

t bo sn xut khng th

(t bo B) c t chng trn h tn g hp ch mt loi k h n g th

c m t di dn g mt th th nm trn b m t t bo ca n tng tc
c hiu vi mt k h n g nguyn. Sau khi tip xc vi khng nguyn, t
bo B c kch thch, sin h sn v s bit ha th n h cc t bo plasma
tng hp r a cc k h n g th. Mt s t bo B khc c hiu vi khng
nguyn cho, khng bit ho v s tr thnh cc t bo ghi nh min
dch, c i shg lu di. (Theo I. Roitt et al, 1993)

Hnh 1.3. Cc t bo
bch cu ca h min
dch bm sinh v min
dch tip thu.
T trn xung di;
1. i thc bo.
2. Bch cu trung tnh
3. Bch cu a axt.
4. Bch cu a kim,
5. Te bo mast,
6. T bo dit t nhin(NK).

Bch cu a kim

#
T bo mast

%'. _ a
t
5 #

bodittnhin(NK)

r'
^ S--

-4

t o

|> g

H n h 1 . 4 . C c t h o A P ( c h u y n n ^ l i } ).

T tri qua phi:

T bao x thy (dendritic cell), i thc bao (macrophage) va lympho B.
T trn xung di;
nh hin VI quang hoc (a, b, c); nh hin vi din t xuyn qua (d, e. f) va nh
hin vi in t qut (g, h,j).

19

Chng II. Khng nguyn

2.1. nh ngha v khi nim chung v khng nguyn

Thut ng khng nguyn (antigen, vit tt Ag) dng ch
mt cht c kh nng gy ra p ng min dch khi c a vo
c th ca mt ng vt thch hp hoc mt cht c kh nng
phan ng vi mt khng th hoc mt t bo ca h thng min
dch. Nh vy. tt c nhng cht t nhin hoc tng hp c h
thVig min dch nhn bit u c gi l cc khng nguyn.
Khi mt khng nguyn xm nhp vo c th, cc lympho c th
nhn bit c hiu bng cch kt hp vi khng nguyn nh th
th c hiu. S nhn bit ny gy cm ng sinh sn lympho-B
v bit ha qun th t bo ny thnh cc t bo plasma c kh
nng sn xut khng th chng li khng nguyn xm nhp.
l p ng min dch th dch. p ng min dch cng c th
gy ra s xut hin qun th lympho-T min dch mang cc th
th c hiu vi khng nguyn. l s p ng min dch qua
trung gian t bo.
Tnh phn ng ca khng nguyn hoc kh nng nhn bit,
kh nng liii kt o hiu ca khng nguyn vi khng th hoc
vi th th ca t bo ph thuc vo mt phn cu trc gii hn
ca khng nguyn. Phn cu trc gii hn ny c gi l quyt
nh khng nguyn (antigenic determinant) hay epitop. Cn phi
phn bit hai c tnh khc nhau ca cc epitop l tnh khng
nguyn (antigenecity) v tnh sinh min dch (immunogenecity).
ln h khng nguyn l c tnh ca mt epitop c cu trc ba
chiu lin kt b sung vi phn cu trc ba chiu ca phn t
khng th. Phn cu trc ny ca phn t khng th hoc ca
th th c gi l paratop. Tnh min dch ca mt epitop l c
tnh gy ra mt p ng min dch trong mt c th. Trong
trng hp khng nguyn l cc protein, ngi ta c th nhn

20

bit c kch thc ca mt epitop khng nguyn vo khong 5

n 10 gc axit amin bng phng php phn hy ha hc hoc
phn hy enzim i vi khng nguyn ny. Ngi ta cng phii
bit mt dng epitop th hai, gi l epitop gin on. Loi epitop
ny c xy dng t cc axit amin cch xa nhau theo trnh t
sp xp nhng li gn nhau v khng gian ca protein do s gp
li ca chui polipeptit.
S nhn bit gia khng nguyn v khng th ca n hoc
gia khng nguyn v cc th th ca t bo c thm quyn
min dch mang tnh c hiu rt cao. iu c ngha l mt
khng nguyn A ch c th c nhn bit bi mt khng th
anti-A hoc ch c th c nhn bit bi mt loi t bo lympho
c th th lin kt c hiu vi khng nguyn A.

2.2. Phn ng cho

Ngi ta ni phn ng cho khi mt khng th c kh nng
kt hp vi mt khng nguyn khc vi loi khng nguyn kch
thch s sn xut khng th ng vt gy min dch. Phn
ng ny c th do hai khng nguyn c mt hoc nhiu epitop
gihg nhau hoc mt s' epitop ca chng c th gn ging nhau
lin kt vi cng mt loi khng th. Chng hn mt epitop ca mt khng nguyn protein c mt chc gc axit amin
trong ch c mt hoc hai gc axit amin khc nhau th cu
trc ca cc epitop ni trn vn cn kh ging nhau cho mt
khng th nhn bit. Do , phn ng cho vn c th xy ra. C
th nu ra v d i vi cc khng nguyn c cha gc ng poliozit. Nhm mu A ca ngi c khng nguyn Naxetilgalactozamin, cn nhm mu B l galactoz. Trong nhng
hon cnh b nhim vi khun, khng nguyn Naxetilgalactozamin c th b phn hy, mt gc N-axetil chuyn
thnh galactozamin. Cht ny cng c nhn bit bi khng
th anti-B. Nh vy, khng th anti-B khng th phn bit c
s khc nhau gia galactoz v galactozamin.

21

2.3 Hapten v protein mang

C rt nhiu cht ha hc c phn t lng nh, phn cc
mnh c kh nng gy ra s tng hp mt khng th c hiu
sau khi c kt hp vi phn t mang c kch thc ln hn.
Cc cht ha hc ny c gi l hapten v c coi l tng
ng vi nhng quyt nh khng nguyn tch ri. Cc hapten
c kh nng phn ng vi cc khng th c hiu ca chng. Mt
quyt nh khng nguyn thuc v mt i phn t t nhin
trong khi mt hapten cn phi lin kt vi mt phn t bng mt
phn ng ha hc c th gy cm ng sn xut mt khng
th. gy ra mt phn ng min dch in vo, mt hapten cn
phi kt hp vi mt protein mang. V vy, ngi ta c th tng
hp nhng polipeptit nhn to c cu trc bit c th mang
mt hoc hai quyt nh khng nguyn. S kt hp ca hapten
v protein mang s to ra mt cu trc sinh min dch c t nh"t
hai quyt nh khng nguyn khc nhau.

2.4. Tnh khng nguyn ca cc cht sinh trng hp

(biopolymer)
c tnh khng nguyn ca mt cht c xc nh bng s c
mt hay vng mt ca tnh sinh min dch. Ngi ta phn bit ra
cc loi khng nguyn sau y:
- Autoantigen c mt chnh bn thn mt c th.
- Alloantigen c trng cho cc nhm c th trong cng mt
loi.
- Isoantigen c mt t"t c cc c th ca cng mt loi.
- Xenoantigen (heteroantigen) c mt cc c th ca nhng
loi khc nhau.
Cc cu trc cng khc nhau s cng biu hin tnh khng
nguyn r rt.
Protein: Hu nh tt c protein dng hnh si hoc hnh cu
u l nhng cht sinh min dch. Mc d protein l mt nhm
cht khng nguyn rt ln trong thin nhin, nhng do cu trc
v thnh phn ho hc ca chng rt phc tp nn vic hiu bit
cu trc khng nguyn ca cc protein cha c nhiu. Ch
trong mt s trng hp nh myoglobin, lyzozim v mt s' virus

22

(virus cm, virus vim ty xm polio) ngi ta mi bit r c s

cu trc khng nguyn ca chng mc phn t.
Cc polixacarit: y l nhm khng nguyn quan trng th
hai trong thin nhin v c trng ing phn t t mt n vi
triu dalton. Cc dextran, levan v mannan l nhng khng
nguyn c mt rt nhiu vi khun. c tnh khng nguyn ca
nhiu loi glycoprotein trc ht c biu hin bi phn cc gc
ng ca chng. Chng hn cc khng nguyn nhm mu ABO
ca ngi c trnh by di y:
1. Gal NAc (p 1,3) - Gal(p 1,3) - Glu NAc(p 1,3) - Gal(a 1,2)- Fuc.
= Khng nguyn H(0)
2. Khng nguyn H + (a 1,3) Gal NAc.
= Khng nguyn A
3. Khng nguyn H + (a 1,3)- Gal.
= Khng nguyn B
S cu

to cc khng nguyn nhm mu A, B, o

Cc lipit: Him khi ngi ta nhn thy s biu hin tnh

khng nguyii ca lip it nu n khng kt hp vi polixacarit v
protein. Cc diolipit cha photpholipit c mt thnh t" bo vi
khun hoc mng trong ca ti th t bo tim b cng c tnh
khng nguyn.
Cc axit nucleic: Kh c th nhn c s p ng min dch
chng li cc axit nucleic. Tuy nhin, trong huyt thanh ca
bnh nhn mc bnh t min, ngi ta thng tm thy cc
khng th c kh nng lin kt vi ADN hai chui hoc mt
chui lch ri, hoc ADN c gn vi histon.
Cc loi cht polipeptit v gluxit c tng hp nhn to
c s dng c kt qu nghin cu p ng min dch. Mt
s' thuc chit xut t thc vt hoc c tng hp cng gy ra
hin tng qu mn i vi ngi.
Cc siu khng nguyn (superantigens): Siu khng nguyn l
mt thut ng dng d ch cc phn t nhy cm c kh nng
lin kt vi cc phn t lp II ca MHC, ng thi lin kt vi
cc trnh t peptit c trng cho mt s h ca cc th th lympho-T (chng hn TCR-Vp). Cc siu khng nguyn ny hot ha
mt s ln cc dng t bo T (clon-T). Quan nim v siu khng
nguyn c th c m rng cho cc phn t c ngun gc t cc
vi khun c kh nng lin kt vi cc Ig mng t bo (mlg) v

23

hot ha cc lympho-B (v d cc protein A v protein G ca mt

s chng Staphylococcus).
Cc t cht (Aduvants): T cht l mt cht hoc mt hn hp
f;c cht c kh nng lm tng tnh min dch ca cc khng
nguyn, v ni chung thng gy ra cc phn ng vim. T cht
t,hng lm chm qu trnh loi b khng nguyn v to iu
kin cho vic bt gi v trnh din khng nguyn. T cht c
s dng thng xuyn l hydroxit nhm hoc cc ch't c ngun
gc vi khun. T cht khng y ca Freund l mt nh
ing c hnh thnh trong nc cng vi du khong v mt
I.c nhn gy nh tng (Tween). T cht y ca Preund l
t cht khng y cng vi cc vi khun lao b git (Mycohacterium tubercuosis).

2.5. S thch ng ca cc vi sinh vt bng cch ci

bin cc khng nguyn ca chng
Ngi ta cho rng ton b kho d tr cc peptit c nhn bit
bi cc lympho - T ca mt c th, ph thuc vo cu trc ca cc
phn t ca MHC v ph thuc vo c ch dung np vi cc
peptit ca bn thn khi c s bit ha ca cc lympho - T. Nu
mt lym pho - T ca h thng min dch c phn ng chng li cc
thnh phn ca bn thn th s a n tnh trng bnh t
m in. Trong qu trnh pht trin ca h thng min dch, khi cc
t bo T nhn bit thnh phn ca bn thn c th gy ra phn
ng khng th lp tc qun th t bo T b loi b bi
chnh h thng min dch.
Cc vi sinh vt c th s dng nhng chin lc khc nhau
tu thot khi s nhn bit ca vt ch bng cch ci bin cc
peptit khng nguyn ca mnh. Chng c th bt chc cc cu
trc peptit ca c th vt ch. Nhng s ci bin ny ch c
xut hin nu vi sinh vt sng lu di trong vt ch. l
trng hp ca bnh nhim trng mn tnh. Cng tng t nh
vy, cc t bo ung th c th b ph hy bi h thng min dch
v chng hon ton khc l vi cc t bo bnh thng ca c th.
Tuy nhin trong mt s trng hp cc t bo ung th c th t
ci bin khng nguyn ca chng trn thot khi s ph hy

24
ca h th n g m in dch.
di cn.

l trng hp u n g th tin trin ho(C

2.6. Immunogen v kh nng p ng m in dch

Immunogen l mt khng nguyn c c hai tnh cht: tnh
khng nguyn v tnh sinh min dch. Tnh khng nguyn C
biu hin bng cc epitop c nhn dng v lin kt vi khng
th hoc vi th th ca khng nguyn. Tnh sinh min dch biu
hin kh nng p ng min dch to ra khng th hoc to
ra s p ng min dch qua trung gian t bo. Mt s cht C(
tnh khng nguyn nhng kch thc li qu nh khng th C(
kh nng to ra p ng min dch. V d, 2,4D l mt cht kch
thch sinh trng cng c mt trong thuc tr su c kh lrig
phn t rt nh khng th to ra c khng th khi gy mim
dch. Mt vi peptit c phn t lng nh hn 3.000Da cng hiii
nh khng to ra kh nng sinh khng th khi gy min dch..
Tuy nhin nhng cht trn khi kt hp vi cc protein marig
(Carrier protein) s c kh nng trd thnh immunogen v d p
ng min dch to khng th.

25

Tm tt chng II

1. Mt phn t c coi l khng nguyn nu c kh nng lin

kt vi cc th th ca lynipho T. lympho B hoc vi khng
th. c tnh ny c xc nh bng nhng s khc nhau v
cu trc b sung gia khng nguyn v th th ca t bo T.
t bo B (TCR, BCR) h o c paratop ca khng th c th c
gy min dch.
2. Phn t irotein c cc quyt nh khng nguyn (epitop)
dng khm khc nhau nhng c khi dng cc epitop lp li.
Cc epitop thng c trnh t cc axit amin lin tc, cng c
th gin on nhng gn nhau v khng gian.
3. Hapten l nhng cht ho hc c phn t nh, c kh nng gy
ra s tn g hp k h n g th c h iu vi n kh i c k t hp vi

mt phn t cht mang c kch thc ln hn. Hapten khng

ph i l k h n g n gu yn hon chnh nh ng c th c coi tng
dng vcii n h n g epitop tch ri.
4. Cc hp cht sinh trng hp (biopolymers) nh protein. polix-

acirit, lipit, axit nucleic v.v... c c tnh khng nguyn khc

n h au v c tn h sin h m in dch khc nhau. T ro n g s cc hp

cht k trn, protein v polixaoarit l 2 nhm khng nguyn

ln v quan trng nht.
5. Cc vi sinh vl va cc L bo ung th c th s dng nhng
cch khc nhau d trn thot khi s nhn bit ca h cc t
bo min dch vt Ch bng cch t Cii bin cc khng nguyn

ca mnh.

27

Chng III. Cc khng th v th th ca khng nguyn

Cc phn t tham gia p ng min dch c hiu bao gm cc

khng th cn gi l globulin min dch (Immunoglobulins, vit
t t Ig) c h a tan trong cc dch sin h v t hoc h n h th n h nn
cc th th trn mng t bo lympho-B (B cell receptor: BCR) v
cc th th ca lympho-T (T cell receptor; TCR). Cc phn t
khng th c bn cht l glycoprotein, m bo cho vic nhn
bit cc epitop ca khng nguyn bng v tr b sung khng gian
c mt trong phn t ca chng. V tr lin kt b sung ca phn
t khng th i vi khng nguyn c gi l paratop c cu
trc rt a dng. Ngi ta tnh c rng mt c th trng
thnh c khong 10' phn t Ig trong c trn 10 loi phn t
khc nhau v trn 10^ cc dng IVmpho-T khc nhau.
Cc Ig l nhng phn t hai chc nng. Phn N tn cng ca
phn t c mang v tr paratop m bo cho vic nhn bit c
hiu khng nguyn. Phn c tn cng khi ng cc tn hiu sinh
hc c c l do s lin kt gia paratop v epitop.
Cc chui polipeptit ca cc Ig, TCR, BCR u c hnh
thnh t cc tiu n v dng hnh cu (subunits) c cu trc bn
chc to ra cc khu vc (domain) gm khong 100 axit amin v
mt cu disunphua. Cc tiu n v nh trn c gi l cc khu
vc chc nng (domain). Cu trc c s nh vy c tm thy
{t c cc protein thuc v siu h (superfamily) ca cc immunoglobulin. Siu h ny bao gm mt tng th cc phn t protein mng tham gia vo s tng tc gia cc t bo, c bit l
cc phn t ca MHC (hoc HLA ca ngi).

3.1. Cu trc chung ca cc immunoglobulin(Ig)

Cc phn t Ig c hnh thnh t hai loi chui polipeptit l
ohui nng (k hiu l H: heavy chain) v chui nh (k hiu l L:
light chain). Cc chui nng thuc v cc dng s, yl, 2, 3, 4,

28

a l, a2, e. Cc 'chui nh bao gm hai dng K, X. Kiu chui nng

xc nh n v phn loi lp v cli lp (class, subclass) ca cc
Ig. T d khng th bao gm 5 lp l IgM, IgD, IgG, IgA v Ig]C
v cc di lp IgGl, IgG2, IgG3, IgG4, IgAl, lgA2. Cc phn t
Ig c cu trc i xng c th k hiu (H2, k2) hoc (H2, X2).
Con s n c th l 1 (i vi IgM mng, IgD, IgE, IgA dng
mono), l 2, 3 hoc 4 (i vi IgA dime, trime, tetrame). hoc
(i vi IgM pentame). Cc Ig polime (IgM, IgA) cn cha chui J
ni cc u c tn cng ca cc chui H. Cc chui L (Kappa: K v
lambda: X) u c hnh thnh t hai vng khu vc l: khu vc
d bin i (Vk hoc vx.) v khu vc khng i (Ck hoc CX). ('c
chui H gm mt khu vc N tn cng d bin i (V||) v 3 khu
vc khng bin i (l vi IgD, IgG v IgA) hoc 4 khu vc
khng bin i (i vi IgM v IgE). Khu vc khng bin i (;a
chui nng c k hiu l C||. Mi mt khu vc d bin i u
bao gm 3 vng siu bin (hypervariable), cn gi l cc vng xc
nh tnh b sung (CDR). Cc paratop c hnh thnh t nhng
v tr t k nhau trong khong khng ca cc vng siu bin
c tch b it nh au bng hai v n g bo th hn (hoc cc v n g

khun). Vng nm gia hai khu vc Cil v C2 ca chui H

c gi l vng khp hay vng bn l m bo cho tnh mm
do ca cc phn t khng th, ng thi hai cnh tay (V|,, C|,,
V||, Cnl) ca phn t c th di ng trong khng gian. Cc vng
nm gia cc khu vc c th c phn gii bng cc proteaza
nh papain, pepxin (hnh 3.7). Papain phn gii IgG to nn hai
mnh Fab (L+Vj|+C||l) v mt mnh Fc (dime ca cc khu vc
C|i2+ Ch3). Thut ng Fab dng ch mnh lin kt vi khng
nguyn (antigen binding) v mnh Fc l mnh d kt tinh
(cristallisable). Pepxin phn hy IgG to thnh hai mnh F(ab>2
v cc peptit pFc. Cc mnh Fab v Fv (Vl+V||) cha ng cc
paratop, trong khi cc phn Fc m bo cho nhng c tnh
gy hiu qu ch yu ca phn t khng th v khc nhau ty
theo cc lp v cc di lp ca cc Ig. S khc nhau th hin
t l bin i trong trao i cht, s vn chuyn qua nhau thai,
s vn chuyn qua cc t bo biu m bng cch lin kt vi mt
th th poli-Ig, kh nng hot ha b th v lin kt vi mng
t bo.
S lin kt gia khng nguyn v khng th c th gy ra ha i
hiu qu:
1. Hot ha h thng b th.

29

2. Hot ha cc t bo khc nhau c cc th th - Fc nm trong

mng t bo ca chng.
S hot ha b th theo con ng c in (con ng ca b
th Clq) b gii hn mt s' lp v di lp nh IgM, IgGi, IgGa
v mt phn nh cc IgG. S biu hin ca cc th th-Fc khc
bit nhau tu theo cc kiu t bo nh t bo mast, lympho, i
thc bo, t bo a nhn trung tnh, t bo tiu cu V.V.. T
gy ra vic s n xu t cc lp v cc di lp Ig sa u khi gy m in

dch vi mt khng nguyn, ko theo nhng hiu qu sinh hc

khc nhau ty thuc vo cc m t bo. S lin kt ca cc Ig vo
cc th th - Fc c th gy ra nhng tn hiu hot ha cc t bo
nh: hiu qu gy c ca cc lympho-T, kh nng thc bo ca
cc i thc bo v ca cc t bo a nhn trung tnh, gy hiu
qu loi b cc ht ca cc t bo mast v t bo tiu cu.
Cc chui nng ca Ig lun lun c kt hp vi cc gc
cing cc v tr khc nhau. Nhn chung, cc gc ng kt hp
vi Ig l cc oligoxacarit c cha mt hoc nhiu gc axit sialic.
cng mt chui nng c th c s khc nhau v kiu kt hp vi
cc gc ng, t s to ra mc b sung cho tnh cht khc
bit phn t ca cc Ig. Chng hn, cu trc ng ca IgG khc
vi IgA v IgD, hn na cu trc ng ca di lp IgA khc
vi IgA2. Thm vo , s thay i bt thng ca cc gc ng
kt hp vo Ig s gy ra mt s bnh t min (autoimmune
diease).
Ni chung, cc phn t Ig tng i bn nhit ( 56C trong 30
])ht), ngoi tr IgE km bn nhit v b ph hy trong nhng
(tiu kin ny.
Cc lp v di lp Ig c phn b khc nhau cc dch sinh
vt. Cc IgM ch yu c tm thy khu vc trong cc mao
mch. Cc lp IgG phn b ng u cc phn mao mch v
ngoi mao mch. Cc IgA ca huyt tng ch yu c sn xut
t cc t bo plasma dng IgA ca ty xng, trong IgA
monome chim ti 90%. Cc Ig c tit ra t rut ch yu bao
gm cc IgA tit dime hoc polime v c t l tng ng gia
IgA| v IgA,. Ngoi ra, ngi ta cn tm thy mt lng nh IgM
tit. Cc Ig tit c sn xut t cc t bo plasma ca m lin
kt nm tip xc vi biu m nhy c cha cc th th poli-Ig c
nh cc Ig polime. Phc h Ig-th th poli-Ig di chuyn v pha
mng ca t bo biu m. , th th poli-Ig s b phn tch ra
thnh cc Ig tit (IgM hoc IgA polime) v chng s c kt hp

30

cng ho tr vi mt thnh phn tit. Cc IgA ch yu c tit

t nc mt, nc bt, cc dch mi hng trong mt, trong sa,
trong dch tit ca rut, ng sinh dc v mt s" tuyn nhy
(nim mc: mucosal).
S vn chuyn qua nhau thai ca cc khng th c bit lin
quan n 4 loi di lp IgG. S vn chuyn ny t ti cc i
cui thi k c mang v nng Ig ca mu thai nhi lc bng
vi nng Ig trong mu ngi m. S chuyn ha cc IgG trong
c th ca tr s sinh s c thc hin bng cch gim dn dn
nng Ig ca huyt thanh v chuyn sang mt thi k h thp
gamaglobulin sinh l gia thng th t v thng th su ca tr.
C th thai nhi cng tng hp dn dn cc loi Ig ring bit,
trc tin l IgM, sau n IgG v cui cng l IgA. S c mt
ca cc khng th c hiu ca lp IgM v IgA trong mu ca
cung n h a u th a i cho th y cc k h n g th ny c t n g hp bi
h thng min dch ca bo thai. Du hiu c th c s
d ng ch n on s nh im tr n g ca bo th a i bi cc v iru s.
Domain

Vng
lin kt
khng
nguyn

o .o > ,

C2 c3
IgG IgGa v IgG

Hnh 3.1 Cu trc chung ca phn t IgG. Cc vng N tn cng ca

chui nng (H) v chui nh (L) c trng cho cc trnh t d bin i
(V) c gi l cc vng Vh v v^. Phn cn li ca phn t c cu trc
tng i n nh. Phn khng i ca chui nh v chui nng tng
ng c gi l Cl v Ch, tuy nhin phn khng bin i ca chui nng
bao gm 3 khu vc khc nhau l ChI, Ch2 v Ch3. Cc khu vc ny (domain) c dng hnh cu v c n nh bng cc cu disunfua. Hai v

tr lin kt vi khng nguyn nm cc khu vc d bin i. Vng khp

hoc vng bn l ca chui nng nm v tr gia ChI v Ch2 c c

tnh kh mm do cho php thay i khong cch gia hai v tr lin

kt gia khng th v khng nguyn, ng thi cng m bo cho s
tng tc c lp ca cc khng th i vi khng nguyn. Cc chui
polixacarit c gn vi khu vc Ch2.

31

Chui J

Hnh 3.2

C u t r c p e n t a m e c a p h n t I g M

c a n g i. C c c h u i

n n g c a I g M c 4 k h u v c v n g k h n g b i n i c a c h u i n n g . C c
n v k h c n h a u c li n k t v i n h a u b n g n h n g c u d i s u n f u a g i a
c c k h u v c C ( i 3 v C f i4 k c n . C c c h u i o lig o x a c a r it c n g n m c c
v t r c a c h u i n n g c n g ' n h n m m t v t r g i t h i t c a m t c h u i
J . ( T h e o I . R o i t t e t a l. , 1 9 9 4 )

3.2. Cu trc phn t ca cc immunogobuin ring bit

TgG: IgG l mt globulin m in dch c s lng ln nht trong
huyt thanh ca ngi. Nng trung bnh trong huyt thanh
ca ngi kho trng thnh l t 10 n 14g/lt. Phn t IgG c
3 k h u vc v n g k h n g i ca chui n n g l ChI, Ch2, Ch3. IgG

dng monome v bao gm 4 di lp (lp ph) l IgGj, IgGa,

IgG;,, IgG^. N g i ta bit, IgG 2 c s n x u t c u t h p

ng li vi cc polixacarit ca vi khun. Cc IgG l mt trong

n h n g c h t h o t ho ch yu ca con ng h o t ho b th th eo

kiu c in. Cc th th Fcy c vai tr quan trng i vi s vn

chuyn IgG qua mng nhau thai t ngi m n thai nhi. iu
n y c vai tr q u a n trng vi tr s sin h kh i h th n g m in
dclh kh i h th h g m in dch ca tr cha ch n m i.

32

IgM: IgM c cu trc l dng pentame trn c s c hnli

thnh t mt n v bao gm 2 chui nng ^ v 2 chui nh. Cc
chui |i khc vi chui Y trnh t cc axit am in v s lng co
khu vc khng bin i. C 4 domain vng khng bin i ert
chui nng nm di n v ca IgM c lin kt vi nhau bng
cc cu disunfua gia cc khu vc C^i3. IgM thng c gi l cc
macroglobulin min dch v c khi lng phn t rt ln. S
polyme ho cc monome ca IgM ph thuc vo s c mt ca
chui ni J (Joint). Chc nng ca chui J l lm n nh cc
nhm SH (sunohydril) ca cc vng FC hnh thnh cc eu
disunfua (S-S) cn thit cho cu trc pentame (hnh 3.2). Nng
trung bnh ca IgM trong huyt thanh ngi t 0,5g n 2,5g/lt.
IgA : Cc IgA xut hin c chn lc trong qu trnh tit ca cc
tuyn nhy nh tuyn nc bt, tuyn l, tuyn m hi, tuyn mi
hng, tuyn sa, dch nhy c quan sinh dc, tit niu v cc
tuyn tiu ho d dy v rut. iu chng t IgA c vai tr
ngn chn s xm nhp ca cc vi sinh vt vo cc c quan ni
trn. IgA tun hon thng dng dime ngn nga s phn
hu ca cc proteinaz nh phn t ca n c mt mnh tit (mnh
S) lin kt 2 monome vi nhau. Mnh tit c phn t lng 60
kDa, v c tng hp ti ch cc t bo biu m. Cc IgA dime
khi c tng hp ti ch t cc t bo plasma c thm mt peptit
ni (peptit J) rt giu xistein v c khi lng 15 kDa. Chc nng
ca IgA l km hm s hot ng ca cc vi sinh vt b kt
dnh trn b mt ca cc t bo tuyn nhy v dng thi ngn cn
s xm nhp ca chng vo cc m. Cc IgA kt t s c c nh
ln cc t bo a nhn v hot ho b th theo con ing lun
phin nhau. c tnh ny ph hp vi cc dn liu chng m inh
cho s hip ng tc dng gia IgA, b th v lyzozim trong qu
trnh ph hu m t s dn g vi sin h vt. H u yt tng ca ngi

bnh thng c cha mt lng IgA monome nng khong

2,5-3 mg/ml (hnh 3.3 v 3.4).
IgD: IgD ch c mt mt lng rt t (khong 1%) so vi cc Ig
khc ca huyt thanh. Khng th ny rt nhy cm i vi tc
ng ca proteaz, v c khuynh hng t phn hu nhanh. Trong
phn t IgD c m t cu disun fu a lin k t gia 2 chui n n g s v

lin kt vi nhiu chui oligoxacarit, trong c mt chui giu

loi ng N-axetilgalactozamin. y l mt loi ng cng c
mt trong phn t IgAi nhng khng c bt k loi Ig no khc

33
(h h

3 . 5 ). N n ^ cl I g l ) t r o n g l u y t t h a n h

k h o n g t 0 , 0 4 m ^

n g i k h e r^t t h p

0 ,0 r )m g /m l

H n h 3 . 3 Cu tr c IgAj ca ngii. S ny cho bit cc

cu d i s u n u a gia cc chui n n g v chui nh, gia cc

chui n n g vi n h a u v trong cc chui n n g hoc trong cc
clui nh. xMt cu d is u n u a b s un g lm n n h k h u vc
C a2 v mt cu dis unfa lin kt chui fj trong IgA polime.

H n h 3.4 C u tr c IgA tit (slgA) c a ngi. l mt

IgA d im e iic t<7() hi 2 di dn v IgA n

chui J v m n h tit s.

VI

nhau bng

34

Cc gc n g

Domain

M u u i

H n h 3.5 ( 'u tr c gl) ca ngi. S n y ch r cc cau

d i s u n u a gia cc cliui p o li pe pt il v t r o n g cc chui,

dng lli ch r v Ir gia thi t c a cc chui oligoxacarit.

H n h 3 . 6 c "u tr c IgE c a ngi. S ch r 4 k h u vc

k h n g bic n i, cc cu d i s u n u a gia cc chui v t r o n g

cc chui, v tr cc chui polixacarnt.

35

F(ab>2
\

.... . . C

Cc peptit nh

pFc

' c r
CLH.I \ \ J ^

PEPXIN

_
PAPAIN

V tr ct th c'p ca
pVpain

Fc
Fab

Hinh 3.7 S thu phn bng cc proteinaz i vi IgG, ca ngi.

Pepxin ct IgGj thnh cc mnh F(ab')2 v mnh F(c') v cc mnh
peptit c phn t nh. Trong khi papain phn gii IgGi v tr
gc 224 ca vng khp v gii phng 2 mnh Fab v mt mnh Fc.
im ct sau v tr 341 ca mnh Fc s to ra cc mnh Fc'.

IgE: Nng IgE trong huyt thanh rt thp nh hn 0,3mg/l

nhng trnh t axt amin c sng t nh cc IgE n dng
ca u tu c tinh ch. Chui nng 8 c khi lng kh cao l
72,5 kDa gm 550 axt amin v phn chia thnh 4 khu vc
khng bin i l Cel, Ce2, Ce3 v Ce4. Mnh Fc ca IgE cha
ng mt phn ln cc epitop c hiu ca phn t v lin kt
vi b mt t bo mast (mastocyte). Mnh Fc cng c cc quyt
nh khng nguyn. IgE thng tham gia vo cc phn^ng
vim, phn ng d ng v hin tng qu mn (hnh 3.6). C th
tng kt mt s tnh cht ca cc lp Ig ngi theo bng 3.1

36

Bng 3.1. Mt s' c tnh c bn ca cc Im m u n oglob u lin ca

ngi
1

___

_______

CcTccI Allotyp

I Kh

Ig I lp ca

I lng

'

ph I chui
nng

phn t

Nng !
trong
huyt
thanh,
mg/100 ml

Chc nng sinh hc

_________________________________4 ------------------

IgG

IgG
_
IgG^,
Ig o ;

1_

800-1700 Nhn bit virus,

khun, c t"

vi ^

Hot ho b th

IgG,

Lin kt vi th th Fcy
Qua mng nhau thai
Khng 970, dng 0 ^ 5 0 - 2 5 0
pentame V : 60-270
Dng
monome
trong
Ibnh
u

IgM

Xut hin u tin saU

kh i kch thch Ag.
;
Ngng k t hng cu
khun, virus.

V)

Lin kt vi Ag, hot ho:

b th.

_____ ____ ______

gA,

IgA

IgA;

i
1

IgD

0^100 400 Chng li vi khun, virus,

nguyn sinh ng vt
320, dng
nh c mt tuyn nhy.
dime
trong IgA
Hot ho b th theo con^
tit v c
ng xen k.
dng
Tham gia vo opsonin ho;
tetrame
khi phn ng vi th th

Khng 160

Fca
khng

175

< 10

Ch yu tm thy t bo
B, c th khi tip xc VI
Ag, truyn tn hiu hoat
h o t b o B
;

khng

190

< 0 ,0 3

Tham gia phn ng viiTi

d ng, qu mn khi lin
kt vi t bo mast
'
1

Ig E
1

37

3.3. M i quan h gia cu tr c v chc nng ca cc

khng th
Chc nng u tin ca cc khng th l lin kt vi khng
nguyn c hiu vi chng, tham gia vo cc p ng min dch
dch th (trung ho cc c t vi khun v virus), p ng min
dch trung gian t bo (tham gia hin tng opsonin ho, to
iu kin bt gi v tiu ho khng nguyn, vi khun v.v...). S
hot ho b th l c ch c hiu qu quan trng nht ca cc
IgG, v IgG;,. H thng b th l mt nhm cc phc h protein
huyt thanh tham gia vo phn ng vim. Sau khi lin kt vi
khng nguyn, cc IgM, IgG, IgG.i c th hot ho mt dy cc
enzim ca b th. Trong khi cc IgGa t c hiu qu ny. Cc
IgG IgA, IgD v IgE khng c kh nng hot ho b th.
ngi tt c cc IgG u vt qua hng ro nhau thai n
vi tr s sinh v thc hin chc nng min dch th ng. Cc
ng vt khc khng c kh nng ny tuy nhin sau khi sinh IgG
ca sa m s c tru yn cho c th ng v t con mi sin h qua

ng tiu ho. Cc nghin cu v cu trc ca cc khu vc chc

nn g v cc di n v chc n n g ca cc Ig cho th y mi m t
n v cu trc l k t qu ca s tin ho rin g b it th eo chc

nng c hiu. Chng hn cc vng d bin i Vh, V|, l vng

lin k t vi k h n g nguyn, cn cc k h u vc khc tr th cho cc

chc nng sinh hc ca khng th. Ngi ta cng bit rng cc

di n v Clq ca b th tng tc vi khu vc Cy2 (IgG) v
m t v tr k im tra s trao i ch t ca cc phn t Ig nm cng

mt khu vc. Nhng tng tc i vi cc i thc bo v t bo

mono c c l nh v tr khu vc Cy3. Cc v tr g ln nhau
cua 2 khu vc mnh Fc c th l Cy2 v Cy3 c hiu qu hip
ng tham gia tng tc vi cc th th ca cc t bo.

3.4. C s di truyn v tnh a dng ca khng th

Theo l thuyt la chn dng ca Jerne v Burnet, Dreyer v
Bennett t c s khoa hc gii thch tnh a dng cu trc
ca cc khng th. C 3 c ch cho php h thng min dch sn
xut ra cc vng d bin i V ca chui nng v chui nh cc
mc khc nhau:

38

1. C nhiu gen nh (minigen) tn ti cc vng khc nhau c:i

nhn t bo vi s lng r"t ln m ho cho mi mt khu vi:
ca chui nng v chui nh. Tnh a dng ca cc Ig cho ph)
biu hin trn 10* cc idiotyp khc nhau, do d ti t hp e:i
cc minigen.
2. S t bin soma: Mt gen V nguyn gc c th b t bin trong
qu trnh pht trin c th (ontogenesis) ca mt t bo B.
3. S ti t hp soma: Mt s lng no cc mnh gen (t Ji
n J) c t hp li v nm bn cnh mnh gen m ho cho
phn ch yu ca vng V. iu c hnh thnh trong qu
trnh pht trin c th ca t bo B v t ti tng hp mt
protein c ch a cc trnh t c m ho bi cc m nh en

khc nhau.
C 3 c ch trn u c hiu qu hip ng gii thch tnh a
dng ca cc khng th. Trong nhng nm gn y nh cc tin
b trong nghin cu sinh hc phn t ngi ta bit cc loi
protein ca sin h v t bc cao ( u cariota) c m ho b n g n h iu

exon ring bit cch ri nhau bng nhng on intron km hm

qu trnh tng hp. Cc on intron ny s b loi b bng s
chuyn on (translocation) ca ADN hoc bng cch ct b cc
mnh tng ng trn phn t mARN. Mt gen c phn chia
thnh cc phn: trnh t dn L cn cho s vn chuyn gen qua
li ni cht, mt mnh VA. m ho cho cc axit amin (c th t 1
n 98 i vi mnh v x ca chut), mt mnh gen ni J m ho
cho 11 axit amin sau cng ca vng d bin i, v mt mnh
gen cx. m ho cho vng khng bin i. Khi lympho B chn v
bit ho thnh t bo plasma tng hp chui X th phn t
ADN s t sp xp sao cho cc mnh L, vx v J gn nhau (Hnh
3.8). Tuy nhin mnh gen CA. vn cn cch bit vi mnh J bng
mt on intron khong 1250 nucleotit. S lp rp li cc mnh
gen L, vx., J v cx trong phn t mARN s cho php to ra kh
nng tng hp chui nh X lin tc.
Nguyn tc nh trn cng c p dng cho s tng hp chui
nng H v chui nh K, mc d cc mnh gen trng hp ny
ln hn rt nhiu so vi chui, X. Ngi ta tm ra trn 200 gen
V k v ch ia th n h 5 h kh c n hau, m i chn g cha cc gen c

quan h thn thuc vi nhau. Mc d cc gen ca cng mt h c

mt s khc bit vng khng bin i v vng siu bin nhng
nhn chung kh gihg nhau. C 5 gen J khc nhau trong ch

39

c 1 gen m ho cho vng khng bin i ca chui K (hnh 3.8,

3.9,3.10)
Mt dy cc gen m ho cho cc chui nng c c tnh l tt
c chng u m ho cho vng khng bin i ca mi di lp
v c tp hp li thnh mt nhm gen. Mt nhm ny bao gm
12 mnh gen D c c tnh d bin i v c ci xen gia cc
vng gen V v J. S t hp cc mnh gen D v J s m ho cho
vng siu bin th ba (ton b vng siu bin bao gm ba phn),
cn hai vng siu bin th nht v th hai s c m ho bng
trnh t ca mnh gen V.
Ngi ta phn bit ba kiu khc bit cn c vo cu trc phn
t ca cc khng th. chnh l nhng mc khc nhau ca
cc epitop nh khu trn phn t Ig. T tnh a dng ca Ig
c biu hin ba mc sau y:
VKhc hit izotip (Isotype variation): Cc gen ca khc bit izotip c mt tt c cc c th cng mt loi ng vt sn
xut ra cc chui nng ( i, 6, Y, e, a ) v cc chui nh ( K, X ),

l trnh t c bn ca cc vng V ca cc di lp.

2 )K h c h it a llo tip (a llo typ e va ra tio n ): K hc b i t n y bao gm s

khc nhau v gen trong cng mt loi ng vt v s

dng nhng alen khc ca cng mt locus. Mt allotip
khng c tm thy tt c cc thnh vin ca mt loi.
Chng hn allotip G3m (bo) ca IgG3 c trng cho mt gc
phenylalanin v tr 436 ca chui nng khng phi c tt
c cc c th ca cng mt loi. Cc khc bit allotip thng
xuyn nm cc vng khng bin i ca chui nng. n nay
ngi ta pht hin c 25 nhm quyt nh allotyp trn
chui nng gamma ca IgG, c gi l ch th Gm (Gamma
marker) v 2 quyt nh allotyp trn chui a l IgAml) v
IgA2(m2 ). Ngoi ra vng khng bin i ca chui nh Kappa
cng biu hin allotyp Km(l), Km(l,2) v Km(3).
3)
Khc bit Idiotip (Idiotype variation): nhng khc bit nm
khu vc d bin i c bit cc vng siu bin. Ni chung
mt idiotip c hiu cho ch mt clon t bo sn xut ra khng
th, to ra mt id io tip c th. Tuy nhin ngi ta cng tm
thy cc clon khc nhau c th biu hin cng mt idiotip. Cc
idiotip ny c gi l idiotip cng cng hay idiotip hi quy.
Mi s kin ti t hp cc vng gen bin i xy ra u do s
ct gt v ti t hp i km to thnh trnh t gen gm cc
vng gen L (gen dn), gen V (gen bin i) v gen J (gen n) xch

40

li gn nhau, c chc nng. Tham gia vo qu trnh ny c cc

enzym thuc phc h Recombinase V(D)J trong c cha ccprotein RAG 1 v RAG 2 (sn phm ca cc gen hot ng ti t (
hp - Recombination activating genes), ligase IV, Proteinkinase'
ph thuc ADN (DNA-PK), protein Ku (l heterodime Ku 70. Kui
80) kt hp vi DNA PK. Mt s protein trn c hot ng oxonuclease v endonuclease.

L ocu s ch u i n h X
v >.1

li v\2

_ LVi,*29

Cil

L ocu s ch u o n h e K
l'

Vv^

12

v 2

13 V..3

L v>40 ,

Jvl-5

L ocu s ch u o i n n g
1.' V m I

12

L3 Vm 3

D m 1-27

J h 1-6

H n h 3.8: S s t chc cc locus gen ca ca chui n h X, K v

chui nng ca khng th ngi
Locus gen chui nh X nhim sc th 22 c khong 30 m n h gen v>
c chc nng, 4 cp gen
v cc gen c x
Locus gen chui nh K nhim sc th 2 c t chc tng t, c 40
gen V k i km vdi 5 J k nhng ch c 1 gen C k *
Locus gen chi nng nhim sc th 14 c khong 65 gen V|, 27
gen D v 6 gen J|j v cha hng lot cc gen c khc nhau, L l gen m
ho cc trn h t dn u ca cc gen (Theo Ja n ew ay C.A. e t , al, 2001)

Chui nh

AND mm

Chui nng

lt hp soma

ADN ni D-J

Ti t hp soma

ADN ni VDJ
sp xp li
L

V DJ

Phin m

AA

Bn phin m
u tin ARN

t V DJL
AAA

ct ni

m ARN

Phin dch
Cc chui
polypeptit ca ig

Hnh 3.9: ( 'c :vn v n ^ l)in i dc to ra t cc n i n h

h n h t h n h tih c diiK ca k h a n g t h

H n h 3.10: C( ch ti t hp cc mnh

() vn.i>: hin i ca \X

1. A X l ) m n i .
2. C ch to vng cho ct ni cc mnh ^en.
3. C( ch loi h() cc mnh intron v exon klc.
1. Lap ^ip cc mnh ^en ph h]) ( hot tnh cho vn^ hin i

41

Chuonng
L

ADN mm

-B-

Tl t hp soma

i a

_ _ _ _ _ _ _ _ _ _ _ _____ _

ADN ni D-J

Ti t hp soma

V J

ADN

ni VDJ sp xp

lai

I 0J

_____ _____ ,

Phin m

A.AA

n phin m u
in ARN

V J

L V CJ__ _ _ _ _ _ _

Ct ni

m ARN

Phin dch

1
/c chui

potypeptil

;a Ig

H n h 3.9: Cc gen v n g bin di c t o ra t cc

m n h gen h n h t h n h t n h da d n g c a k h n g t h

42

1.

L, V,

l i V

..... 0 h " T

2.

3.

4.

Hnh 3.10; C ch ti t hdp cc mnh gen vng bin i ca Ig

1. ADN mm.
2.

C ch* to vng cho ct n cc mnh gen.

3. C ch loi b cc mnh intron v exon khc.

4. Lp gip cc mnh gen ph hp c hot tnh cho vng bin
i

43

3.5. Cc khng th n dng (monoclonal antbodies)

S p ng min dch tng hp khng th xy ra rt tinh vi;
mi epitop s c h min dch sn xut ra mt loi khng th
c hiu. Sau khi gy min dch vi mt khng nguyn ngi ta
s nhn c cc khng th c hiu, c cu trc rt khc nhau
bi v mi mt t bo B ch sn xut ra mt loi phn t th th
BCR v t ch c th tit ra mt loi khng th. Trong khi
mt phn t khng nguyn c th cha nhiu epitop khc nhau.
Ngi ta c th lm bt t mt dng t bo B bng cch lai soma
vi mt t bo ung th (dng u tu khng tit khng th). Bng
cch to dng (cloning) lai soma, c th nhn c th lai (hybridoma) sn xut ra ch mt loi phn t khng th. Cc khng
th ny c gi l khng th n dng, c cu trc phn t hon
ton ging nhau v c s dng rt a dng trong phn tch
sinh hc v cha bnh. S phng php sn xut khng th
n dng c trnh by hnh 3.11.
Trong mt s' dng bnh l ca ngi nh cc bnh u tu (myeloma), ung th bch cu c tnh dng (leukemia) tin B, bnh
Waldenstrom, qu trnh tng sinh n dng ca mt dng t bo
B thng xy ra s to ra cc khng th n dng. Cc khng th
n dng ny c th c pht hin trong huyt thanh hoc nc
tiu ngi bnh bng phng php in di min dch hoc k
thut ELISa !

44

lym pho B

KHNG NGUYN

jj
.21

^ > 2

TB u tu

dung
hp

___
t<= i
^

w^

Huyt thanh

1,*.

U2-3J '*

khng th i "
a dong ^

i
3^

l
;

S ct

3;
k

2,
-.''

to dng
lai
th lai
clon

3
<4
; khng th

n dng

Hnh 3.11: S sn xut khng th n dng (tng kt phng php

ca Kohler v Milstein, Nature 1975, 256: 495-497). Mt chut nht
c gy min dch vi mt khng nguyn mang cc epitop khc nhau.
Huyt thanh min dch cha cc khng th a dng (polyclonal antibodies),' khc nhau v nhn bit cc epitop khc nhau ca khng
nguyn. Mi t bo B ch sn xut ra mt loi khng th s c dung
hp bng cch lai soma vi cc t bo u tu (khng tit khng tht

nhng bt t trong nui cy). Sau khi chn dng (cloning) cc th lai,
mi dng qun th t bo bt ngun t ch mt th lai (clone, hybridoma) s sn xut ra ch mt loi phn t khng th hon ton ging

nhau. l khng th n dng (MAb).

3.6. Khng th ti t hp (recombinant antibody - rAb)

* Khng th ti t hp l khng th th h th 3 c sn xut
in vitro. c im ca khng th ny l:
- c to ra bng k thut di truyn, khng l thuc vo ng
vt th nghim.
- C c tnh n dng v c ngun t mt t hp gen c la
chn, to ra mt loi khng th c hiu vi mt epitop nht
nh, sau c biu hin trn mt dng t bo vi sinh vt
hoc mt c th nht nh (c th l thc vt hoc ng vt)

45

Vic sn xut khng th ti t hp bng k thut di truyn cho

php nhn dng, dung hp v ti t hp gen to ra nhiu dng

khng th c hiu kp (bispecific) hoc ch l cc mnh khng

th c chc nng nh F(ab), mnh bin i mt chui (scFv)
dng cho vic lp ghp vi c t" min dch (immunotoxin)
to khng th iu tr bnh.
* 3 nguyn tc sn xut khng th ti t hp l:
C s lng gen sn c m ha cho khng th.
Chn lc c hiu qu cc gen thch hp trong vn gen.
Chn lc khng th c tnh i lc v c hiu cao.
* Tom tt cc bc sn xut rAb;
La chn cc gen t ngun gen.
Xy dng cc on gen ti t hp ca rAb v nhn dng.
Thit k cc vector chuyn gen v biu hin gen.
La chn vi sinh vt (thng l E.coli) biu hin gen, c th
s dng phage.
Tinh ch rAb t sinh vt biu hin.

3.7. Cc th th ca lym pho B (BCR )

Cc th th ca lympho B c to thnh t cc Ig c cu
trc ging nh mt phn t khng th ho tan nhng u
tn cng c ca cc chui nng c xuyn su vo mng t
bo lympho B. Vng xuyn qua mng t bo ca phn t Ig
c chiu di khong 20 gc axit amin v mt on ngn ca
trnh t tn cng c nm trong phn t bo cht. Cc BCR
ca lympho B chn bao gm mt IgM v mt IgD (mlgM,
mlgD) ca mng t bo, c mt chui nh ging nhau v cng
mt khu vc V. Cc chui |a v l s ghp ni ca cng mt
bn sao |i-5. Cc Ig mng l nhng monome (i2L2 ) BCR ca
lympho B ghi nh khng cha ng mlgD ngha l ch gm
mt lp Ig (c th l mlgM, mIgG3 hoc m lgG l V..V..) ngoi
ra cc m g c a lym p ho B cn kt hp vi mt h ete ro d im e

c hnh thnh t cc phn t Iga (CD79a) v IgP (CD79b).

Cc phn t Iga v IgP lin kt vi nhau bng mt cu disunfua nm ngoi t bo. Chc nng ca cc phn t Iga v
Igp l truyn dn tn hiu nh s kt hp ca BCR vi khng
nguyn dc hiu. S nhn bit khng nguyn ny c thc

46

hin vng d bin i ca phn t mlg. Vng ngp su

trong t bo cht ca cc Iga v IgP biu hin nh mt c
cht c th tng tc vi mt loi enzim gn bn trong mn
t bo pha t bo cht, l tirozinkinaz. Cng vi cc Iga
v IgP, tirozinkinaz tham ra vo truyn dn tn hiu trong
p ng min dch.

3.8. Cu trc ca cc th th lympho T (TCR)

Cc th th ca lympho T hoc TCR (T - Cell receptor) dng
heterodime do hai chui polipeptit xuyn qua mng t bo l (X
v p hoc v kt hp vi nhau. Mi chui polipeptit u bao
gm mt khu vc d bin i (V) tn cng N v mt khu vc
khng bin i (C) xuyn qua mng v bc l mt on rt ngn
pha trong t bo cht u tn cng c. C rt nhiu loi th
th dng y tu thuc vo cu trc ca chui y. Chng hn cc
chui Yi s lin kt vi chui 5 bng cu disunfua trong khi chui
2 c vng d bin i kh di v ch lin kt khng cng ho tr
vi 6.

Khong 70% lympho ca mu tun hon cha cc th th TClt

v ch yu dng ap (95% l a|3 v khong vi phn trm l a)
Trong khi , m t bo t l phn trm y cao hn v ch yu
l cc tuyn nhy. Cc t bo T biu b c dng rng ca ca
ngi khng c th th dng y nhng li c mt chut. Cc
th th ap c th lin kt vi cc khng nguyn c trnh din
vi cc phn t ca HLA ca lp I v lp II ngi. (HLA: Human Lymphocyte Antigen l khng nguyn ca cc t bo lympho ca ngi tng ng vi MHC ca cc loi ng vt).
Cc th th ap v y lin kt vi nhau trn mng t bo lympho T thnh mt phc h cng vi phn t CD3 . Phc h ny cn
thit bc l trn b mt ca cc th th TCR v m bo cho
s truyn dn cc tn hiu do s tng tc gia cc TCR vi
khng nguyn. Phc h ny bao gm 5 chui polipeptit: Cc
chui (yS v e)x2 bao gm mt khu vc kiu Ig ngoi bo v mt
vng xuyn qua mng, mt vng t bo cht.
Cc chui polipeptit ^ v 1 c phn ngoi bo rt ngn ch gm
9 gc axit amin, mt mnh peptit xuyn qua mng v hai vng
rt di nm trong t bo cht. Hai chui polipeptit c th dng

47

homodime (^Q hoc (iTr|) hoc dng heterodime (l^ri)- Cc vng

t bo cht ca cc chui polipeptit ny c mt k i u modun Ee
hoc ba kiu mun
ng vai tr truyn dn tn hiu khi
chng tng tc vi cc tirozinkinaz (Hnh 3.12).
Dng phc h TCR/CD3 trn c mt cc lympho Tap
thng lin kt vi cc phn t CD4 v CD8 ca cc lympho T b
u, tham gia tng tc min dch vi cc phn t phc h MHC
]3p II v lp I.
S tng hp cc chui polipeptit ca cc th th lympho T
cng c thc hin nh cc gen tdng ng v c th so snh vi
(c gen tng hp Ig.
Cng ging nh cc g. s tng hp mt chui polipeptit ca
'"'CR c chc nng lun lun cn s ti t hp ca cc mnh gen
( mt cc t bo T chn mi bn trong tuyn c. S sp xp
(c manh gn xy ra theo th t thi gian, trc tin l v ,
<au l ap, p v cui cng l a. C th l m ho cho cc
chui a v y c s sp xp cc mnh gen Va Ja Ca v Vy Jy Cy,
ln i vi cc chui p v 5 l cc mnh gen VpDp jp cp v V
3 J5 C. (hnh 3.13).

48

BCR H
r C'
,

sig

TCR

ui
CD3

y )
n

. J Ig-a
l
L
Ig-P
Ig-Pi iI .Ig-a

B
CD3

A> *' * *
;; cc
:
:~1 ^
5 ^

M
I

IIII
D

vp V a '^
\fu VU
Y f '

Hinh 3 .12 . Cu trc ca cc BCR v TCR

a. S cu trc BCR v hai hetero Iga - Igp.
b. S phc h TCR ap/ CD3. S ch r hai chui
chc nng a v p v hai n v chc nng ca phc h
CD3 l yeSe v
c. M hnh t chc ca phc h TCR/ CD3.
d. Ba kiu th th ySca lympho T.

49

V..

Scc
gen to 50
ra tnh
a dng 70
cc
mnh a

I
u

S)

S)

Scc
gen to
ra tnh
a dng
cc
mnh p

57

O p

2
12

It

Cc locus ca chui a v s ngi

V,,-Vn

lAJ^ u
h Jk
k

^1_-3

Dft <.? ./1 .

Cs

J i r i ; i 'I

Vs-

_ 41_Jn

u 'u |4 f v H

Locus ca chui p
^ ,1 -V |,n

0s1

J ) I_

C|,1

D,

i i i Mi i

J _______

i H l i m

Cp2

Locus ca chui
VJVj\

.... ........

f-

JJ

C.I

C -2

t " ~t

r4 H ^

Hnh 3.13. S lng cc mnh gen khc nhau c

dng to ra tnh a dng ca TCR ap (A)
S sp xp ca cc locus gen cho cc chui a, p, Y, 5 ca
TCR.

u.v
!
^

50

Tm tt chng III

1 . S nhn bit cc epitop ca khng nguyn c m bo bng

cc paratop nm trn phn t khng th hay cc immu noglobulin ho tan (Ig) hoc cc th th di dng slg mng u
bo lympho B (BCR) v cc th th ca lympho T (TCR).
2. Cc phn t nhn bit khng nguyn c hnh thnh t ciC
chui polipeptit, mi chui c t 2 n 5 khu vc (domain)),
c m ho bng cc gen sp xp v t hp li trong cc tt
bo B ( vi cc gen H, K, X ca Ig) v trong cc t bo tuyin
c (Thymocytes-t bo tuyn c s bit ho thnh lympho T')
i vi cc gen , s, p v a ca cc TCR.
3. Tnh a dng cc k phong ph ca cc th th cha ntg
paratop (trn 10 loi phn t khc nhau) c th c c nhi
cu trc heterodime ca hai dng chui polipeptit ( V h + V|1,,
Va + vp, V+ V 6), nh kh nng ti t hp trong cch sp xip
li cc gen V-J, V-D v D-J, nh tnh a dng ca cc mnh
gen ni J, cc vng N (Cc vng ni V-J v V-D-J ca TCR, V/D-J ca cc chui nng Ig) v cui cng nh t bin soma
cc dng t bo B, nhng khng xy ra t bin trong dng tc
bo T.
4. Nghin cu cc gen ca Ig v TCR c th a n nhng nig
dng thc tin trong lnh vc nghin cu min dch bnh l v/
mt s bnh ung th.

51

Chng IV. Cc phc h ph hp t chc ch yu

4.1. M u
Nh chng ta bit cc chng trc, cc th th (receptors) nhn bit khng nguyn ca cc lympho B (BCR) s tng
tc theo khng gian vi cc epitop ca phn t khng nguyn.
Trong khi cc th th ca lympho T (TCR) tng tc vi cc
peptit ca khng nguyn c lin kt t trc vi cc phn
t ca phc h ph hp t chc ch yu (MHC - Major histocompatibility complexes). Cc phn t protein ca phc h MHC
c m ho bi mt h thng gen ca phc h MHC nm trn
mng t bo trnh din khng nguyn APC (Antigen presenting
Vic pht hin ra cc sn phm protein ca MHC c tnh cht
ngu nhin v do tnh cc k a hnh ca cc phn t ny c mt
mi t bo ng vt. T ngi ta c th hiu r vai tr ca
chng trong qu trnh thi b cc mnh lai ghp. Khi nghin cu
c tnh cht h thng s kim tra di truyn ca qu trnh thi b
cc khi u chut, Peter Gorer (1936) xc nh r cc khng
nguyn c m ho bi mt locus ca MHC. Khng nguyn ny
c mt hng cu v cc t bo khc cho php kh nng thi b
hoc chp nhn cc mnh lai ghp ngha l kim tra kh nng
ph hp t chc ca m lai ghp. Cc cng trnh nghin cu tip
tlieo ca nhiu nh bc hc nh Georges Snell, Barij Benacerra,
Hugh Mac Devitt cho php hiu bit cc gen cc locus khc
nhau ca lp I v lp II ca MHC. Cc cng trnh ca Jean
Dauset t 1958 cp ti vic nghin cu MHC ca loi ngi
v c gi l h thng HLA (Human Leucocyte Antigens) cho
thy chc nng sinh hc ch yu ca cc phn t HLA l trnh
din peptit khng nguyn cho cc lympho T.

52

4.2. Cu trc chung ca h thng HLA

HLA ca ngi hoc MHC ca ng vt c c tnh bo th cac
tt c cc loi. l mt h thng nhiu gen, nhiu alen v
biu hin ng tri. H thng HLA l mt tng th cc gen nh
khu trn mt mnh cnh tay ngn ca nhim sc th s' 6 , chim
khong mt phn nghn ca genom ca ngi (bng p21.3). Cc
locus ny c nhm li thnh hai lp: lp I bao gm gia cc
gen HLA-A, B v c v lp II c t nht t 23 n 25 gen ca vng
HLA-D (hnh 4.1).
Ngoi cc gen m ho cho cc phn t ca HLA lp I v lp II.
ngi ta cn tm thy cc gen khc ca MHC kim tra mt s
giai on trnh din khng nguyn. l cc gen TAPl v TAP2
m ho cho mt cht vn chuyn peptit, cc gen LMP2, LMP7
m ho cho cc yu t ca th proteasom cha cc proteaz, cc
gen ca protein sc nhit (HSP70-2 v HSP70-1 v.v...). Cc protein ny c chc nng lin kt vi cc protein b s"c nhit loi
tr chng ra khi c th. Ngi ta cng tm thy phc h MH('
cn c cc gen C2 , BF, C4A, C4B m ho cho cc thnh phn ca
b th, cc gen TNFa v TNFp m ho cho cc yu t' hoi t un^:
th. Tt c cc gen ny u c tnh cht a hnh, u biu hin
ng tri v lin h cht ch vi nhau.
- Tnh a hnh ca cc gen trn th hin tnh a alen. T
dn n kh nng t hp cao trn mi nhim sc th v con s
t hp cc kiu gen c th vt qu 10 '. S khc nhau v alen
c th tng ng vi kh nng t bin ca mt hoc nhiu
baz, hoc thng xuyn c s thay th khong cch gia cc
trnh t m ca gen, lin quan n c ch bin i gen.
- Tnh biu hin ng tri th hin mi mt alen trn mt haplotip. Mt ngi thng thng l d hp t cho mi mt locus
v mt nhm HLA ca ngi c xy dng t nhiu ch
ci trong mi ch ci c trng cho mt locus v c
truyn li t cha v m.
- Mi lin quan hp th hin ch tt c cc gen u c
truyn li thnh mt mng t cha m ca nhng a tr. Nu
ngi ta gi a v b l cc haplotip ca cha, c v d l cc haplotip ca m th mi a tr u c di truyn t mt haplotip ca cha v mt haplotip ca m v s c 4 kiu tr em l
ad, ab, bc v bd: Do xc sut cho cc HLA khc nhau
nhng a tr l 25%.

53

4.3. Cu trc cc phn t v h gen ca HLA

Cc phn t lp I ca HLA c hnh thnh t s kt hp ca
mt chui nh P2 microglobulin (B2 m) v mt chui nng a.
Chui nh P2m c m ho bng mt gen nh khu nhim sc
th s" 15. Phn t chui nh P2m c cu trc hnh cu c v
chc bao gm 99 gc axit amin c t chc thnh 2 l gp p lin
kt vi nhau bng mt cu disunfua (gia sistein 25 v 81).
Chui nng a c hnh thnh t 3 khu vc ngoi bo l a l, a 2
v a3, mi khu vc c m ho bng mt exon. Ngoi ra chui a
cn c mt vng xuyn qua mng t bo v mt vng nm trong
t bo cht (Hnh 4.1). Cu trc 3 chiu ca chui a to ra mt
rnh gia cc khu vc a l v a 2 , c y rnh l mt l gp p v
cc b rnh to nn xon a.
Chnh dng cu trc vng rnh ny to kh nng tng tc
c hiu vi cc peptit ca cc phn t khng nguyn ca bn
thn hoc cc khng nguyn l khng phi ca bn thn.
Phc h gen ca HLA lp I c biu hin ch yu l HLA-A,
HLA-B v HLA-C. Ngoi cc gen HLA-A, B v c to ra sn phm
irn, ngi ta cn nhn bit c mt s' gen khc nh HLA-E,
F, G c chc nng kim tra s tng hp cc protein ca lp I.
Cc gen HLA lp II (vng HLA-D) bao gm t 23 n 25 gen
c nhm li thnh ba phn vng ch yu l DR, DP v DQ.
Mt s gen c tnh a hnh, mt s" gen l n hnh. Cc phn t
HLA lp II c hnh thnh t hai chui polipeptit a v p, mi,
mi chui u gm hai khu vc ngoi bo. Cu trc ba chiu ca
chng c th c dng gn ging vi cu trc ca cc phn t lp
r. Cc vng tn cng N ca phn t c nh khu kh xa bn
ngoi mng t bo v c tnh t chc a hnh, bn trong t bo,
cc phn t HLA lp II lin kt vi mt chui polipeptit khng
bin i c m ho bi mt gen nh khu nhim sc th s 5.
Mt hoc c hai phn t DR c biu hin theo th n bi
(haplotype). Trong tt c cc trng hp, chui a c m ho bi
mt gen DRA khng mang tnh a hnh. Chui p c m ho bi
mt gen DRBl cho mt phn t u tin v c m ho bi mt
trong cc gen DRB3, )RB4, DRB5 i vi phn t th hai.
Trong mt th n bi no , khng th cng mt lc tn ti
c ba loi gen DRl, DR8 , DRIO v cng khng th c thm mt
phn t th hai. Cc chui a v p ca phn t DQ c m ho

54_________________________________________________________________

bng cc gen DQAl v DQA2 tng ng. Cc gen DPAl v DPBl

m ho cho cc chui a v p ca DP. Sn phm ca cc gen DMA
v DMB l chui ap heterodime, khng ging vi cc heterodime
ca cc gen DP, DQ v DR ng thi rt him khi biu hin trn
b mt t bo. Cc gen DOB v DNA t c phin m cc lympho v c th m ho cho mt phn t HLA-DO. (Hnh 4.2)

HLA-I

HLA-II

Mng
Vng t bo cht

Hnh 4.1: S cu trc phn t HLA-I v HLA-II:

HLA lp I, chui nng a xuyn qua mng lin kt khng
cng ho tr vi chui nh P-microglobulin; HLA lp II,
c hai chui u xuyn qua mng v lin kt khng cng ho
tr vi nhau. (Theo M. Peakman v D. Vrgani, 1997).

55

Tm ng (centromer)

ii)

Lp I I

Lp I I I

Lpl .

>)
f4 '>

/-.-

DP

()

, I 4,

: i

< 4 A

<

nQ

fi

":/

(M IUM A in ('2

I)K
>vf

t '

t i'> f

I r^f

V lAK '

r p - -- v - f- -'v -Hj-p i'j -V '

4t . ' A . '

fi)

Or>

/1

t-\f

tL iA

HvSPTNT
_
# .'

)M

A
o n

t*:i H t

DQ

4 ^ :.f :.-.
O'

DR

Hnh 4.2, S v tr v cu trc gen ca HLA nhim sc th

s' 6 (theo M. Peakman v D. Vergani, 1997)
a) V tr cc cm gen trn nhim sc th 6.
b) S sp xp cm gen lp I, lp II, lp III.
c) Chi tit bn gen vng lp II: DP, DM, DQ, DR. cm gen
lp I I c cha cc geii LMP2 v LM P7 m ha cho 2 peptit tham
gia vo ch bin khng nguyn ni sinh, T A P l, TAP2 l cc gen
in ha cho protein vn chuyn peptit khng nguyn.

4 .4 . S phn b, iu ho biu hin v chc nng ca

cc phan t HLA
Cc phn t HLA lp I: c mt phn ln cc t bo ca c th
(t 1 0 ' n 5.10 phn t/mt t bo) c bit nhiu cc t bo
lmpho v i thc bo). C t hn t bo gan cha rt t hoc
bng khng hng cu, t bo thn kinh trung ng, mt s loi
t bo biu m ca ty v tuyn nc bt, v.v... Mt s" t bo ung
th khng c cc phn t lp I. T l tng hp v biu hin trn
mng ca cc phn t HLA lp I tng ln nh tc ng ca inteferon a v 3.
Chc nng ca c c phn t HLA lp I l trnh din cc peptit
khng nguyn cho cc lympho T cha ng phn t CD8 bc l
trn b mt t bo. Cc lympho T ny gi l Lympho T- CD8 *

56________________________________________________________ _

cha ng mt glycoprotein dime, lin kt c hiu vi cc phn

t HLA lp I trong tng tc min dch. Cc peptit khng
nguyn c trnh din bt ngun t khng nguyn l do qu
trnh phn hu protein ni sinh (endogenic proteolysis) din ra
trong t bo trnh din khng nguyn (APC). Chng hn cc
thnh phn t bo vi khun, cc protln virus. Qu trnh phn
hu khng nguyn l din ra proteasom l phc h cha ng
cc proteinaz ca APC. Cc peptit c trnh din c kch thc
khong ^^c^jaxit|amin c vn^un vo kK>ang li ni cht
kt
vc cc phn t lp I v vn chuyn ra mng t bo ca
APC.
Cc phn t HLA lp II bnh thng bc l hn-ch ci mt s t
bo ca c th. Mt ca chng c bit cao cc t bo chuyn
ho ( 10 phn t/ mt t bo) trong qu trnh trnh din khng
nguyn cho cc t bo lympho T-CD4*. Cc t bo trnh din
khng ngyn c th l cc lympho B, cc t bo c thu (t bo
biu b Langerhans, t bo khe hch lympho), cc t bo mono,
i thc bo, t bo biu m ng h hp, t bo ni m thnh
mch v c lympho T. S bc l cc phn t HLA-lp II s tng
ln di nh hng ca inteferon y, ca IL4, IL13, TNFa v p v
gim xng di tc dng ca prostaglandin PGE-2 . Biu hin
bt tng ca cc phn t HLA lp II mng t bo thng lin
quan n s thiu ht min dch nghim trng.
Chc nng qUan trng ca cc phn t HLA lp II l tng tc
c hiu vi lympho T-CD4* sau khi cc phn t HLA lp II
lin kt vi peptit khng nguyn. NH vy tng tc kiu tm
pMn t-(trirttlecular interaction) gia f CR, pptit lin kt vi
phn t lp I hoc lp II m bo cho kh nng tng tc min
dch c hiu v c hiu qu.
Chc nng chung ca cc phn t MHC l du hiu b mt
ch cc lympho T gy c t bo v cc lympho T b tr nhn
bit Gc du hiu b mt MHC cng tham gia vo qu trnh bit
ho cc t bo lympho T. Mt vai tr quan trng ca mt s" phn
t.MHG lin quan n h thng ni tit ca c th. Chng hn
dQg t bo ung th Daudi khng bc l khng nguyn lp I v
kbpng c 8 tng hp P2 microglobulin 32m) s khng c cc th
th tip nhn insulin vo th th t bo.
on 8 l thuyt v cc nonapeptit khc nhau l 5 ,1 x 1 0 ". S
in kt ca cc nonapeptit ny vo phn t HLA s dng t i
n 5 gc axit amin cc v tr tn cng hai u ca peptit. Phn

57

gia ca peptit tng tc vi paratop ca TCR. Phn ny c th

ni ln so vi rnh lin kt peptit c bit trng hp ca cc
phn t HLA lp II v cc phn t HLA lp II c th lin kt vi
cc peptit khng nguyn c chiu di ln hn. Cc chui bn ca
peptit c c nh vo cc ti v ni vo cc xon a v y gp
p ca rnh. Cch cu trc nh vy ch cho php mt peptit hoc
mt lng rt nh cc peptit l khng phi ca bn thn c kh
nng c nhn bit bi cc t bo T ca mt c th (hoc cc
phn t MHC ni chung) qui nh. (Hnh 4.3 v hnh 4.4)

Hnh 4.3: S cu trc rnh lin kt MHC-I. Cc peptit c

lin kt vi rnh MHC-I bng cc phn u tn cng ca chng

Hnh 4.4; S cu trc rnh lin kt MHC-II. Cc peptit lin kt vi rnh MHC-II bng s tng tc dc theo
chiu di ciia rnh lin kt

58

4.5. H thng HLA in quan n qun th chng tc

v cc bnh l
S kt hp gia mt alen ca mt locus v mt alen ca locus
khc i khi xy ra mnh hn so vi s kt hp ngu nhin. S
mt cn bng ca mt mi lin kt cc alen thng c trng cho
mt qun th chng tc. Chng hn s kt hp gia cc gen HLA
ca lp III xy ra tng ng vi cc dng chng tc BFS, C2C,
C4A3 v C4B1 c mt ti 40% chng tc chu u (Caucasoid)
v ch c 12 % chng tc da en. T cc nghin cu v' s
phn b gen ca HLA s cho php tm hiu lch s c dn ca
mi vng v s di c ca cc qun th ngi.
Ngi ta cng nhn thy c gn 40 loi bnh l c lin quan
vi h thng HLA. Mt s bnh gy ra do ch mt gen HLA nh
bnh huyt sc t t pht, thiu ht enzim hydroxylaz-2 1 , thiu
ht b th C2 hoc C4. 0 cc ngi ng hp t mang gen bnh
l th triu chng bnh thy r c t l mc bnh l 1/ 100.000
ngi. Mt s' bnh khc c lin quan n mt gen c kh nng l
DR2 gy ng m mt. Mt s alen ca lp II cng gy ra bnh t
min. Bnh vim khp t sng lin quan n mt khng nguyn
HLA-B27 c xc nh bng phng php huyt thanh thuc
mt phn t ca HLA lp I gy ra.

4.6. Cc phng php nghin cu h thng HLA

- Phng php huyt thanh hc phn loi HLA da vo cc
phn ng ca cc lympho mang cc khng nguyn HLA trn
mng t bo c th phn ng vi cc khng th v b th ca
chng. Ngun khng th c th l d khng huyt thanh (alloantiserum) nhn c bng cch gy min dch cho ngi
(truyn mu hoc ghp m l ...) hoc to khng th n dng.
- Phng php ho sinh bao gm vic phn tch in di phn
vng ng in (isoelectrofocalisation), in di hai chiu, xc
nh s khc nhau v khi lng phn t v s tch in ca
cc phn t HLA c tch ra bng cch kt ta vi khng th
khng HLA.
- Phng php sinh hc phn t c th nh loi tnh a hnh v
chiu di ca cc mnh gen gii hn (RFLP - Restriction frag-

59

ment Length polymorphism). Cc mnh gen c tch ra c

kch thc khc nhau bng in di, sau c chuyn thm
trn tm nitroxenluloz v c nhn bit bng cch lai vi mt
mu d c hiu vi mt gen HLA (k thut Southern). Cc
phng php hin i xc nh locus ca lp II da vo vic s
dng cc mu d oligonucleotit c hiu vi mt alen hoc
nhm cc alen (HLA oligotyping) v c hiu vi mt trnh t
chung ca tt c cc alen. Cc mnh gen s c nhn ln
bng PCR nh mt on mi v tnh a hnh c pht hin
bng cch lai phn t hoc phn tch trnh t ADN. Cc
phng php ny rt chnh xc, c th thc hin trong 4 gi'
vi my c so mu.
- Phng php t ho da vo s tdng tc c hiu gia cc
phn t HLA v cc th th ca lympho T.
Phng php i hi s dng phn ng trn lympho c s
dng cht tin thn phng x
tim idin o s sinh sn ca
cc lympho thch hp.

60

Tm tt chng IV

1 . Phc h MHC, ngi gi l HLA l mt tng th bao gm cc

gen nm phn cnh tay ngn ca nhim sc th s' 6 , c tnh

cht a hnh, lin kt cht ch vi nhau (c truyn li ton

b t mt c th n bi halotip ca cha m n con ci) v u
biu hin ng tri.
2 . Cc phn t HLA lp I (HLA-A, B, C) biu hin a s cc t
bo ca c th, trong khi cc phn t lp II (HLA-DR, DP,
DQ) phn b" hn ch hn, c cc t bo trnh din khng
nguyn cho cc lympho TCD4^.
3. S biu hin cc khng nguyn HLA c iu ho c hiu
bng cc xitokin khc nhau v bin i theo cc iu kin sinh
l v bnh l.
4. Cc phn t HLA ca lp I v lp II c nh cc peptit khng
nguyn ca bn thn hoc khng phi ca bn thn bng cc
v tr a hnh ca chng. Phc h peptit - HLA tng tc vi
TCR, trong HLA lp I lin kt vi lympho TCD8 * v HLA
lp II lin kt vi lympho T-CD4*.
5. H thng HLA cho php thit lp mt giy thng hnh hay
chng minh th sinh hc cho mt c th; nh c th tm
hiu lch s mt qun th ehng tc v nguyn nhn ca mt
s bnh l c lin quan, c bit l cc bnh t min do mt s
allen bnh l kt hp vi nhau c th ng hp t.

61

Chng V. B th

5.1. Khi nim

B th (complement - vit tt l C) l dng hp cht bao gm trn
bn mi loi protein (khong 5% protein ho tan ca hyt tng)
v cc protein mng (cc th th v cc yu t" protein iu ho) c
kh nng tng tc ln nhau v phn ng vi mng t bo sinh
hc. Chc nng ca b th l :
- Tham gia vo qu trnh thc bo cc vi sinh vt.
- Trung ho cc virus v loi b cc phc h khng nguyn khng
th.
- iu ho p ng min dch.
Hot ng ca b th phn ln ph thuc vo s tng tc ln
nhau gia cc protein b th v cc th th t bo c hiu, ng
thi c khuynh hng hot ho nhanh chng v din ra ti ch.
iu c thc hin bng c ch khuch i v kim sot c hiu
qu. Hot ng ca b th c thc hin bng ba con ng:
1 . Con ng c in (classical pathway) c hot ho bng phc
h khng th - khng nguyn ngha l ch xy ra khi khng th
kt hp vi khng nguyn.
2 . Con ng bn cnh (alternative pathvvay) c hot ho trc
tip bng mt s" polixacarit ca vi khun m khng cn c mt
khng th. C hai con ng hot ng ca b th u cn phc
h tn cng vo mng hoc phc h phn hu mng t bo vi
khun (C5b-9) v cc ion
v
Do gn y ngi ta
cho rng c 2 con ng trn u khi ng cho mt con ng
thc 3 l con ng tn cng mng (Hnh 5.1).
3. Ngi ta cng tm thy con ng hot ho b th nh lectin MB
(gn ging c ch hot ho c in). Lectin MB c vai tr hot ha

62

b th thi k c th th u, th hin chc nng p ng min

dich bm sinh.

5.2. Cc protein ca b th
Thnh phn ca cc protein tham gia vo con ng c in v
phc h phn hu mng (phc h tn cng mng) l nhng b
th c k hiu t Cl n C9. Hp cht C l c to thnh t 3
tiu n v l Clq, C lr v Cls (xem hnh 5.1). Cc mnh pepti t
do enzim phn hu c k hiu l C3a, C3b. Ch i k hiu cho
mt phn t b mt hot tnh, v d C3bi. Cc loi protein ca
con ng bn cnh xen k c k hiu bng cc ch ci im.
Chng hn p l propecdin, yu t B l C3 tin hot ho, yu t D
l C3 tin hot ho convectaz. Trng thi hot dng ca cc phC
h b th c k hiu c gch ngang trn. V d: C^bCaa.
Cc protein ca b th c khuynh hng t pht hnh thntti
cc phc h thun nghch bao gm nhiu phn t. l trng
hp vi Clq, C lr v Cls khi c mt ion Ca'* v i vi C4t,
C2. Trng hp i vi C3 v yu t B, cn phi c ion Mg* vi
i vi hp cht C5, C6 , C7, C8 v C9 l 5 hp cht c th kt
hp vi n h au h n h thnh phc h tn cng m ng (M em brane

Attack Complex- MAC).

c tnh hot ng rt c bit ca b th l lin kt vi b(
mt ca cc vt th c hot tnh sinh hc nh phc h khnfg
nguyn-khng th, cc t bo, cc vi khun, virus, k sinh trnjg
v.v... Khi cc yu t C3 v C4 b phn hu s to ra mt v tr lim
kt vi mng trong thi gian rt ngn (di 10 phn nghn giy)..
Nh lin kt ny lin quan n mt cu tio-este bn trorig
tng i khng n nh v c kh nng c' nh mt vt tht
bng mt lin kt cng ho tr. Nu thiu mt cht tip nhn b
th ng lc, phn t b th t do trong tun hon mu nhanlh
chng b mt hot tnh. V trn b mt mng t bo ca chnlh
bn thn c th c axit sialic nh l mt tc nhn bo v chn{g
li s lin kt ca C3 b nn rt ngho v tr tip nhn b th. Trii
li, mng t bo vi sinh vt hoc t bo ng vt khc bit V(

chng loi pht sinh kh giu v tr tip nhn b th, s lo iiu

kin tt cho s lin kt vi b th.
Cc protein b th c tng hp gan, cc t bo biu m(
rut (Cl), cc t bo mono v i thc bo. Thi gian bn hu'

63

ca C3, C4 v B l 24 gi nn chng cn c tn g hp li hay

i m i.

('c thnh phn C2 , C4 v B c m ho bi cc gen ca b

th c tnh a hnh alen.

Hnh 5.1 Phc h b th C l q - C l r - C l s .

a. S phc h C lq (C lr Cls)v, trong C lq gm 6 tiu n v c
cu trn tng t 6 bng hoa tuy lp v 6 ci ui collagen lin kt vi
2 phn t C lr v 2 phn t C ls. Cc u trn C lq lin kt vi vng Fc
ca cc Ig.
b. nh hin vi in t phng i 500.000 ln ca phc h C lq (C lr
(] ls >2 (theo K.B.M.Reid).

5.3. Cc tin trnh hot ho b th

Nh trnh by hnh .2 s hot ho b th din ra theo
ha con ng v theo dy chuyn. Thnh phn u tin ca b
th c hot tnh phn gii protein s phn hu c hiu thnh
)hn th hai thnh hai mnh peptit v mt trong chng li c
hot tnh phn gii protein c hiu i vi thnh phn th ba.

5.3.1. Con ng hot ho c in

Con ng ny c thc hin bng s tng tc ca C l vi
mt phn t IgM lin kt vi khng nguyn hoc khng
nguyn lin kt vi hai phn t IgG (IgGj v IgGa) (hoc IgG.,
nhng km hiu qu hdn). Trong phc h C l ch ring tiu n

64

v (H q kt hp vi khng ih. R t him k h i s hot ho dic"

khi dng trc tip nh cc cht nh protein phn ng c, cc

lip o p o lixacarit, hoc mt s viru s.

Phn t Clq c cu trc trng ta b hoa 6 bng tulip, (hnh

5.1) c phn Kii htih si dng colagen v 6 tiu n v h n h cu

lin kt vi cc vng Fc ca IgG v IgM. Khi c ml ion Ca,

Clq hot ho C lr v ( ls. Cls d c hot ho s phn hvi
ng thi C4 v (' C2 ko theo vic h n h thnh cc m nh C4b v
C2 a. CMb v C2 a hnh thnh mt phc h gi l C3 convcctaz c
in tc l mt enzini lng )hn t n dnh khi c m l ion Mg-*

t,i|) tc phn hu ('3 tlinh hai mnh C3a v C3b. i^hn t c.5b
li kt hp VI phc h C4b2a thnh phc h mi l. CMb2a3b I

kh Iing phn hu C vi (iu kin l C c c diih vo phn

t C 3 h .
S h o t h(j theo con lii' c din dc diLi ho bng C lIN H (cht c cli C l) . ('hVt c ch C l- IN H km hm s hot ho
( ' I r v C ls kh i n kt h.p V(3i cc enzim C l r v C ls v lm p hn
li cc on/,im cu C lq . Nu thiu ht bm sin h C l- IN H s dn ti
cc bnh p li mch. Mt lot proloin lin kt vi C4 cng c tc
dng diu ho l C lbp ((M b iiid in g i)rotein). Cul cng hot dng
ca phc Ii C'll)2a cng dc kim so t biig cc )roteiii c m t
b m t ca nhiu loi l bo; C D 5 5 (D A F ), C D 3 5 ( C R l) v
(M C P ) (h;iy cn gi l p ro lein cofactor ca m ng t bo
CD 46) (xem h iili 5.2A).
N hng protein b mt t bo Ir n d lm gii hn s hot

ho b tli cc t ho ging nhau.

Cc I)r lein C lr , ( 'Is . C2, 1.5, H. C-lbp, M C P, 1)AF. C K l. cng
nh CR2 C6 v (7 (lu dc liiih lltiih l cc ddn v c trnh t

lj) li t 60 dn 70 axil amin, Irong d con s'khc nhau Lhng

l 2 axit am in ((i vi C l r v C ls ) v khc nhau ti 56 a x it am in
l C4bp.

5.3.2. Con ng hot ho b th nh lectin MB

Lectin M B l loctin lin kt vi M an n an (Mann^n B in d in g
loctin) c cu li c lYl ging C lq bao g m phc h c 6 u vi
cc trc si cli Lliuc dng Colltctin (lectin dng Collagen). kl
hp vi 2 loi Zymogcn )iotoase sc rin l M A S P l v M A SP 2. K h i
M A S P l v M A S P 2 kt hp vi si tr c loctin M B s Lo I'a plic

65

h Kng ih C lr v ( ls lin kl vi Clq trong con ng hot

ho c dien,
Khi ) h c h MB 1(C I I I 1 - MASPl MASP2 lin kt vi b mt
ti'u' nhn gy bnli s ])hn lui C2 v C-l v to ra C3 convertaso
ging nh vai tr ca ( lqrs trong con dng hot ho c in.
N<U(i thiu ht lectin M B th hin kh nng d b nhim trn g

rat cao giai ocn S(3m ca tui th u. iu d chng t vai tr

quan trng ca leotin MB ca COII dng hot ho b th trong c
ch bo v vt ch cn non tre Lroti giai don p ng min dch
bm sinh.

66

C4

Carboxypeplidaz N

C3 C arboxypeptidaz N

C4a

C3a

C 3 b ,-__ Yu t
C4b2a.

C l-IN H

C2b
C4b2a3b
C5 convertaz

(B)

(A) v theo con ng bn cnh (B).

K hiu (-) l iu ho km hii, (+) l iu ho kch thch
ClINH: cht c ch C l
DAF: yu t' thc y s ph hu C4b (decay-acceberating Pactor)

67

Con ng bn cnh

Con dng c in
C4l)2a3b

C3bBb3b

(C)

C5

C5b
C6. C7
Protein s
v
SP-40,40
C5b67

Hnh 5.3 Hot ho b th giai on tn cng mng

K hiu
(-) l iu ho km hm
(+) l iu ho hot ho

68

5.3.3. Con ng hoat ho bn canh v cc yu t hoat ho

b th
Con ng ny s dng C3, cc yu t B v D v cng s dng cc
polixacarit nh inulin, zimozan (ca nm men), cc endotx)xin VI

khun v mng hng cu th. S hot ho theo con ng bn cnh s

d dng khi c thm khng th. Mi ln c hot ho, con ng hot
ha nv s c tng nhanh bng mt vng khuch i t ti s hnh
thnh C3 convectaz. C3 convectaz c n nh nh propecdin (mt
loi protein gy ra s c nh C3 convectaz v lm n nh n). Khi c
mt ion
C3b v yu t" B hnh thnh mt phc h lng phn t
CbB (hnh 5.2B).
Yu t D nh mt proteaza serin lm phn hu yu t B trong phc
h C3bB hnh thnh phc h convectaz C3 bB. Convectaz C3 bB s
phn hu C 3 hnh thnh cc phn t mi l C3b s lin kt VI
mng t bo vi khun. Sau C3 l C5. C5 s to phc h vi C3b v tr
thnh c cht ca C3bBb. Nh mt peptit nh c gii phng ra l
C5a, ti'0ng khi mnh peptit C5b s lin kt vi mng t bo. C5b li
lin kt vi C6 , C7 v tip theo l C8 v mt phc h c hnh thnh
s gy ra s thay i phn t C9, mt thnh phn b th cui cng ca
dy phn ng a n s trng hp C9 (bao gm t 10 - 16 phn t.
to ra polyme hnh ng). Cc phc h vi b th c phn li v ci vo
lp kp lipit ca mng t bo vi khun v trng hp li thnh phc h
tn cng mng c dng hnh hg. Phc h tn cng mng C5b-9 n k
hiu MAC (membrane attack complex) s to ra mt ng hm
xuyn qua mng c ng knh 10 nm to iu kin thrn d dng cc
cht in li v nc nh Na* hoc H^o. Dng
v H2O to ra p
sut thm thu lm ph v mng t bo vi khun.
Cc yu t H v I tham gia vo s iu ho vng khuch i. Yu t/>
H lin kt vi C3b cnh tranh vi yu t B ko theo s phn li nhanh
chng phc h C3 convectaz C3 bBb v lm mt hot tnh ca n. Hdn
na H lin kt vi C3 b cn c vai tr l cofactor enzim ca yu t' I, cho
php yu t I phn gii C3b thnh C3bi bt hot. Chnh yu t I cn c
tc dng phn hu C3bi thnh C3c ho tan C3d C3 d c nh vo
mng t bo vi khun. Nh trn ni cc protein mng nh DAF v
CRl cng c vai tr kim sot hot ng ca phc h C3 convect
C3bBb.
Yu t'c ngun gc thn: yu t thn (nephritic) (C3NeF) l mt t
khng th (autoantibody) IgG c hng chng li C3 cnvectaz. T

69

khng th ny lm bn phc h C3 convectaz v to cho n bn vi tc

dng ca yu t H.

5.4. Hiu qu sinh hc ca s hot ho b th

Nhng hiu qu sinh hc ch yu ca s hot ho b th l:
1 Gy cm ng phn ng vim bng vic gii phng ra cc anaphylatoxin - c t gy phn v.
2 To ra hin tng opsonin ho cc vi sinh vt hoc cc t bo
l nh tc dng ca C3 b, C3bi v C4b cho php c nh cc vt
th l vo cc th th CRl v CR3 ca cc thc bo (t bo a
nhn trung tnh, cc t bo mono v i thc bo). Hin tng
opsonin ho ng vai tr bt buc i vi kh nng thc bo.
3 To ra s phn hu mng t bo vi khun hoc cc t bo
mu (gi ci) v cc virus c v lipit.
4 To iu kin trnh din khng nguyn cho cc lympho B
c thc hin bi cc t bo nang hnh tua c cc th th CRl
CR2 v CR3 mc cc trung tm mm pht sinh v sn
xut cc tn hiu sinh sn (CR2) v cc tn hiu bit ho (CRl)
i vi cc lympho B. S lin kt ca khng nguyn vi C3 b
cn cho php s thm nhp v s trnh din khng nguyn cc
t bo lympho T.

55. B th v cc c ch trn thot ca vi sinh vt

Rt nhiu vi sinh vt to ra s hot ho b th bng cc con
ng c in hoc con ng bn cnh nhau nh cc proteaz ca
cng hoc nh s hot ho plasmin ca mu.
Tuy nhin, tri vi vai tr ch yu ca b th l thc hin c
cl bo v chng li nhim trhg, nhiu loi vi sinh vt to ra
h thng khng vi tc ng ca b th nhm trn thot h
tlng min dch. Cc c ch trn thot vi sinh vt c th nh
SU;

- Hnh thnh lp v bc (capsul) ngn cn kh nng hot ho b

th theo con ng bn cnh (chng hn Streptococcus pneumoniae, Haemophilus influenzae ...)

70

- Lm c nh phc h tn cng mng MAC cch xa thnh t

bo vi khun, hoc to i khng kh nng ci vo mng ca

phc h MAC.
- Tit ra protein ho tan c nh C3b cch xa vi khun.
- Phn hu cc th n h phn protein lin kt vi b mt ngoi
mng t bo, lm cn tr s tip xc vi cc th th CRl, CR2,
DAF thm nhp vo t bo t bo vt ch hoc trn thot
khi tc ng ca b th (chng hn Trypanosoma cruzi, Candida albicans hoc cc virus herpes).

71

Phc h Ag - Ab

mannfiza ca b mt
vi khun

b mt vi khun
(LPS, Zimozan..)

C1
C4
C2

LM B-M ASP
C4
C2

C3
B
D

C3 - CONVBRTASE

C 4a\ C3 a, C5a

C3b

Cc thnh phn b
th khc; C5b, C6 ,
C7, C8 , C9

Cht truyn dn Lin kt vi th th b Phc h MAC phn

peptit gy vim,
th trn b mt I hc hu cc tc nhn vi
huy ng thc bo
bo
khun
* v t bo
ch
Opsonin vi khun v
loi b phc h min
dich
Hnh 5.4. S tm tt m'i quan h v h qu
ca ba con ng hot ho b th

72

5.6. Cc h thng khc ca huyt tng tham gia vo

cc c ch bo v v c ch vim
B th l mt trong bh h thng cc protein ca huyt tng
kim sot hin tng bo v v c ch vim. Ba h thhg khc l
h th n g tip xc, h thn g ng m u v h th n g ti u si h u y t
(b rin olysis system ).

H thng tip xc bao gm cc yu t' Hageman HF (tc yu t'

XII), prekalikrein, yu t XI v cc kininogen c phn t lng
thp (LMwK) v cc kininogen c phn t lng cao (HMwK). H
thng ny c hot ho bng cc cht v c nh silic, amian, cc
tinh th pirophotphat canxi v.v hoc bng cc hp cht hu c
nh endotoxin vi khun, polixacarit sunfat, heparin, glycozamino glycan v.v... v cc cht c b mt in tch m. S kt
t (aggregation) ca cc thnh phn ny ni chung din ra mt
v tr bn ngoi mch mu ko theo vic hot ho cc chui phn
ng enzim phn gii protein, gii phng kalikrein, mt proteaza.
S phn gii protein bng cc proteaza trong h thng tip xc
ca qu trnh ng mu a n gii phng nhiu mnh peptit
hot ng nh yu t Xlla, Xla, aHFa, pHFa tham gia tip tc
tng tc vi yu t IX v b th (gii phng C5 a). S hot ho
h thng tip xc c th xy ra hoc c khuch i nh cc t
bo a nhn trung tnh v lm tng hp prostaglandin (mt dn
xut c hot tnh dc l ca axit arachidonic) v hot ho colagenaza lm tng tnh thm cc mao mch v gim huyt p ng
mch. H thVig ny c s dng trong qu trnh sc nhim
khun cc phn ng phn v v rt nhiu phn ng vim. iu
ho s hot ng ca h thng tip xc c thc hin nh ClINH (i vi HFa, Xla, kalikrein). Phc h antitrombin III,
heparin, al-antitripsin (i vi kalikrein, Xla) v a 2 anti plasmin.

5.7. Cc bnh l pht sinh do thiu ht b th bm sinh

Nhng s thiu ht ng hp t ca Clq, C4 (kiu ng hp
C4A, QO, BQO) v c bit l C2 (vi tn s 1/ 10 0 .000 ) thng
ko theo cc bnh lupus ban h thng. S thiu ht di truyn
mt phn C4 (C4A v/hoc C4B) thng gp cc bnh nhn

73

inc bnh t min (lupus ban . hi chng Gougerot Sjogren,

bnh tiu ng type I, (tiu ng ph thuc insulin), bnh
vim gan t min.
S thiu ht C3, B, D v propecdin ko theo s nhim khun
l. pht. S thiu ht C5, C6 , C7 hoc C8 lun km theo nhim
khun gram m Neisseria sp. Bnh ph n do lon thn kinh
chc nng mch (angioneurotic oedem) l do gim s lng Cl[KH (chim 85% trng hp) hoc do gim chc nng ca ClINH (chim 15%). T l mc bnh trng hp ny l 1/150.000.
C c bnh nhn c s suy sp t l C4 v C2 . C th tim truyn
tn thi Cl-INH tinh ch v mt hot tnh trong trng hp
b chn thdng hoc sau gii phu.
S thiu ht cc yu t H v I d gy ra nhim trng ti pht
v i k h i gy b n h m ay, bnh th iu m u do tan h u y t, bnh

vim thn tiu cu, trng hp ny t l C3 suy gim mnh.

Tliu ht DAF v cc cht c ch khc ca phc h tn cng
ming gy ra bnh hemoglobin niu v m, lm tng kh nng
thiu mu do b th ph hu hng cu.

74

Tm tt chng V

1 . B th l mt tng th cc protein c kh nng

c hot ho

lin tc nh con ng hot ho bn cnh (theo kh nng min

dch k h n g c h iu ) hoc nh con ng h ot ho c in (c
mt cc khng th IgM, IgGi, IgGs hoc IgG2). Bn cnh

mt con ng hot ho b th nh lectin MB c kh nng lin

kt vi inannoza ca b mt tc nhn gy bnh (vi khun nm
V..V..) t ko theo s hot ho b th to ra hiu qu
opsonin vi khun v loi b Ag- Ab.
2 . S hot ho b th c iu ho v kim sot bng mt tng
th cc protein iu ho, ho tan nh Cl-INH, C4bp, yu t' 1,
yu t H hoc cc th th mng t bo DAF, MCP, CRl.
3. S hot ho b th gi vai tr quan trng trong qu trnh vim
(to ra cc c t gy phn v anaphylatoxin C3a, C5a) qu
trnh opsonin ho cc vi khun (vai tr ca (C4b, C3b, Cbi,
CRl v CR3) v lm phn hu cc vi sinh vt bng phc h
tn cng mng - MAC).
4. Nhiu vi sinh vt pht trin cc bin php khc nhau to ra s
n trnh hot ng ca b th v ch c th b thc bo khi c
mt nhiu khng th c hiu.
5. S thiu ht bm sinh mt s loi b th hoc cc cht km
hm dn n mt s bnh l, cho thy r vai tr sinh hc
ca mi loi protein b th.
6 . Mt s protein khc nm trong ba h thng cn li ca huyt
tng l h tip xc, h ng mu v h tiu si huyt u c
vai tr trong c ch bo v v c ch vim ca c th.

75

Chng VI. Phn ng khng nguyn - khng th

v cc k thut ha sinh min dch

6.1. Phn ng khng nguyn - khng th

6.1.1. Cc c tinh chung ca s lin kt khng nguyn

khng th
S lin kt khng nguyn-khng th c ba c im l; phn
ng pht nhit, c tnh c hiu v thun nghch.
Phn ng pht nhit: Ngi ta xc nh khi mt v tr ca
k h n g th (paratop) k t hp vi m t ep itop ca k h n g n gu yn

tng ng l s kt hp b sung khng gian ging nh " kha v

cha kha" (hnh 6 .1 ) S lin kt c thit lp v duy tr nh
cc lc hp dn c nng lng nh (vo khong < 10 Kcal/mol) v
khng phi l lin kt cng ha tr. Cc lc lin kt Ag-Ab c
th hin l:
- Lc tnh in gia cc nhm c o o v NH 3* i din nhau ca

axit amin trong cc chui polipeptit.

- Cc lin kt hydro gia cc nguyn t
v N hoc 0
- Cc lin kt k nc gia cc axit amin k nc.
- Lc Van der Waals do s di ng ca cc in t gia hai phn
t. Lc ny tnh n s khc nhau gia cc m my in t
ca hai phn t (hnh 6 .2 ).
S lin kt gia cc khng nguyn-khng th l mt phn ng
pht nhit, gii phng ra nng lng t khong 2 n 40 Kcal/
mol. Ngi ta c th phn bit khng th "lnh" khi n kt hp
vi khng nguyn 37c v ta nhit mnh t 30 n 40
Kcal/mol. Trong khi khng th "nng" (chng hn khng th

76

chhg li Rhesus, phn ng tt 37c nhng ta nhit thp (t 2

n 10 Kcal/mol)
- Tnh c hiu ca khng th c th hin ch mt v tr
paratop ca khng th ch kt hp vi mt epitop ca khng
nguyn. Do nu ngi ta bit c mt trong hai yu t ca
phn ng khng nguyn-khng th th c .th nhn bit c
yu t th hai. Tnh cht ny c th c ng dng, rt rng
ri trong nghin cu y hc, min dch v c trong lnh vc sinh
hc rng ln. Tuy nhin tnh c hiu ca lin kt khng
nguyn-khng th (Ag-Ab) ch l tng i'mkhng tuyt i
- Tnh cht thun nghch ca .phn ng khng nguyn-khng
th c th hin ch: phc h Ag-Ab c th b phn li do
nhit, do mi trng axit (pH<3), hoc do mi trng c lc ion
cao. Do c th ra chit tch ring khng th in vitro
ngay c khi phc h Ag-Ab c hnh thnh in vivo. V d
ngi ta c th ra ch it in vitro h n g cu ca ngi m c b n h
tan huyt t min nghin cu tnh c hiu ca cc t khng
th (auto-antibodies) chng li hng cu.
/ / / / * '*
/L ;

'
chui K
V (,

} *

-nN

^ I
s x y V
h u i

Hnh 6.1: V tr lin kt ca khng th. Phn t khng nguyn

nm lt trong rnh ca v tr lin kt ca phn t khng th b
sung theo v tr khng gian (theo Roitt, Brostoff v Male, 1990)

77
Khng
nguyn

Khng th
v
Lin kt
hydro

1
'1
,

Lc tnh in

':K;~

'

11^^

>T

Lc Van der ;> /> .

' Waals
* _____

Lc ky nc

____________

H2O ra *

H n h 6.2: Cc lc ht gia cc phn t khng nguyn v khng th

6.1.2 Cc c im v cht ng v s lng ca phn

ng khng nguyn - khng th
6.I.2.I. c im v cht lng
Phn ng khng nguyn-khng th c th hin bng i lc
lin k t gi a chn g. i lc lin k t ny th h in b n g cu truc

khng gian b sung ln nhau gia epitop v paratop. S b sung

c n g ph hp th i lc lin k t k h n g n g u y n -k h n g th cng

cao. S lin kt khng nguyn-khng th l mt phn ng cn

b n g, c th b iu d in nh sau;
Ag + Ab <=> Ag - Ab + nhit lng
Hng s kt hp K=

[AgAb]

K biu hin bng nghch o ca nng 1/mol

S "ph hp" hay "thm kht" (avidity) ca mt khng th

vi m t k h n g n gu yn c h iu to iu k in n h a n h chng x u t

hin mt phn ng kt ta, hoc ngng kt. Phn ng ny ph

thuc vo h n g s k t hp, ph thuc vo h a tr ca k h n g th

78

v s' lng ca cc epitop, nhit pH v lc ion ca mi trng

phn ng. Cc iu kin trn cn c ch trong tlic
nghim.
6.1.2.2. c im v' s'lng

Vic nh lng ml khng nguyn c th thc hin c nhd

cc khng huyt thanh a ha tr (polyvalent antiserum) hoc
khng th dn dng, bng cch xy dng mt ng chun theo
nng ca dung dch khng nguyn bit. Tuy nrtin, vic
diih lng klng th Irong huyt thanh ni chung khng th
chnh xc v:
- Cc khng nguyn u c nhiu epitop khc nhau.
-- Co khng th c hiu vi mt khng nguyn hp thnh mt
h khng dng nht bao gm nhiu phn t c i lc khc
nhau

Ch ring khng th dn ling, ng nht v c tnh vt l v

ctn lin kt vi mL epitop l c th dng nh lng chnh xc
khiig nguyn. Thng thng vic nh lng khng th hoc
khng nguyn ch mang tnh cht bn nh lng. C th hi
ngi ta dng mt dung dch pha long lin tip hai ln mt chtphn ng v gi Iiguyii nng ca mt chVl phn ng b sung
Kt qu nh lng c biu hin bng nng pha lng cao
nht m d vn <ho phn ng kt ta (hoc ngng kt) dng
tnh.

6.1.3. Phn loi cc phn ng khng nguyn - khng th

Cc phtn ng khng nguyn-khng th xy ra in uitro c th
c quan st trong thc nghim. c th l phn ng kt ta
hoc ngng kl ca phc h Ag-Ab, c th l s phn hy ca vt
mang khng ngu3n (chng hn s tan huyt khi khng nguyn
mang hng cu tng tc vi khng th). Mt s phn ng Ag-Ab
c th kh iig quan s t c in vitro. K hi ngi ta s d n g cc

khng th nh du. T c th phn bit c cc kiu phn

ng Ag-Ab.
- Kiu phn ng min dch hunh quang (Immuno luorescence)
khi khng th c nh du bng mt cht mu hunh
quang.

79

Kiu phn ng min dch phng x (radio immunological reaction) khi khng th c nh du bng mt ng v phng x.
Kiu phn ng min dch enzim ELISA (Enzyme Linked Imnumo Sorbent Assay) khi mt khng th c lin kt vi mt
enzim trong xt nghim.

6.2. Cc k thut min dch

Cc k thut c s dng trong nghin cu min dch cn c
vo tnh cht ca phn ng khng nguyn-khng th dng kt
ta hay ngng kt, hoc kh nng phn ng khng nguynkhng th lin kt vi b th, phn ng khng nguyn - khng
th c nh du hay lin kt vi mt enzim nht nh. Trn c s
cl. c hng lot cc phng php xt nghim min dch c
Vng dng.

6.2.1.K thut kt ta trong mi trng lng

6.2.1.1. Xt nghim kt ta vng
y l k thut n gin nht khi ngi ta s dng mt ng
nghim nh cha mt dung dch khng nguyn y hg
nghim. Tip theo cho t t mt dung dch huyt thanh min
dch v quan st vng kt ta gia hai lp tip xc ca phc h
Ag-Ab. K thut ny vn dc s dng kim tra nhanh chng
s p ng min dch ca mt ng vt ang trong qu trnh gy
min dch hoc xc nh nhm Lancefield ca cc streptococcus. l xt nghim kt ta Lancefield.

.2.1.2. Xc nh c ca cc kt ta phc h Ag-Ab.

K thut ny thc hin rt d dng nhng cn mt my phc
tp c n gu n nh s n g bc x m nh v n sc c tru yn qua
mt ng nghim cha mt khng nguyn v mt huyt thanh
min dch tng ng. Tia sng b nhiu x cng ln th mt
kt ta cng cao. Ngi ta nh lng trong vng d tha khng
th nh mt huyt thanh cho ng cong. Ngi ta c mt

80

quang hc (OD) theo ng cong chun suy ra kt qu nh

lng.
K thut ny c nhiu ng dng, c bit l nh lng co
khng nguyn khc nhau c nng khc nhau trong cc dch
sinh hc (tnh ra mg/mol).

6.2.2. Xt nghim khuch tn mi^n dch theo Ouchterlony

Phng php ny cho php nh tnh cc phn ng khnp
nguyn-khng th trong mi trng thch agaroz. Mc ch ca
phdng php l so snh v nhn bit hai khng nguyn hoc
pht hin s c mt ca nhiu khng th trong huyt thanh. C
mt s c im kt ta khc nhau cho php quan st c cc
dng cung kt ta ca phc h Ag-Ab trong mi trng thch
rn:
- Phn ng ging nhau: nu hai khng nguyn ging nhau hoc c
cc epitop tng t. cung kt ta vi khng th c c tnh lin

tc.
- Phn ng khng ging nhau: nu hai khng nguyn khc nhau th
chng s kt hp vi hai khng th to ra cc cung kt ta bt

cho nhau.
- Phn ng ging nhau mt phn: nu hai khng th c mt epitop
chung v mt epitop ring cho mi loi th s thy mt cung kt
ta b sung to ra nhnh cho khng nguyn th hai.

6.2.3. in di min dch khuch tn (ImmunodiTusion

electrophoresis)
Khi dung dch phn tch cha mt hn hp nhiu khng
nguyn, s khuch tn kp khng nhn bit cc vt kt
ta, ngi ta phi s dng k thut in di kt hp vi khuch
tn min dch. C nhiu kiu in di khuch tn min dch nh:
phng php ca Grabar-Williams, phng php in di min
dch Rocket ca Laurell, in di pht hin min dch in situ.

81

6.2.4. Cc phng php ngng kt min dch (Inununo agglutination)

S ngng kt cng l do hnh thnh mt mng li gia cc
khng nguyn v cc khng th, cho php kt hp mt s
lng cc ht c hnh th to ra th ngng kt c th qun st
c bng mt thng. Mng li ngng kt ch c th hnh
thnh i vi cc khng th t nht c hai ha tr tr ln. Cc
khng nguyn c hnh th hu nh lun lun l a ha tr.
Phn ng ngng kt nhy hn so vi kt ta, ngha l c th
pht hin mt s lng rt nh khng th. Phn ng ngng kt
iTiin dch cng cho php bn nh lng v cho kt qu tt,
ngi ta nn pha long huyt thanh trnh cc kt qu m
tnh gi do qu d tha khng th.
Ngi ta phn bit s ngng kt ch ng hoc ngng kt
trc tip trong chnh cc phn t to hnh th mamg cc
quyt nh khng nguyn c hiu (v d hng cu, bch cu,
tiu cu, tinh trng, vi khun, trng bch cu (toxoplasme). Tri
li, s ngng kt th ng hoc ngng kt gin tip, trong
phn t to hnh ch l gi th cho mt quyt nh khng nguyn
c c nh nhn to trn b mt ca n. Ngi ta thng s
d n g cc h t bi bn g nha polystyren hoc cc vi tin h th coles-

terol. Kiu lin kt vi mt phn t thay i ty theo bn cht

ca mt khng nguyn c nh ln chng. Cc nhn t gn nh
benzidin, axit tannic, glutaraldehyt lun lun c s dng
trong phn ng ngng kt. Mt s v d p dng k thut ngng
kt min dch l;
- Xc nh nhm mu ABO ca hng cu trn lam knh.
- Nghin cu cc cht gy ngng kt lnh 4C.
- Chn on bnh do Salmonella (Salmonellose) bng phn ng
ngng kt Widal.

6.2.5 Cc phng php min dch s dng b th

K thut min dch c s tham gia ca b th c th c thc
hin khi phn ng hot ha ban u c c nh vi mt phn
on b th Clq trn mnh Fc ca mt phn t IgM hoc mt
IgG (IgGa hoc IgG.,) kt hp vi mt khng nguyn. S hot
ha phn ng c b th s dn ti s phn hy cc phn t mang
khng nguyn t bo.

82 ______________________________________________________________

6.2.5.1, K thut phn hy t bo bng b th

K thut ny c thc hin i vi t bo hng cu, s dng
nhiu nh lng b th. y hng cu cu c s dng
k t hp vi cc k h n g th c h i u trong cc i u k i n k h n g

ngng kt s c trn ln vi mi trng sinh phm xt

nghim. Cng tan hng cu (hemolysis) c nh gi sau
khi 30 pht 37c v li tm. Tip theo o mt quang hc
ca hemoglobin c gii phng ra. Ngi ta nh lng b th c
mt trong mi trng theo n v CH-50. CH-50 l k hiu hot
ng phn hy hng cu cu c lm nhy cm bng mt
loi khng th c hiu. Mt n v CH-50 l s lng b th cn
thit lm phn hy mt na s lng hng cu huyn ph.

6.2.5.2. K thut c nh b th
K thut ny ch cho php pht hin cc khng th c kh
nng hot ha b th. B th ca huyt thanh xt nghim cn
c lm bt hot t trc nhit 56c trong 30 pht. Phn
ng tip theo c thc hin theo hai giai on:
- Giai on th nht: huyt thanh xt nghim loi b b
th v cho thm 3 n v CH50 ca b th chut Cobaye
chun t trc. Nu huyt thanh cha cc khng th th s
k t hp vi m t k h n g n g u y n v c n h b th tron g thi
gian (1 gi 37C hoc 18 gi 4c v tip theo 1 gi 37C).

- Giai on hai: thm h thng hin hnh c cu thnh t

hn g cu cu k t hp vi cc Ig c h iu tron g cc iu k in
k h n g n g n g kt.

B th c c nh giai on u, ngi ta khng thy

hin tng phn hy hng cu. Tri li, nu huyt thanh xt
nghim khng cha khng th c hiu th b th cn li sn c
kh nng lm phn hy hng cu giai on hai ca phn ng.
Phn ng ny cn hai xt nghim kim tra: mt xt nghim
khng c khng nguyn v mt xt nghim khng c khng th,
ngha l cc kim tra cho phn ng khng th gii thch c khi
Iding nguyn hoc huyt thanh ch c nh ring b th.

83

6.2.6. Cc k thut min dch s dng thuc th nh du

Cc c h d n li du Lhn^ dc s dng nht l: thuc th

hunh quang (Huoro chromes) nh riuorescein, rodamin, tng

ng cho m u vn,^ chanh hoc m u cam di nh sng cc

tm hoc xanh tm. Cc cht, dnh (lu c th l ng v phng x

nh '"^1. hoc H pht ra tng ng cc bc x gam m a v beta.
(' c enzim nh photphataz kim hoc peroxidaz. c th lm bin

{li mu c chr do chig phn iy, cng dc dng rt ph bin

trong xl nghim min dcli lin kt enzim, v d k thut xt
nghim m in dch lin kL en/,iin K L IS A (E nzym e L in k e d Im m uriosorbent A ssay) c ri dng rt ph bin hin nay. cho mc
ch n h xc cao.

6.2.6.1. K th u t m in dch hunh qu an g

C c thuc th h u n h quang nh izo tio xia n a l ca fluorescein
(Iso th io cyan ate nurcHcein) cho mu hunh quang vng chanh

hoc lisamin rodamin cho mu huiih quang cam dc gn

cng hp vi mt khng nguyn. VI mt khng th hoc thng
hay gn VI an tig lo b u lin bng ce lin kt cng ha tr. C cc
dng xt nghim h u n h quang trc tip v gin tip, dng b th
kh u ch cli

- Trong xt nghim min dch hunh quang trc tip, ngi ta

dng mt khng th nh du trn mt lt ct m t ho hoc
trn mt lp t ho di trn lam kinh. Sau khi ra ch bi, lt
ct c kim tra di knh hin I'i c trang b hunh quang v
phn ng khng nguyn- khng th s c nh khu bng

vng hunh quang.

- Trong xt nghim hiinh quang gin tip, ngi ta trc tin
huyt thanh xt ngh im (cha khng th) vi mt lt ct t bo
cho khng nguyn t bo kt hp vi khng th c hiu ca
huyt thanh. Sau khi ra nhiu ln, ngi ta thm mt antiglobulin c nh du hunh (iiang v tip tc ln th hai.
Ra tiu bon v c kt qu di knh hin vi hunh quang.
- Trong k thut xt nghim hunh quang gin tip c s dng
h th khiych i, ngi ta cnn dng mt antiglobulin c
d n h b th v the hin p h ii

thoo l)a giai on:

Giai on I: m hoc f ho vi mt huyt thanh xt

nghim, sau ra loi b huyt thanh tha.

84_________________________________________^

Giai on 2: tip vi mt antiglobulin v thm b th ti

c'nh, sau ra tip.
Giai on 3: tip phc h phn ng vi khng th nh du
chng li b th C3 (Mt phn t khng th to ra s kt hp
trn t bo rt nhiu phn t C3b) Sau ra phc h phn
ng v c kt qu.

6.2.7. K thut min dch phng x

K thut ny ngy nay thng c thc hin trong pha rn;
m t tron g cc thuc th c c" n h l n m t gi th c h n g hn
nh y g in g c a m t tm nh a p olystyren (m icrotiter) tm

xenluloza hoc cc vin bi bng nha. Nguyn tc nh lng

min dch phng x l theo kiu cnh tranh. Phn ng khng
nguyn-khng th l phn ng cn bng thun nghch. Mt
k h n g n g u y n n h du k t hp vi m t k h n g th c h i u c
th c i ch b n g s d th a ca cc k h n g n g u y n t do. S

lng khng nguyn nh du nm trn khng th sau khi thm

k h n g n g u y n t do t l n gh ch vi nn g k h n g n g u y n t do

dng nh lng. nh lng mt khng nguyn trong mi

trng sin h vt, ngi ta k h n g th tng n g trong cc gin g

ca tm nha "microtiter". Khng th c hp th ln y

ging ca tm nha. Sau khi ra, ngi ta ph thm cc vng
nha k h n g ph k h n g th b n g cch vi m t m t d u n g dch
protein. Sau ra l i v th m hn hp k h n g n g u y n c n xt
n gh im vi k h n g n gu yn c n g loi c n h du
n h n g

bit trc s lng. y c s cnh tranh gia khng nguyn

cn x t n gh im v k h n g n gu yn n h du c k t hp vi
khng th. Sau khi ra ln na, ngi ta o hot ng phng x
cn li trong cc ging bng my m tia gamma. Hot ng
phng x cng yu th s lng khng nguyn cn xt nghim
cng c c nh ln khng th nhiu hn. Cn phi lm xt
n gh im k im tra vi gin g "trng" k h n g cha khng th y Vl
vi cc ging khng c mi trng xt nghim .

Nng khng th c suy on khi so snh vi ng th

chun xy dng vi dung dch khng nguyn c nng bit.
nhy ca xt nghim mc vi chc nanogram.
Trong mt s' k thut xt nghim phng x, ngi ta c th s
dng khng th c hiu nh du phng x
Ngi ta c th

85

s dng k thut xt nghim min dch phng x cnh tranh

nh lng cc cht c s' lng rt t trong cc dch sinh vt nh:
hocmon, (polipeptit, steroit) prostaglandin, cc du hiu ung th,

vitamin, IgE tng s.

6.2.8. K thut min dch lin kt enzim (ELISA)

Xt nghim min dch lin kt enzim (Enzyme Linked Immunosorbent Assay) hin nay c s dng rt ph bin trong cc
nghin cu chn on cc bnh ca ngi, ng vt v thc vt.
Nguyn tc ca phng php v c bn khng khc vi phng
php xt nghim min dch phng x. Trong phng php ny
khng th thng lin kt vi mt enzim nht nh, thng l
photphataz kim hoc peroxidaz.
- Nu xt nghim nh lng mt khng nguyn th khng th
c hiu vi n khng nh du s c gn vi gi th rn
(thng l cc ging ca tm microtiter c 96 ging bng nha
polystyren). Khng th c hiu ny c to ra chng li
phn t khng nguyn cn nghin cu. Bc th hai l thm
dung dch nghin cu cha khng nguyn lin kt vi
khng th c hiu. Bc th ba l cho thm khng th c
hiu vi khng nguyn nghin cu nhng c gn cng
hp vi mt enzim (photphataza kim hoc peroxidaza). Tip
theo, o hot enzim bit kh nng phn hy mt c cht
t khng c mu bin thnh sn phm c mu v c o
bc sng hp th thch hp. V d c cht ca enzim photphataza kim khng c mu l paranitrophenylphotphat sau
phn ng enzim s bin i thnh paranitrophenol c mu
vng chanh, c pht hin bc sng 405nm.
- Nu xt nghim nh lng mt khng th th khng nguyn
c hiu c gn trc tin vo y ging microtiter. Tip
theo cho khng th cn nghin cu vo to phc lin kt
Ag-Ab. Sau cho thm antiglobulin chhg khng th (chng
li k h n g th n gh in cu) c gn cng hp vi m t en zim v
qui trn h x t n gh im giVig trng hp trn.

86

Tm tt chng VI

1 . Phn ng lin kt gia khng nguyn v khng th l s kt

hp c tn h ch t b su n g gi a cu tr c k h n g g ia n c a m t epitop trn p h n t k h n g n g u y n v v n g tip x c t ng ng:

paratop ca phn t khng th. S lin kt ny mang tnh

ch t kh ng gian bn g cc lc lin k t k h n g cng ha tr.

2. S lin kt gia khng nguyn - khng th c 3 c im l

phn ng pht nhit, c tnh c hiu cao v thun nghch.
Tnh c hiu ca khng th l tng v khng tuyt i.
Do c th c nhng phn ng cho nhiu hoc t vi cc
khng nguyn c cu trc tng ng vi mc "ph hp"
khc nhau.
3. Cc k thut xt nghim v nh lng trong ha sinh min
dch l da vo nguyn tc tng tc c hiu gia khng
nguyn v khng th. C nhiu dng khc nhau nh; khuych
tn , n g n g k t m in dch k t hp in di m in dch, x t

nghim min dch lin kt enzim v min dch phng x.

87

Chng VII. Cc c quan v t bo ca h min

dch, bit ha v chc nng

H min dch c pht trin cao ng vt c v v chim,

chim 1/60 trng lng c th ca ngi. Cc c quan ca h
min dch c th c phn chia nh sau;

7.1. C quan ngun

C quan ngun bao gm chung cho h thng to mu. Cc t
bo ngun ca ty xng c th sinh ra hng lot dng t bo
khc nhau nh dng hng cu, dng megacarioxit, dng bch cu
ht, dng mono v i thc bo, dng t bo lympho. Ngay trong
tun th 10 ca i sng phi thai trong d con, ngi ta
nhn thy cc t bo ngun u tin trong xng cng vi s to
mu ty xng vo tun th 20 . ngi, mt phn cc t bo
ngun lympho ri ty xng i theo con ng tun hon mu
n tuyn c "luyn tp" v chn thnh cc lympho T, trong
khi mt phn khc tip tc pht trin ti ch (Xem hnh 1 .2 ,
chng I)

7.2. Cc c quan s cp
C quan s cp cn gi l c quan lympho trung ng. C quan
ny cng xut hin sm trong i sng phi thai trc khi c c
quan th cp. Qu trnh tng sinh cc t bo lympho nhng c
quan s cp c lp vi tt c cc kch thch khng nguyn. Vai
tr ca cc c quan ny l: Cho php cc t bo ngun lympho
giai on u tin c bit ha v sinh sn, c "hc tp"
dung np cc thnh phn cu trc ca bn thn c th, ngha
l hc cch nhn bit "ci bn thn".

88

7.2.1. Tuyn c (Thymus)

y l c quan lympho trung ng quan trng v l c quan
lympho - biu m c cu to t hai thy hp li. Tuyn c nm
vng trung tht trc v pha trn. S bit ha ca cc t bo
lympho din ra phn v v phn ty ca tuyn c khc bit
nhau. Trong vng v, cc t bo lympho c gi l cc t bo
tuyn c v c s* lng rt ln v c bao quanh bng cc t
bo biu m (Epithelial cell). Cc lympho phn ty <i dng c
bo tu (Medullary thymocytes) ca tuyn c b phn tn rt
nhiu so vi phn v. Qun th lympho tuyn c rt nhy cm
vi hocmon corticoit v b ph hy ti 95%. Ch c 5% lympho
bn vi hocmon ny l c th chn sinh l v c chuyn vo
tun hon mu.
Vai tr sinh l ca tuyn c c biu hin kh sm, trong i
sng phi thai ca ng vt. ng vt b ct b tuyn c s
khng c p ng min dch t bo i vi lympho T gy c hoc
lympho tham gia vo qu mn mun. Trong trng hp ny.
ng vt c th dung np mnh ghp ngoi lai khng ph hp t
chc.
Tuyn c c tc dng nh mt c quan cho php bit ha lympho T theo hai cch sau:
- Lm bin i ti ch cc lympho T cha bit ha thnh cc
lympho T c th th TCR i vi khng nguyn.
- To ra cc yu t' th dch c th gi l cc yu t'"thymosine".
thymopoetin tip tc gy nh hng ln hot ng ca lympho
T trong khu vc ph thuc tuyn c ca cc c quan lympho
ngoi vi v hon thin tin trnh bit ha cc lympho T.
7.2.2. T i Pabricius v ty xng
Ti Pabricius l mt c quan lympho biu m nm mt sau
ca l huyt ca loi chim cho php s bit ha cc t bo lympho B.
ng vt c v v ngi khng c ti ny. n nay. ngi
ta thy rng s chn ca cc t bo ngun lympho thnh t bo
lympho B c thc hin trong ty xng. Bng chng l cc t
bo pro.B v pre.B bt ngun t t bo ngun 0034"^ c nhn
ln khi tip xc vi cc t bo vch ngn v mng li ca xng

89

v tip nhn cc xitokin t nhng t bo ny cho qu Lrnh bit

ha ca chng. Cn iiif nh t ho T tuyn c, cc lympho
1?b cht mt phn ln ly xng (lo qu trnh apoptosis v b
cc i ihc bo nut. Qu trnh apo])tosis l mt c ch cht
Ihco chng trnh ca cc t bo.

7.3. Cc c quan lympho th cp

( -c c (juan lympho th c) cn gi l c quan lympho ngoi vi
liao gm cc hcli bch huyt, l lch, hch amidan hay hch
liiih nhn, cc tm Poyer (l nhng m lympho ri rc sut
chiu di ca rut, tp trung phn rut tha v phn tn cng
ca rut non.), cc m bch huyt lin kt vi nim mc (tuyn
nliy) ca ng h hp. ng tiu ho v ng tit niu.
c tnh chung ca c quan lympho th cp l pht trin chm
hn so vi c quan s cp. Cc cd quan ny tip tc chc nng
nui dng cc lyinpho T n t luyn c v lympho B n t ty
xng theo con ng tun hon mu. nhng c quan ny, cc
t bo l 3'mpho B v T biu hin c tnh chc nng ca chng
khi tip xc vi mt khng nguyn, mt s vng ca c quan
lyiTi)ho th cp, ngii ta tm thV mt s hch bch huj't c t
l)o bao quanh hnh thnh cc nang lymj)ho, trong chirn u
Ih l cc nang lympho B.

7.4. Ngun gc cc t bo ca h min dch

Mt phn ln cc t bo ca h miii (lch u c ngun gc to
mu. ch ring cc t bo lymi)ho T v B c cc th th b mt
(T('R v BCR) chu trch nhim v tnh min dch c hiu hoc
min dch thch ng trong di sng c th. Tuy nhin mt s ln
cc t bo to mu u tham gia trc tip vo vic cm ng, iu
ha v bc l p ng min dch rc hiu cng mt lc m bo
tnh min dch khng c hiu. l nhng t bo a nhn nh
bch cu trung tnh, bch cu a axt v bch cu a kim, cc t
bo mast, cc tiu cu. cc t bo dng mono v i thc bo.
Mt s t bo khng to mu cng tham gia vo qu trnh cm
ii hoc biu hin phn ng min dch nh: t bo nang phn

90 ______________________________________________________________ _

nhnh (dendritic ollicular cell) ca cc c quan bch cu ngoi

vi, cc t bo ni m. (xem hnlj 1.2, chng I)
V ngun gc, tt c cc t bo ca h min dch u xut pht
t t bo ngun bit ha lin tip to ra hai dng t bo ch
yu l:
Dng t bo bch cu sinh ra cc t bo lympho
Dng ty xng dn ti cc thc bo v cc kiu t bo to
mu khc nhau.
n nay ngi ta cho rng ch ring dng t bo NK (t bo
dit t nhin - Natural killer) l trc tip bit ha t t bo
ngun ty xng.
Nh vy cc t bo ngun ty xng c th bit ha sinh ra
hng lot cc t bo to mu khc nhau nh dng nguyn bo
hng cu sau ny to ra hng cu, dng t bo nhn khng l
(megacaryocyte) sau ny sinh ra cc tiu cu i vo mu. Cc
dng mono sau ny c th bit ha thnh cc i thc bo
(macrophage), dng t bo c ht (granulocyte) sau ny bit ha
thnh cc t bo trung tnh (chim 60 - 70% bch cu), t bo a
axt (chim 3% bch cu). Cc t bo a kim chim 1 % bch
cu, t bo mast nh khu m. Cui cng dng t bo lympho
sau ny bit ha thnh cc loi qun th lympho B v lympho T.
(xem hinh 1 .2 ).
V chc nng ca mt s' t bo thuc dng ty xng, c th
tm tt nh sau:
Cc t ho trung tnh c kh nng di chuyn p ng tn
hiu ha hng ng. Nh cc th th ca t bo nh CD35,
C D llb, CD18, th th tip nhn Fc nh CD32 v CD64 nn
ch n g c th c nh v nu t cc v t th hoc cc vi sin h v t
c op sonin ha bi b th v k h n g th. C hng c n g c th gy
tn thng m t bo trong cc phn ng m in dch bnh l nh

b th v khng th.
Cc t ho a axt c mu hng hoc khi nhum eosin cn
gi l "bch cu i toan" c chc nng gy c, c sn xut vi
s lng ln chng li s nhim bnh k sinh trng, tham ga
vo cc phn ng d ng do IgE hoc do tc ng ca c t
ngoi sinh.
Cc t ho a kim (Ba) c nhum mu bng cht mu kim
tnh, giu enzim arylsunfataz, p glucuronidaz, histamin v heparin.
Cc t bo mast (Ma) c hai dng, mt dng nh khu tt c
cc m li n k t, giu h ista m in v heparin. D n g th h a i n h

91

khu tuyn nhy rut, phi, cha nhiu th th ca IgE

(2,5x10/! t bo). C hai dng t bo Ba v Ma c th th vi
IgE c th to ra s kt t vi khng nguyn lin kt vdi IgE ko
theo vic gii phng cc cht ha gii trung gian nh cht ha
gii lipit, cc xitokin. Do cc t bo a kim v t bo mast c
vai tr quan trng trong c ch bo v chng li k sinh trng v
tham gia vo cc phn ng d ng cng vi khng th IgE.
Cc t bo dng mono v i thc bo (macrophage) bo gm
mono ca mu v i thc bo ca m. H thng t bo ny bao
gm nhiu dng: i thc bo ca phi, i thc bo m lin kt,
cc t bo Kuffer ca gan, i thc bo ca lch v m bch
huyt, i thc bo ca xng (osteoclaster), ca m thn kinh
v.v... Ngoi ra cn mt s" dng t bo khng thc bo (nonphagocyte) i km theo h thng ny nh khu cc hch bch huyt
v tuyn c (thymus).
Cc mono v i thc bo cha mt s ln cc enzim l dng
peroxidaz v lyzozim tham gia vo cc phn ng vim, to ra
hin tng dung hp t bo gia chng, t ti cc t bo khng
l, nhiu nhn (hin tng syncytium) nh cc t bo Langerhans.
S bit ha cc t bo n nhn (mono) mu thnh cc i
thc bo ca m km theo vic tip thu c tnh chc nng nh
gy c cho t bo v chc nng dit vi khun bng cch sn
xut ra cc dn xut hot ha oxy v gc nitrozil (NO).

7^. Cc t bo thuc dng lympho, bit ha v chc nng.

7.5.1. c im chung ca s bit ha cc t bo lym pho

Cc t bo lympho bao gm hai dng qun th l lympho T v
lympho B, u bt ngun t cc t bo ngun to mu (haematopoietic stem cells) c mt giai on trung gian ging nhau l t
bo ngun lympho (lymphoide stem cell) nhng cha c xc
nh r. Hai dng lympho ny khc vi cc dng t bo khc
ch c s bit ha theo hai giai on: giai on u c lp vi s
kch thch ca mi trng, giai on tip theo ca s hot ha
chu nh hng ca cc khng nguyn hoc do s tng tc idio-

92

typ. iu cho php to ra s thch ng ca p ng min dch

c hiu vi cc kch thch ca c th v ca mi trng cha
khng nguyn.
Ngi ta cn phn bit s bit ha din ra c quan trung
ng v c quan ngoi vi. i vi t bo T s bit ha xy ra
tuyn c, vi t bo B xy ra ty xng. Qu trnh bit ha
ny c tnh cht khng thun nghch, c c trng bi s sp

xp li cc gen biu hin cc th th tip nhn khng nguyn

trn mng t bo ca mi loi qun th: TCR hoc BCR. Giai
on bit ha c quan trung ng l mt qu trnh la chn
dng nh cc phn t ca MHC kt hp vi peptit ca khng

nguyn ( vi lympho T) v nh cc epitop ca khng nguyn

tng tc vi BCR (i vi lympho B). S la chn dng cho php
loi b mt phn ln cc lympho (c bit l lympbo T) v loi b
cc lympho B t phn ng. Lympho B "t phn ng" b loi b
bi v trn b mt ca chng c cha th th "cha chn mi" bao
gm chui nng IgM ghp cp vi chui nh gi X (pseudo-X).
Mt khc, mt s lympho B do c s sp xp li cc mnh gen
nn sn xut ra cc t khng th (autoantibody) chng li cc
khng nguyn ca bn thn (autoantigen) th cn phi b loi b.
C ch loi b th hin khi lympho B nhn bit cc t khng
nguyn lin kt vi t bo k bn c t khng th, s truyn

tn hiu cho t bo ny "t st" theo c ch apoptosis (l mt qu

trnh cht ca t bo lp chng trnh).
Giai on ngoi vi ca cc qu trnh bit ha xy ra cc c
quan bch huyt ngoi vi v ph thuc vo cc tn hiu ca cht
hot ha c to ra do s tng tc ca BCR vi cc epitop, v
do s tng tc ca TCR vi cc peptit lin kt vi phn t MHC.
Cc phn t khc ca mng t bo ca h min dch cng gy ra
nhng tn hiu cng ph hp cn thit cho s hot ha.
7.5.2. S bit ha ca lympho T v du hiu khng nguyn
bit h

Lympho T c bit ha t t bo tin thn ty xng CD34^,

CD44* di chuyn v tuyn c. y chng tr thnh t bo c
lp v l nhng nguyn bo sau phn chia v bc l cc phn
t khng nguyn CD2 , CDl, CD5 . Tip theo cc t bo bc l
phn t TCR, phc h CD3. Cc t bo khc bc l thm phn t

93

CD4 v CD8 . Ch CD l vit tt t ch "cm bit ha" (Cluster

of Differentiation) v con s mang theo l th t nh loi quc
t.

Qu ti'nh chn ca lympho T c Ih c tm tt theo bng

sau;
Bng 1 : Qu trnh chn ca lympho T
C c yu t

Cc

dng t bo

V tr bit ha

bit ha
T bo ngun min dch
T bo tin thn T
Cc yu t bit
ha ca tuyn
c

M to mu
Tuyn c

T bo c v

T bco c ty

Lympho T cha chn

Yu t bit ha

Lympho T chn

Mu v c quan

tuyn c

(C thm quyn min dich)

bch huyt

,
Bit ha U^p iheo chc nng
Chc nng ghi

Chc nng iu ha

Chc nng hiu

nh

(T b tr : Th v T c ch :Ts)

qu

(T ghi nh)

(T gy c : Tc
v T hiu qu
Qu mn mun)

Qu ti-nh chn la m tnh v dng tnh i vi qun th

lyinpho T cng din ra ( tuyn c v c trnh by tm tt
linh 7.1

94

T k h ith u

i vo tuyn c

P r o tiiio x it
CD4
CD8

king cha TCR

LP V

X
APOPTOSIS

chn TCR

u,p

LP TU

:CD8^

\
CMHI V^A

IH IC

-J-

,
^ p e p t it

t bo
biu m

CD4*
CHN DUONU TNH

CHN M TN
i ra vng ngoi vi, tr
thnh cc t bo lym-

pho chn, kt hp
BN NGOI TUYN c

c hiu vi MHC,
khng c c tnh t
ph<'n ng

H nh 7.1. S la chn m tnh v dng tnh ca lympho T

tuyn c. lp v cc t bo tuyn c bit ha gm c CD4* v
CD8* (la chn dng tnh), nhng ch tn ti ring cho tng
qun th ph ch bc l mt dng CD4*8 hoc CD4'8* do tc dng
loi b (la chn theo m tnh) ca cc phn t phc h MHC.
(Theo Miller, 1993).

95

7.5.3. S bit ha lympho B

Lympho B c bit ha t cc t bo ngun lympho CD34 ca
gan phi thai v t ty xng ca ngi trng thnh. S bit
ha lympho B xy ra lin lc trong i sng c th v khc vi
s bit ha ca lyinpho T hai c im:
S bit ha lympho T xy ra tuyn c v gim dn n tui
dy th.
S bit ha lympho B ca ng vt c v xy ra ty xng,
ca chim xy ra ti Pabricius. Tin trnh bit ha ca lympho
B c th tm tt nh sau: T t bo ngun ty xng bit ha
thnh lymj)ho B khi thy (pro B) sau thnh tin lympho B
(pre B) v tip theo l bit ha thnh lympho B cha chn c bc
l IgM b mt (mlgM). Giai on tip theo l lympho B chn mi
bc l IgM v IgD b mt (mlgiM v mlgD). Nu lympho B
chi khng gp khng nguyn s b phn hy. Lympho B chn
khi gp khng nguyn li tip tc c bit ha thnh nguyn
bo B (B-blaslo) v t bo plasma (plasmocyte). Ch c t bo
plasma mi c kh nng tit khng th c hiu vi khng
nguyn l. Mt khc, nguyn bo B c th tr t bo B ghi nh
(momory - B) khi gp li khng nguyn l c th nhanh chng
hnh thnh t bo trong p ng min dch dch th c hiu (s
d hnh 7.2).

96

t bo plasina

'

r ,.

e ti! C-

N guyn bo B

*
khng nguyn

-------------

-r

/*p

,
B ghi nh

rt, A

H n h 7.2. S qu trnh bit ha lympho B.

(theo J.p. Revillard, 1994)

7 .5 .4 . S b i t h a c c d n g t b o k h c t h e o c h c n n g
m i n d c h

7.5.4.1. Cc t bo d it t nhin (NK: N a tu ra l K iller)

Cc t bo dit t nhin bao gm mt qun th khc nhau ca

cc t bo bch cu c c tnh gy c. Ngoi chc nng gy c
chng cn bc l th th CD16 c i lc cao vi Fc v th th
CD56. Phn ln cc t bo NK u c hnh thi ca cc lympho
bo ln c ht LGL. Mt s trong chng li c du hiu bit ha
ca dng t bo T nh cc th th CD8 , CD2 , TCRX. Mt dng

97

th ba ca cc t bo NK khng c du hiu bit ha c trng

cho c dng t bo T v B nn c gi l t bo lympho khng c
c tnh "Null lymphocyte".
7..4.2. Cc tiu cu. (Throm bocytes)

Cc tiu cu xut pht t cc t bo nhn khng l tham gia

vo qu trnh cm mu (haemostasis) cng nh cc phn ng
vim v chng nhim trng. Chng cng bc l cc phn t lp I
ca phc h MHC, cc th th ca IgG (CD32) ca IgE (CD23),
cc th th ca yu t VIII, ca vitronectin (CD51), CD41 v
CD42; ca xitoadezin cho php lin kt i vi cc brinogen, fibronetin v vitronectin trong chc nng ng mu v cm mu.

98

vm

/ y^_j\\,ch

| ^ B ' W ..
----------- Cc tm peyer ca rut non
______ Rut tha
~f

Mch bch huyt

e f ' '

, ,

I,

Tu xdng
H nh

dang m t hach bach h u y t

'1* ' t !
' \;i' i K Y-.

Mch bch
huyt ti ...;; 7

\ .11* 1'i^/
)| |

Mch ni

' M

1 V '
\
l

) 1

lA u i

Trung

t Y

......

mm

/ \'j
\
'\

V- 1 !

\v

Lp v

n;V

/ s

'.

"v

S-'
V.

Lp cn_

vo
Mch bch
huyt i

Hnh 7.3. V tr h thng m t bo min dch ca c th ngi

7.5.4.S. Cc t bo trnh din khng nguyn (APC: Antigen

presentng cell)
T bo trnh din khng nguyn bao gm hai loi :
Trinh din khng nguyn cho lympho B l nhng t bo nang
c dng thy hoc bch tuc (dendritic cell) ca hch bch huyt,
ca lch. Chng s c nh khng nguyn trn mng t bo bng
th th ca b th C3 v trnh din cho cc t bo B. Cc khng
nguyn c th vn c lu gi lu di trong nhiu thng trn b

99

nit t bo nang c thy. Cc t bo nang c thy khng c

ngun gc to mu.
Trinh din khng nguyn cho lympho T c m bo bng i
cc cc t bo mono, di thc bo v cc dn xut ca t bo tua.
Cc khng nguyn c trnh din di dng cc peptit lin kt
vi cc phn t ca MHC lp I s trnh din cho cc t bo lympho TCD8 *. lin kt vi cc phn t ca MHC lp II s trnh din
cho cc t bo lympho TCD4"^.
0 tuyn c, cc t bo APC bao gm cc t bo biu m ca lp
v tuyn c, cc t bo tua v cc i thc bo nm gia lp v
v ty ca tuyn c. cc m t bo khc, APC l cc t bo tua
Langerhans ca biu m. Cc t bo ny khc vi cc t bo thc
bo (phagocytes) l khng c th th i vi b th v bc l cc
phn t ca CDl v CD4 hoc c cc th th vi Fc. Cc t
bo ny bt gi khng nguyn v ch bin thnh cc peptit lin
kt vi cc phn t MHC lp II, sau vn chuyn v pha vng
hch bch huyt. Cc APC cn li l cc t bo khe. Khc vi cc
t bo Langerhans, cc t bo khe rt t tng hp v i mi cc
phn t MHC lp II.
- Cc t bo c thy ca m lin kt cng c chc nng ging cc
t bo ca Langerhans.
- Cc t bo B cng tham gia trnh din khng nguyn cho t
bo T bng cch chng nhn bit khng nguyn nh BCR, sau
to phc h BCR-Ag. Phc h FCT-Ag s c nhp bo v
khng nguyn s c phn hy thnh cc peptit nh endosom. Tip theo cc peptit khng nguyn c lin kt vi cc
phn t MHC lp II gy ra s hot ha lympho T. Bn thn
Lympho T khi c hot ha nh ti'n s tng hp cc lymphokin kim sot s hot ha ca lympho B. l mi quan
h tng h trong p ng min dch qua trung gian t bo v
p ng min dch dch th.
- Cc t bo mono v di tlic bo cng bc l cc phn t MHC
lp II v trnh din khng nguyn cho cc lympho TCD4*.
- Cc t bo ni m (endothelial cell) v biu m (epithelian
Ccll) cng c th l cc APC v bc l cc phn t MHC lp II
khi c kch thch bng gamma inteferon (IFN y)

100

7.5A.4. Cc t bo lym pho T g y c. (Tc)

Cc lympho Tc nhn bit cc t bo ch (c th l nhng t

bo b nhim trng hoc virus, cc t bo ung th...) bng s
tng tc phn t gia TCR vi mt peptit kt hp vi mt
phn t ca MHC. Trong trng hp TCD8 * xy ra s tip xc
vi cc phn t MHC lp I v trng hp TCD4^ c s tng
tc vi phn t MHC lp II.
Cc t bo NK v LAK (t bo git c hot ha bng lymphokin: lymphokine activated killer cell) cng gihg nh i thc
bo khi c hot ha s ph h\ cc t bo ung th hoc t bo
gi bin dng. Ngun gc ca s ing tc c hiu ny vn cn
cha c sng t.

101

Tm tt chng VII

1 . Cc c quan ca h min dch bao gm

- C quan ngun sinh ra cc t bo to mu v cc t bo ca h

min dch
- Cc c quan trung ng hay s cp, cc c quan ngoi vi hay
th cp. T cc c quan ny cc t bo ca h min dch c
sinh ra, c luyn tp nhn bit c "ci bn thn v ci
khng phi ca bn thn" c bit ha v thc hin cc chc
nng min dch.
2 . Cc t bo tham gia vo phn ng min dch bao gm mt
phn l cc lympho T v lympho B c cc th th b mt nhn
bit khng nguyn ring cho mi qun th, v mt phn khc
l tng th cc t bo ph tr c chc nng cm ng, iu ha
v gy hiu qu min dch c hiu v khng c hiu.
Cc t bo tham gia vo phn ng min dch u bt ngun t
ty xng to mu. S bit ha ca chng c kim sot bng
tng th cc xitokin v cc yu t tng trng ph hp vi s
sinh sn v s chn ca chng.
3. Cc loi t bo a nhn trung tnh v a axit c nhng c
im khc nhau v chc nng phn bit nhau. T bo a nhn
trung tnh c i sng ngn, c chc nng kim sot s nhim
trng v cc phn ng qu mn vi s tham gia ca b th v
khng th.
4. Trong khi cc t bo a axt rt c, kim sot s nhim k
sinh trng; gy ra tn thng t bo trong cc bnh d ng.
5. Cc t bo a kim v cc t bo mast ca m lin kt v m
nim mc (tuyn nhy) tham gia vo phn ng min dch ph
thuc IgE trong cc bnh d ng v nhim k sinh trng.
6 . Cc t bo APC c vai tr rt quan trng trong p ng min
dch c hiu qua trung gian t bo. l cc APC cho lympho
B v cc loi lympho T.
7. Chc nng trnh din khng nguyn c thc hin nh nhiu
kiu t bo, gy ra hin tng thc bo, phn hy t bo v
gy c cho t bo ch.

103

Chng VIII. S tng tc gia cc t bo min

dch v iu ho p ng min dch

8.1. S tng tc gia cc t bo c thm quyn min dch

Cc t bo lympho bt ngun t cc c quan lympho s cp sau

khi c bit ho v luyn tp min dch u l nhng t bo

chn, c thm quyn min dch ngha l c chc nng min
dch nht nh. C th l chng c kh nng nhn bit mt loi
epitop nh mt th th slg (Ig b mt ca t bo B) hos nh
TCR ca t bo T c quan lympho th cp. S tip xc vi epitop ca cc t bo to ra mt giai on mi cho s chn ca cc
t bo c thm quyn min dch gip cho chng tr thnh nhng
t bo p ng min dch c hiu qu. S chn mi ca cc t bo
cn gip cho s hp tc gia cc loi t bo c thm quyn min
dch i vi nhau v cho php c th thch ng nhanh chng vi
mi trng xung quanh. C cc loi t bo tham gia vo s hp
tc trong p ng min dch t bo l:
1.Cc t bo trnh din khng nguyn (APC) l i thc bo,
thc bo n nhn, t bo dng bch tuc hay cc t bo c tua
(Dendritic Cell) v mt s loi t bo khc nh Langerhans
ca biu m, c cc t bo B. Cc APC c chc nng ch yu l
trnh din cc khng nguyn cho cc lympho T b tr (Th) v
lympho T hiu qu (Tc).
2.
Cc t bo lympho b tr T-CD4 ng vai tr cm ng gy ra
p ng min dch.
3. Cc t bo lympho T hiu qu cn gi l Tc (T gy c) c vai
tr loi b cc t bo b nhim virus hoc t bo bin dng ung
th. Tc lun lun biu hin cm bit ha CD8 *.
4. Cc t bo c thm quyn m in dch nh lym pho B (tit ra
khng th) lympho T CD8 ^ (chuyn bin thnh cc t bo gy
hiu qu tit ra lymphokin gy c) v c hai loi t bo u

104
phn chia tng cng k h i c d) ng m in dch. Bn cnh
cn c mt c ch kim st rt chnh xc gii hn s h)

lc dp ng min dch. l s km hm p ng c hiu qu

theo kiu c ch ngc (feedback), nh vai tr ca Ts
(T.suppressors).
Khi c khng nguyn xm nhp, c ch' hp tc v iu ho
p ng dng thi xy ra cho php loi b khng nguyn nhng
ng thi cng c qu trnh chp nhn khng nguyii. Tuy
nhin, s loi b khng nguyn xay ra u th (li vi cc khng
n g u y n l v s d j) n g m i n d c h b k m

hm

d c L o r a d(Vi

vi cc t kh n g nguyn (autoantigen). Ngi ta c th phn bit

hai giai on hp tc t bo l:

- Giai don cc i ihc bo bt gi khng nguyn v trnh din

]30)tit khng nguyn cho cc lynipho T b tr (Th). l s
hp tc cc i thc b<o v lym pho T b tr.
- Giai on gii phng cc yu l hot ho (lymphokin ca Th)

v hot lio cc lympho-B d tit ra khng th. l s h|)

tc gia Th v lyinpho B.

8.1.1.Hp tc di thc bo - lympho T v trnh din khng nguyn

S h|) tc cc lynipho T vi cc di thc bo, t bo mono cn
cc qu trnh sau;
- Bt gi khng nguyn ch bin thnh peptit phn t nh v
trnh din peptit khng nguyn cho cc lympho T b tr c
hiu mc cc phn t xMHC lp II.
- Nhn bit gia cc t bo nh phn t MHC lp II ca i thc
l)o v lympho T.
- Hot ho lympho T nh cc cht truyn dn sinh hc ho tan
nh L l v IL 6 do i thc bo hot ho tng hp ra.
C ch phn t v t bo ca s trnh din KN c th hin
hai dng sau i vi hai dng lympho T: TCD4 v TCD8.

Dang th nht l khng nguyn ca bn thn (khng nguyn

ni sinh) v cng l nhng khng nguyn ca virus nm bn
trong t bo cht (Cytosol) ca t bo b nhim s c ch bin

bng vi Ih proteasoine, mt phc h gm 28 tiu n v trong d

c hai tiii d(Jn v l LMP2 v LMP7 c V'ai tr tiu ho< khng
nguyn ni sinh (LMP2 v LMP7 dc m ho trong phc h gen
HLAII, xem hnh <1 .2 ). Peplit khng nguyn c ch bin s

105
c T A P l v T A P 2 vn chuyn vo khoang li ni cht lin
k t v i r n h ca H L A I mi c tng hp nhng cn nm
khoang li ni cht. Vic lin kt ca peptit khng nguyn vi
H L A I c s gip ca cc phn t bo m u C a ln e x in , Calrticulin v mt protein tr gip cho TAPI l TAPASIN. Sau
ch ring phc h HLAI - peptit khng nguyn c ng gi
bng bc mng v c vn chuyn ln b mt t bo ch b

nhim trnh din cho t bo T C D 8\ nhng t bo khng b

nhim virus ni bo, cc peptit ca protein bn thn lun lun
lp y rnh lin kt ca MHCI (HLAI) v bc l trn b mt
m ng. K h i t bo b nhim v iru s ni sinh, lng MHCI lun c
tng hp d tha sn c khoang li ni cht sn sng lm
nhim v trnh din khng nguyn nhim ni sinh (Hnh 8.1).
D a n s th h a i l khng nguyn ngoi sinh b bt gi bi cc i
thc bo v cc t bo B. Cc khng nguyn ny c nut (endocytosis) v c bc trong bc mng (vesicle), sau dung hp
vi lysosome v b tiu ha, ch bin thnh cc mnh peptit
khng nguyn trong mi trng axit ca bc mng. Trong lc ,
cc phn t MHC lp II (HLA-II) cng c tng hp trong
khoang li ni cht nhng lun lun c lin kt vi mt protein bo mu (chaperon) c tn gi l chui li. (Invariant chain).
V v y M H C II khng Ih kt hp c vi bt k protein mi
c tng hp li ni cht. Chc nng th hai ca chui li l
hng dn cho MHCII lin kt vi bc mng c pH axit cha
peptit KN cn trnh din. Phc h MHCII-Ii, sau s c tip
cn vi mt s" protease a axit v c bit di tc ng ca
HLA-DM lm phn hy, tch ri chui li ra khi MHCII d lin

kt vi peptit KN. Phc h MHCIl-peptit KN s c bc l trn

b mt mng t bo APC trnh din cho t bo TCD4*.
Cc i thc bo cng c th bt gi nhiu khng nguyn nh
cu trc kt dnh khng c hiu (v cng c th nh cc khng
th c i lc cao vi t bo), Khng nguyn b bt gi s c
ch b i n n h q u t r n h p h n g i i p ro te in n i s in h t h n h c c

mnh peptit khng nguyn nh v cc peptit khng nguyn nh

s lin kt vi cc phn t HLA lp II- v c c' nh trn b
mt t bo APC. Epitop ca khng nguyn s c nhn bit c
hiu bi mt TCR ca lympho T b tr. Mng t bo cha CD., c
c tnh nhn bit cc phn t HLA II (DR, DQ, DP). S lin kt
gia hai loi t bo (Th-i thc bo APC) cn c tng cng
bng li n kt ca cc phn t khng c h iu nh C D 2 -L F A 3 ,

106

LFAi - ICAM. (ICAM: Intercellular Adhesion Molecule v LFA:

Leukocyte P unctio n Antigen c gi l cc integrin thuc h c c
glycoprotein heterodime ca mng t bo c chc nng lm k't
dnh gia cc t bo vi nhau v gia cc t bo vi cht nin
ngoi bo). Hnh 8.2. trnh by s s trnh din khng nguyin
ngoi sin h v v a i tr ca cc cm bit ho CD 4 v CD 8.
C ch phn t v t bo ca s trnh din khng nguyn th.
hin cc c im sau:
- S tip xc gia i thc bo v Th c th quan st c c c
hch lym pho k h i c s xm nhp ca mt kh n g nguyn m c
h n h th n h cc m i thc bo hot ho bao q u a n h ciC

lympho T.
- S hp tc i thc bo-Th cng cn mt tn hiu ho hc di
dng cc cht truyn dn sinh hc nh: IL l v IL6. Ngoi rai,
cc protein ny cn c nhiu cht khc nh hocmon ACTI-i
(Adrenocorticotrophic hormone, mt hocmon kch thch tuyin
thng thn), yu t gii phng tuyn di i, lm tng gluicoz ca mu. mc lympho T, IL l gy cm ng tng hip
IL2 (l mt yu t cn thit cho s tng sinh ca cc lympho T)
cng nh to cm ng bc l cc th th ca Th i vi IL2i.
IL l cng gip cho s chn mi cc lympho B.
Cc t bo khc cng c vai tr APC l cc t bo tua bc l ciC
khng nguyn HLA lp II v khng nguyn CD6. Ngy nay',
ngi ta cho rng cc t bo tua c vai tr rt quan trng trong
cm ng v duy tr p ng min dch.
Tm li, chc nng ca cc i thc bo l trnh din khng
nguyn, nhn bit lympho T, tng hp ILl v trong cc triig

hp bnh l c th m bo vai tr ca cc t bo ho sng

(keratinocytes), t bo hnh sao (astrocytes), t bo gian mclh
(mesangial cells). iu ng ch l s trnh diti KN c tnlh
chn lc c hiu i vi hai loi t bo TCD4* v TCD 8* (H n lh
8.3)

107

____
/
M ng sinh
cht

Peptit
k h n g nguyn

_ _ v

IK> niy Goigi

Calnoxin'*

Calreticulin
Peptit

Proteasomo

H n h 8,1. S trnh din khng nguyn ni sinh

108

Khng
nguyn

1 =

i thc bo

MHCca
TB-B
TVLi
thc b^

Li ni cht

MHC-II

Hlnh 8 2 * Sd trnh din khng nguyn ngoi sinh

109

(B )
(A )

T bo c h

T bo t r n h d i n

P h n t M H C

lpl
P e p tit
- ^
kh n g nguyn r X V y V y T ^

c
c
P e p tit

CD4

V
V ^

Whnnp
khng

T h th t bo T

^
^

CD8

T y r : j V '. '

T bo T y r o z in k in a z
T CD 4*

nguyn

T h th
t bo T

r - c ,-

T y r o z in k in a z

T bo
T C D 8*

H n h 8 . 3 . V a i t r c a c c c m b i t h o C D 4 v C D 8
t r o n g t r n h d i n k h n g n g u y n

8.1.2. Hp tc lympho Th - lympho B

c im chung ca s hp tc lympho Th-lympho B l lm
cho lym pho B bin dng v c hot ho tng hp cc kh n g
th IgM hoc lympho B c th tr thnh cc t bo mang IgG,
IgA hoc IgE ca mng v bit ho tip tc thnh cc t bo
plasma sn xut cc Ig khc nhau, ng thi bin thnh cc
lympho B ghi nh min dch.
Giai on hp tc Th-B xy ra theo hai c ch c quan h cht
ch vi nhau. l hin tng c hiu khng nguyn v hin
tng khng c hiu khng nguyn, c hai hin tng ny vn

110
cn ang c bn lu n v s tn t i v bn cht ca n. Trong

c ch ny, ngi ta cho rng s c mt ca i thc bo s lm

d dng cho s hp tc gia lympho Th v lympho B. i thc
bo c th trnh din khng nguyn cho cc lympho T v cho n
mt tn hiu hot ho lm nhy cm cc cht truyn dn sinh
hc ca lympho T. S tng tc trc tip gia lympho T v lympho B xy ra ng thi vi vic nhn bit khng nguyn vi s
tham gia ca TCR v cc Ig b mt hoc HLA lp II ca lympho
B. Hin tng ny c m t di tn gi l cu khng
nguyn. Lytnpho B sau khi bt gi khng nguyn nh cc Ig b
mt c th bc l khng nguyn mc mng t bo tng t
nh mt AP. S tng tc Th-B cng c th c tng cng
bng cc phn t kt dnh nh CD4 ca lympho Th v HLA lp
II ca lymphoB. Hin tng tng tc khng c hiu khng
nguyn c s tham gia ca cc intelkin. Cc lympho Th tit ra
mt lot cc intelkin trong vi mi trng cha lympho B hot
ho t c hai hiu qu sau:
- Lm tng sinh t bo B: lymphokin ng vai tr l cc yu t'
tng trng t bo B (B cell groivth factor: BCGF) v i hi t
ho B phi c cc th thBCGP. S hot ho ny n h lL l hoc
cht kch thch phn bo (mtogen) IL2, inteferon a, v IL4 l
nhng yu t tng sinh t ho.
- Lm bit ho t bo: lymphokin lm hin i t bo B tit IgM
thnh cc t bo B tit cc Ig khc nhlgG, IgA, IgE. l cc
yu t bit ho t bo B (B cell dferentiaton factor BCDF).
Ngy nay ngi ta bit IL2 ng thi ng hai vai tr l
lm tng sinh t ho v gy ra bit ho t bo, IL4 ng vai tr
kch thch vic sn xut IgG, IgE, IL5 lm tit IgA. Inteferon Y
gy ra bit ho t bo ging tc dng ca IL6. Cc BCGF cng
tham gia km hm tng hp chui nng ca cc Ig.
S p ng min dch i vi khng nguyn c tnh cht khng
ng nht bi v cc khng nguyn c th nhiu dng khc
nhau nh: protein l dng ho tan, cc khng nguyn l nhng
t bo (l khng nguyn ph thuc tuyn c), cc hp ch'!
polime nh polixacarit ca vi khun (l khng nguyn khng
ph thuc vo tuyn c) c kh nng kch thch lympho B, khng
cn s c mt ca i thc bo v lympho T. trng hp ny
cc khng th c tit ra ch yu l IgM.

111

S hp tc gia lympho Th v mt lympho T khc cng c th

lm bin i lympho T ny thnh dng c hiu qu, c kh nng
gy ra p ng min dch trc tip di vi mt khng nguyn
c a lp li vo c th. Cc lympho T c hiu qu ny c th
chuyn bin thnh cc dng lympho Tc, hoc thnh lympho T
tit c c lymphokin.

8.2. S iu ho p ng min dch

Mt khng nguyn l khi xm nhp vo c th s gy ra p
ng min dch dch th (sn xut ra cc khng th) v p ng
min dch qua trung gian t bo.
T lu. ngi ta bit rt r kho d tr ca h min dch rt
a dng v c th thch ng vi bt k mt khng nguyn no.
M t con th hoc mt con chut c kh nng tng hp ra cc
khng th khng ch chng li cc virus v/hoc vi khun c mt
trong mt sinh thi m cn chng li tt c cc phn t protein
c cu trc rt khc nhau nh anbumin, insulin ca nhiu ngun
gc kh c n h au hoc thm ch mt cht mi c tng hp
phng th nghim khng tn ti trong t nhin.
C ch no c th gii thch cho kh nng sn xut ra cc loi
protein b sung cho cu trc ca khng nguyn l rt phong ph
d? c nhiu gi thuyt gii thch cho c ch iu ho dp ng
min dch. Ngi ta cho rng p rg min dch c biu hin
ba dng; iu ho p ng min dch th dch, tc l iu ho
vic sn xut cc khng th ho tan, iu ho p ng min dch
qua trung gian t bo v cui cng l kh nng iu ho nh s
tng tc min dch thn kinh - ni tit vi s tham gia ca
nhiu loi hocmon v cc cht dn truyn xung thn kinh.

112

8.2.1. iu ho p ng min dch bng cc khng th v

mng li idiotip
8.2.1.1. Khng th i lc cao hay khng th bao vy

Cc khng th c sn xut ra t lympho B c th thay i

trong p ng min dch th dch. Tht vy, lc u, khi mt
khng nguyn l xm nhp, ch xut hin mt s t cc lympho B
nhy cm vi khng nguyn . Dn dn s p ng min dch
tng ln do tng sinh mt dng t bo B v lm bin i khng
nguyn l. Sau t lu c s cnh tranh kt hp vi khng
nguyn lm xut hin kh nng chn lc ch mt dng t bo B
Cc khng th i lc cao ch c sn xut ra t mt dng t bo
B. Khi c khng nguyn l xn nhp tr li th chnh khng th
c i lc cao s kt hp nhanh chng vi khng nguyn v cnh
tranh vi cc th th cng loi ca lympho B. Cc khng th )
lc cao vi khng nguyn l c gi l cc khng th bao vy
hay khng th phong b Tc dng iu ho p ng min dch
th dch s to ra hin tng Khng cn ti kch thch h thng
min dch. Nh kh nng n \y trong thc t, ngi ta ng
dng khng th bao vy ha mt s bnh nh tan huyt tr
s sinh (liu php huyt th 'ih anti-Rh(D) hoc liu php huyt
thanh khng un vn v.v...
mt kha cnh no , cc khng th i lc cao li c tc
dng tiu cc, c th che ph cc t bo bin dng ung th, ngn
cn khng cho cc lympho T ?y c cho nhng t bo ny. Bn
cnh , mt s' loi khng tli i lc cao c th ngn nga kh
nng thi b cc mnh ghp t bo, cng o th c ng dng trong
k thut cy ghp m t bo.
8.2.1.2. Khng thizotip

S iu ho p ng min dch th dch ng ch l iu ho

tit khng th izotip: Trong c th, t l cc lp Ig mt con s
tng i n nh. Trong trn^ hp bnh l, nh bnh u tu, ch
mt dng Ig n dng c sn xut ra km theo vic gim tng
hp cc Ig ca cng mt izotip. Mt izotip l s khc bit cu
trc ca cc vng khng bin i cc chui peptit cu to rin
Ig, m bo cho s a dng h cu trc ca cc lp, cc di lp
v cc kiu Ig. Tt c cc izotip ca cc Ig u c mt mt c

113

th bnh thng ca cng mt loi. S iu ho izotip c

nghin cu r trong ti ing hp IgE do cc t bo T c th th
ca IgE chi phi (RKcc). Cc lymi)h() Te tng hp cc yu t lin
kt vi IgE (IgE binding Pactor; IgEBP) hoc lm tng tng hp
IgE hoc km hm tng hp IgE.
8.2.1.3. Id io tip v m ng li

iu ho khng th theo kiu idiotip v mng li c

hnh thnh t cc thc nghim ca H. Kunkel (1963), J. Oudin
v sau c N.K. Jerne (1974) tp hp li thnh quan nim
chung cho rng mi mt khng th Abl hoc mt th th T c
c trng bng mt paratop (Pi) b sung cho mt epitop (e) v b
sung cho cc epitop nm cc phn bin i ca phn t khng
th v c gi l cc idiotop (i|). Mi idiotop ii tng ng vi mt
paratop (P2 anti i|) c mt trn mt khng th Ab.^ (hoc mt th
th T). Bn thn Abv li c cc idiotip 12 c nhn bit bi cc
paratop (Pa anti iv) ca khng th Abj v.v... chnh l dy mng
li idiotop. S p ng min dch ko theo lm gim khng
nguyn xm nhp v lm tng khng th A b c nhn bit
bng mt khng th Ab.) (anti idiotip). Dn dn epitop lin kt
vi t bo sn xut Ab| s khng cn na (khng nguyn gim)
nhng khng th anti-idiotip li tng (Aba tng). Cc t bo sn
xut Abj b c' nh bi Ab, s lm ngng vic sn xut Ab|. Do
Ab., c tc dng iu ho vic sn xut Ab,. Nu tip tc tim
khng nguyn s lm tng tiu th Ab| v do ti kch thch
cc t bo sn xut khng th ny s lm ph v trng thi cn
bng, li cu"n theo vic sn xu"t Ab| v tip theo l Ab.. v t
ti trng thi cn bng mi.
S tng tc idiotip-paratop hnh thnh nn mt mng li
thng tin phn t v t bo, ng thi to ra kh nng iu ho
gia cc yu t' ca h thng min dch vi cc epitop ca cc
khng nguyn ca bn thn v khng nguyn l. L thuyt ny
biu hin r l mt trong nhng pht trin phong ph nht
ca lnh vc min dch hc v y hc.

114

8.2.2. iu ho p ng min dch nh cc t bo lympho T

Ngi ta phn bit nhiu kiu lympho T km hm hay trn p

tng tc gia chng vi nhau, cc lympho T km hm c hiu

khng nguyn v khng c hiu khng nguyn.
8.2.2.1. Cc lym pho T trn p c hiu k h n g nguyn

S hot ho cc lympho T c ch c hiu khng nguyn d

c nghin cu chut nh sau:
i thc bo cha cc phn t MHC lp II gi l IJ (tn hiu
nhn bit km hm) lm hot ho mt T km hm khc cng
cha u . Lympho T km hm TS, ny c gi l lympho T c ch
cm ng (induccr). TS| tip tc hot ho TS cng mang tn hiu
IJ^ v TS., c gi l TS^ truyn dn (transducer). TS2 tip tc
hot ho TS;; v TS , dc gi l t bo gy hiu qu iu ho T o
ch. S tihn bit gia cc t bo trong qu trnh hot ho ny
ca cc t bo T c ch s dic dm bo bng tn hiu u do MHC
lp II m ho. Trong klii s nhn bit c hiu khng nguyn
s c m bo bng cc th th khng nguyn ca cc t bo T
c ch. C th l TS, e mt idiotip, TS2 c mt anti idiotip, TS;i
c th c anti-anliidiotip. Do d, s iu ho c th c kim
sot bng t bo TS c anti-irliotip c kh nng bao vy cc t
bo T b Lr v cc t bo T gy hiu qu. Bng s kt hp gia
antiidiotip vi cc i d i o t i p . lympho TS;, s kim sot hot ng ca
cc t bo c cng idiotip vi n c lin quan n p ng min
dch bng mt o ch cnh tranh gia cc t bo c cng mt
khng nguyn hoc bng tc dng ca mt yu t" c km hm
de hiu (lo chng tit ra.
Theo Dorf v Bcna(orraf, c th cic i thc bo cn thit cho
s hot ho cc lympho T c ch trong khi trnh din khn^
nguyn.
s.2.2.2. Cc lym pho T c c h khng dc hiu k h n g nguyn

C nhiu loi lympho T km hm biu hin hot ng khn

c hiu i vi khng nguyn. Cc lympho ny c th c hot
ho bng cc tn hiu khc nhau nh ConA, histamin, cc prostaglandii D., (PGE.j). v mt s phc h min dch khc. Cc t
bo T-km hm khng dc hiu khi c hot ho bng ConA s
tit ra mt yvi t ho tan gi l SIRS (Soluble Immune Respons

115

Suppressor). Yu t km hm p ng min dch ny sau khi

c ci bin nh i thc bo s c kh nng hot ho dy

chuyn cc lympho T km hm dng c hiu. Yu t" ny cng
ng vai tr quan trng, lm xut hin cc quyt nh khng
nguyn IJ trn mng i thc bo. Cui cng rt c th hot
ng ca cc lympho T c ch c kim sot trc tip bng cc
lympho T-gy hiu qu.

8.2.3. iu ho p ng min dch bng kim tra d i truyn

Cc thc nghim u tin ca Benacerraf v cng s (1974)
chng minh s iu ho p ng min dch c kim tra bng

cc yu t di truyn. Vic s dng cc dng chut cng ngun gc

gen (chut cobaye ng sinh) cho php xc nh chc chn s tn
ti ca mt gen hoc mt nhm gen lin quan vi s p ng
min dch. Cc gen ny c k hiu l Ir (Immune response
gens). Sau ny, ngi ta chng minh cc gen Ir lin quan vi
MHC v s kim tra di truyn i vi p ng min dch ch yu
lin quan vi cc lympho T. Cc protein do Ir m ho ch c
bc l cc t bo ca h min dch nh: cc lympho, cc i thc
bo, cc t bo c tua v.v... l nhng t bo biu hin cc phn
t MHC lp II. Nhiu nghin cu chng minh cc t bo T v
B tng tc ti u vi nhau ch khi chng l nhng t bo biu
hin cc protein lp II ca MHC. Chc nng ca cc protein ny

l gip cho cc t bo T nhn bit khng nguyn.

Ngi ta cng cho rng c mt s gen khc khng lin kt vi
locus ca MHC nhng cng c kh nng iu ho p ng min
dch. Chng hn, thiu cc gen cu trc m ho cho cc th th T
hoc B, c th xy ra hin tng biu hin kiu hnh khng p
ng min dch. Mt s nghin cu khc cng cho php xc nhn

cc gen c lp vi MHC to ra s nhy cm vi mt s bnh

truyn nhim. Tuy nhin c ch tc ng ca nhng gen ny vn

cha c chng minh r rng.

116

8.2.4. iu ho dp ng min dch nh s tng tc tnin

dich-thn k in h ni ti t
8.2.4.I. Vai tr h thng thn kinh

Trong c th, h min dch cng chu nh hng tc ng ca

h thn kinh ni tit (hnh 8.4)
H thn kinh c th thc hin vic kim sot h thVig min
dch nh trc thn kinh di i - tuyn yn.
Tn hiu nhn thc

Cht truyn
dn thn kinh,
cc peptit thn
kinh v cc
hocmon

Intelkin, xitokin
v khng th

Hnh 8.4 S tng qut s tng tc min dch

thn kinh ni tict
Tuyn di i kim tra trc tip vic bi tit cc hocmon tin
yn nh hocmon sinh trng hoc prolactin, hoc c nh hng
n cc tuyn ch th cp nh v thng thn, tuyn gip,
tuyn sinh dc. Nh thu sau ca tuyn yn, cc dy thn kinh
di i gii phng trc tip cc hocmon vazopresin v oxitoxin
i vo dng mu. C th nu mt s v d in hnh v s km
hm cc chc nng min dch thng qua vic s dng cc hocmn
glycocorticoit. Cng tng t, nu mt s cn bng gia estrogen-progesteron s c kh nng gy ra cc bnh t min, lm
thay i tnh phn ng min dch trong mt s giai on sng
nh thi k thai nghn v sn ph.

117

Cc nghin cu gii phu thn kinh cho thy ton b cc c

quan lympho th cp nh tuyn c, lch, hch bch huyt, cc
m peyer u c cc dy thn kinh giao cm v i giao cm
(parasympathic) dn ti hoc tip xc vi cc t bo biu m
tuyn c hoc trc tip tip xc vi cc t bo lympho. Chc
nng chnh xc ca cc h thng mng li thn kinh khng ch
tham gia vo vic kim tra tc dng mu trong cc m t bo,
s lu hnh ca cc lympho, s bi tit cc yu t iu ho min
dch m cn c vai tr i vi s bit ho cc t bo lympho.
Cc th th ca colin v adrenalin (dng P) c xc nh
trn b mt cc t bo tuyn c (thymocytes) v cc lympho T
hot ho. Cc cht hip ng tc dng cht ng vn dc hc
(pharmacological agonistes) kiu p adrenalin, thng qua AMP
vng, c tc dng km hm s sinh sn t bo lympho v s hot
ho chng, c bit km hm s bc l th th i vi IL-2.
8.2.4.2. Vai tr ca cc cht thn knh ni tit khuch tn

Vic pht hin cc peptit trong cc nron v cc t bo khc

nhau c chc nng ni tit dn n mt khi nim v cht
ni tit khuch tn. l cc neuropeptit hoc mt s enzim
ca t bo thn kinh nh enolaz, mt s protein kt hp cc ht
tit nh cromogranin, hp cht tasikinin (tachykinine) cn gi l
cht p ph bin trong h thn kinh trung ng ngoi vi phc h
gangliozit ca mng, mt s hocmon nh oxitoxin, vazoprexin,
nrophixin, P-endophin.
Cc nghin cu mi y chng minh c tnh kch thch
min dch ca cht p vi s smh sn ca cc t bo T, 'i vi
s thoi bin cc ht (degranulation) trong t bo mast, kch
thch sn xut IL l v yu t hoi t ung th (TNF) ca cc i
thc bo. Trn mng t bo ca cc t bo T b tr v T gy c,
ngi ta pht hin c cc th th c hiu khng gian i vi
cht p. Vic pht hin ra hm lng cao ca tasikinin ti hot
dch khp c b vim gi vai tr quan trng ca peptit ny trong
bnh thp khp.
Ngi ta cng xc nhn ngui c s tng hp ti ch cc
hocmon oxitoxin v vazoprexin tuyn c khi tm ra ARN thng
tin m ho cho cc hocmon trn c mt dch chit ca tuyn.
Rt c th hai hocmon ny l cc yu t' quan trng tham gia vo
giai on hot ho sm ca qu tr '-h bit ho cc lympho T.

118

Ngi ta cng pht hin c nhiu th th nhn bit cc

hocmon sinh trng nh IGFi v IGP (yu t sinh trng ging
insulin: Insulin like Growth Factor) mng t bo lympho T
hot ho. Hn na cc ARN thng tin m ho cho cc IGFi v
IGPa cng c pht hin tuyn c phi thai cho thy cc yu.
t sinh trng c tng hp ti ch c quan min dch v
chng c vai tr quan trng trong s bit ho v chn t bo T.
8.2.4.3. Tc ng kim sot ngc ca s tng tc min
dch ni tit '

Cc IL i c kh nng hot ho trc thn kinh ni tit di i tuyn yn - tuyn thng thn trong qu trnh tit CRF (corticotrophic releasing actor) tuyn di i v tit AC1'Hl
(Adrenocorticotrophic hormone) tuyn tin yn. IL l cng kchi
thch s tit hocmon tirotrophin, hocmon sinh trng v hocmon
LH (hocmon kch thch t bo k pht trin to ra hocmon sinhi
dc).
Cc hocmon ACTH, p endophin cng c th c tng hp c3
trong mt s t bo lympho di dng cc dn xut peptit cai
chng.
Tm l i, s iu ho hot ng sng ca c th sin h v t b(C

cao ph thuc vo s cn bng v s phi hp cht ch gia ha.i

h thng thng tin gia cc t bo l h thn kinh ni ti t v hf
min dch. Trong qu trnh tin ho, mt s' cc peptit c hoiL
tnh sinh hc c la chn l nhng vecto ca s truyn tin
gia cc t bo. Hn na cc peptit tin thn cng c th b cit
ra thnh cc mnh peptit khc nhau v mt s chng c tc dng
sinh hc ngc li. C ch ny cho php tng cng kh nng
thng tin ca mt genom, bi v ch mt gen cng c the tr(
thnh mt dn v m ho cho nhng tn hiu thng tin khtc
nhau.

119

Tm tt chng VIII

1. S tng tc gia cc t bo c thm quyn min dch c

thc hin bng cc loi t bo l cc APC, cc t bo lympho T
b tr (T||). cc lympho T gy c (T-CDS"^) v cc lympho B.
Mi kiu t bo u c chc nng min dch ring bit v hp
tc vi nhau thng qua cc phn t MHC lp II gia t bo b
tr c hiu v i thc bo.
2. Ngi ta phn bit hai giai on hp tc ca cc t bo c
thm quyn min dch l: giai on hp tc i thc bo v cc
lympho T b tr v giai on hp tc gia lympho T b tr v lympho B.

s. S iu ho p ng min dch c th c thc hin bng cc

khng th theo con ng to ra cc khng th c i lc cao vi
khng nguyn hay khng th bao vy, hnh thnh cc dng
izotip ca khng th v c bit l theo c ch idiotip v mng
li idiotip.
4. iu ho p ng min dch theo con ng s dng cc t bo
T-c ch c hiu khng nguyn v khng c hiu khng
nguyn cng c thc hin thng qua cc phn t lp II ca
MHC ( ngi l HLA) nh tn hiu u c hiu nhn bit km
hm ca lympho T-km hm, hoc bng cc tn hiu ho hc
khng c hiu nh histamin, prostaglandin Ea v.v...
5. iu ho p ng min dch lun lun c kim tra v di
truyn ca cc gen Ir m ho cho cc phn t protein lp II
ca MHC cc lympho T.
6 . iu ho p ng min dch ph thuc vo s tng tc gia
hai h thn kinh ni tit (cc hocmon, cc cht dn truyn
thn kiiih) ln cc chc nng ca h min dch v tc ng
ngc chiu ca cc cht iu bin min dch nh IL l, xitokin ln
h thng thn kinh ni tit.

121

Chng IX. Min dch bnh l qu mn

9.1. Khi nim chung v min dch bnh

H min dch ca mt c th p ng li vi cng mt khng
nguyn ln tip xc th hai thng mnh hn rt nhiu so vi
tip xc ln u. p ng ny mang tnh c hiu nhng c th
din ra qu mc v a n s tn thng nghim trng cc m
t bo. S p ng min dch qu mc thng c gi l hin
tng qu mn cm (Hypersensibility), hay qu mn, nu nh
khng nguyn l c s lng qu ln hoc s p ng min dch
t bo v th dch qu mnh. Cooms v Gell phn bit 4 kiu
qu mn, nhng Roitt v cc cng s a thm mt khi nim
qu mn th 5. Nm kiu qu mn l:
- Kiu 1, qu mn phn v (Anaphylactic hypersensibility)
- Kiu 2, qu mn gy c t ho (Cytotoxic hypersensibilty)
~ Kiu 3, qu mn do cc phc h min dch (Immunocomplex
hypersensbility).
- Kiu 4, qu mn qua trung gian t 6do, hay qu mn mun
(Delayed type hypersensibility)
- Kiu 5, qu mn do kch thch (Stmulating hypersensibility).

Bn cnh hin tng qu mn, min dch bnh l cn cp

ti cc kha cnh min dch ca cc bnh t min, min dch
chng nhim trng vi khun v virus, s thiu ht ca bnh suy
gim min dch mc phi (AIDS) v min dch chng ung th,
tng sinh min dch. Sau y chng ta ln lt xt n cc kha
cnh min dch bnh l ni trn.

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9.2. Cc hin tng qu mn

9.2.1.Qu mn phn v do IgE

Thut ng phn v (anaphylaxis) ln u tin Richet v Por
tier (1902) nu ra khi h tim chng cho ch mt loi dch chir
t xc tu ca loi hi qu. Vic tim nhc li ln th hai thnj.:
lm cho ch b cht khi con vt b sc phn v (anaphylacLic
shock). Sau ny Von Pirquet (1907) nu ra thut ng d ng:
(Allergy) ch t't c cc hin tng bin i ca vt ch klii
tip xc ln th hai vi cng mt khng nguyn. Thut ng di
ng tr nn ng ngha vi qu mn cm (hypersensibility)
Ty theo cc loi ng vt, sc phn v c th gy ra try tirrii
mch v cn co tht ph qun, lm ngt th v dn n t vori.
Trong trng hp ny, trnh ci cht t ngt, ngi ta c th'
tim vo tnh mch adrenalin (epinephrin) ngn s co c trn,
v chng li s gin mch. Hin tng phn v cng biu hin:
di da dng ban nga hoc ni my ay tc th do s giiv
mao mch v tch ly hng cu di da.
C ch ca cc phn ng qu mn IgE l cc khng th tham
gia cc phn ng qu mn ngi ch yu do IgE, c th troig
mt s trng hp c thm IgG4. Cc IgE s c' nh vo cc th
th c i lc cc l RFceI c mt rt nhiu cc t bo mast v
a kim v cc th th c i lc yu hn l RFceII (hoc CD23)
ca cc t bo a axt, ca tiu cu v cc i thc bo.
Nng IgE trong huyt tng kh thp (100 -- 200 ng/ml hoc
50-100 n v quc t) v c i sng ngn khong 2-3 ngy. Tuy
nhin cc IgE ny c th ln ti lu di nhiu thng khi c c
nh trn cc th th i lc cao ca t bo mast. Cc khng
nguyn gy d ng (gi l allergene) lt qua da hoc tip xc vi
mng nhy c th to cu ni lin kt gia cc IgE c' nh
sn trn th th mng v lm hot ha t bo mast. Nh vy
nh to thnh cu n gia cc th th qua trung gian IgE, cc t
bo mast c hot ha v phn hy cc ht trong t bo, gii
phng ra cc cht ha gii trung gian, c bit l histamin. Cc
t bo mast tham gia vo qu trnh qu mn do IgE l nhng t
bo m lin kt v mng nhy. Lympho T cng c tc dng
kim sot ton b phn ng qu mn kiu I (typ H l) thng qua

123

cc xitokin gy vim ca chng. Mt khc, lympho T c

hot ha s sn xut cc yu t gii phng histamin. Cc t bo
a axit cng b hp dn n ni phn ng d ng nh cc yu t
hot ha tiu cu PAF (Platelet Activating Pactor), cc xitokin
IL-5, IL-3 c sn xut t cc lympho. Cc t bo trung tnh
cng c hp dn vo v tr phn ng nh cc intelkin IL 8 ,
LTB4, c bit cc i thc bo cng c kh nng c nh IgE
nh th th RPcelI v RFceI ca chng v s tit ra cc cht ha
gii lin kt vi khng nguyn gy d ng.
Cc cht ha gii tham gia vo qu mn phn v quan trng
nht l histamin c nh vo u mt dy thn kinh gy ra s co
c trn ph qun, rut, d con, vch thnh mch mu lm tng
tnh thm mch mu, gy ph n v gy phn ng my ay
trong da, gy tit nc nhy qu mc ph qun.
Seretonin cng c hiu qu hot ha mch mu tng t nh
histamin v c mt tiu cu nhng khng c t bo mast. Vai
tr ca n i vi phn ng qu mn yu hn so vi histamin.
Cc yu t" ha hng ng t bo trung tnh cng nh yu t
hoi t ung th a (TNFa) cng c vai tr i vi t bo mast ca
mng nhy. Mt s yu t' ha gii c ngun gc mng t bo nh
yu t hot ha tiu cu (PAF - axete), cht chuyn ha ca axit
arachionic c phn chia thnh prostaglanin (PGD2 c
trng cho t bo mast). Mt s" cht ha gii c tit ra mun
hn l IL-3, IL-4, IL-5 v TNFa (tumor necrosis actor).

9.2.2. Qu mn c hiu kiu II v III do IgM v IgG

Hai kiu qu mn ny u s dng cc khng th IgM v IgG
gy tn thng cc t bo v cc m t bo khi cc khng th ny
lin kt c hiu khng nguyn, lm hot ha h thng b th v
tng tc vi cc th th ca Fc.
Hin tng qu mn kiu II bao gm phn ng ca cc khng
th chng li mt khng nguyn t nhin hoc mt cht ngoi lai
(exogene) c' nh trn b mt mt t bo ch hoc mt m t
bo. Phn ng lin kt khng nguyn-khng th (Ag-Ab) ny li
ko mt phn ln cc t bo mu tham gia vo phn hy t bo
ch v bng c ch hot ha b th v s dng phc h tn cng
mng t bo hoc bng qu trnh opsonin ha to iu kin hp

124

dn cc i thc bo tiu ha t bo ch. l c ch qu mn

gy c t bo.
hin tng qu mn kiu III, s hnh thnh phc h Ag-Al)
c th gy tn thng v tr hnh thnh nn chng hoc phc h
ny tun hon trong mu v bm vo thnh mch mu to ra
nhiu dng bnh l do cc phc h min dch Ag-Ab v ni chung
u gy tn thng m t bo (vim mch v vim tiu cu thn
chng hn). l phn ng Arthus.
9.2.2.1. C ch ca hin tng qu mn kiu I I v I I I

l phc h khng nguyn - khng th (do IgM, IgG l hoe

IgG3) hot ha b th theo con ng c in hnh thnh
phc h tn cng mng. Cc t bo ch tip theo s b ph hy
bng s hoi t v b i thc bo tiu ha. Cc phn ng qu
mn kiu II v III c th xy ra vi mt s lng nh khng Ih
IgM hnh thnh lin kt vi Clq. T bo hng cu rt nhy
cm vi kiu phn ng ny nhng cc t bo c nhn thch hj)
vi c ch c s tham gia ca phc h tn cng mng.
S hot ha b th cng ko theo s opsonin ha cc t bo
ch nh cc thnh phn b th C3b v C3bi. Cc t bo hnt
cu v tiu cu b opsonin ha cng b i thc bo vng ty
l lch, gan v phi tiu ha.
9.2.2.2. Cc bnh lin quan n qu mn kiu I I ngi
9.2.2.2.I. Cc p h n ng truyn m u ca nhm A B O

Nm 1900, Landsteiner pht hin ra ngi c 4 loi nhm

mu ch y'u l A, B, 0, AB. S khc nhau gia cc nhm mu l
do cc khng th c trong huyt thanh v khng nguyn nm
trn mng hng cu ca mi nhm mu qui nh v c th c
trnh by theo bng 9.1. T kh nng cho v nhn ca cc
nhm mu c trnh by sd di y (S v di)

125

Bng 9.1; T h n h

p h n k h n g n g u y n v k h n g th c a

c c n h m m u A B O v n g u y n t c ch o v n h n m u

Nhm
mu

Khng
nguyn
mng hng
cu

Khng th trong
huyt thanh

Kh nng Kh nng
cho
nhn

K h n g th ch V ig B

A, A B

A, 0

13

K h n g th ch n g A

B, A B

B, 0

AB

A v B

K h n g c k h n g t h

AB

A, B, 0 ,
AB

K h n g c

Khng
v B

th

ch V ig

A A,

B,

AB,

V di truyn hc h thng nhm mu ABO c locus gen nm

nhim sc th s 9 v c lp vi cc locus ca cc h thng khc.
H ABO bao gm ba kiu ln cc alen l A, B v o . Cc gen A, B
ng tri, cn gen 0 th v nh hnh.
V c tnh min dch v ha sinh ca nhm mu ABO, ngi
ta thy nu ch c hai khng nguyn A v B th kiu hnh ca
hng cu s c 4 loi l A, B, AB v 0 ty theo c th c hoc
khng c cc khng nguyn A v B. Cc t bo hng cu rt giu
s lng cc v tr khng nguyn A hoc B trn mng (t 300.000
n 1.000.000 v tr trn mt t bo). Cc khng nguyn ny
cng c tm thy mc bch cu, tiu cu v nhiu c quan
nh da, thn, tuyn nc bt, d dy v.v... Do h thng nhm
mu cn c vai tr quan trng trong vic cy ghp cc c quan,
c bit l da v thn. Thc t, h ABO cn phc tp hn bi v
c ti hai dng gen A: gen A, xc nh khng nguyn A|, gen A,
ch xc nh ring cho khng nguyn A vi mt s lng v tr
khng nguyn A c trn mng kh nh (ch khong 300.000 v
tr cho mt t bo hng cu). Trong khi , gen A) xc nh cho
mt s' lng ln cc v tr khng nguyn trn mng ln hn
nhiu (1 .000 .000 /t bo hng cu). H nhm mu ABO cn lin
quan cht vi h thng khc ca hng cu l Rh. Cc gen ca hai
h nm 2 locus khc nhau, trn hai loi nhim sc th khc

nhau. Do trong nhm mu o mc d khng c khng nguyn

A v khng nguyn B trn mng hng cu nhng vn c khng

126

nguyn H. C th tm tt s tng hp cc khng nguyn ca

nhm mu ABH nh sau:
1/

Gal NAc (p 1,3) - Gal(P 1,3) - Glu NAc(P 1,3)-Gal

(Hoc p 1,4)
Ch't tin thn khng nguyn nhm mu
Gen H (fucosyl transferaza)
Cht tin thn nhm mu + Fucoza---------Khng nguyn H

2/ Khng nguyn H

------ >

Khng nguyn H lin kt vi

+ (al-3) GalNAc
(al-3) GalNAc
Gen A (N-axetylgalactozamil-transferaza) Khng nguyn A

3/ Khng nguyn H ------ >

+(al-3) Gal
Gen B (galactozamil transferaza)

Khng nguyn H lin kt vi

(al-3) Gal
Khng nguyn B

4/ Trong c th c khng nguyn A v B u c hai enzim ca A v B

cng hot ng.
Khi truyn mu, nu c khng th ngoi lai (alloantibody) c
th gy ra s tan huyt v ngng kt hng cu. Triu chng
bnh th hin l gy st, cao huyt p, au tht lng v kh th,
gy nn ma. S phn hy t bo hng cu (hemolysis) l do qu
trnh opsonin ha hng cu c s tham gia ca b th theo con
ng hot ha c in v c tc ng ca i thc bo vng
lch. Tuy nhin, nh cc quy tc an ton truyn mu, cc ri ro
trn c th khc phc d dng.
9.22.2.2. B nh tan m u do khng p h hp kh n g nguyn R hesus

Nu ngi cha mang khng nguyn Rhesus (Rh*) trn mng

hng cu, ngi m khng c khng nguyn ny (Rh ) th a con
ca h c Rh*. Khi mu ca thai nhi c dp chuyn sang mu ca
ngi m ln mang thai u tin s gy ra phn ng min dch
to khng th c th m chng li hng cu ca mu thai nhi (Rh*,
hoc yu 1 D). ln mang thai sau, khng th IgG chng yu t'

127

D s xut hin vt qua hng ro nhau thai gy ra s phn hy

hng cu ca thai nhi.
Bin php phng tr bt buc l tim khng th anti-D cho cc
ph n Rh trc khi c thai mang Rh^. Khng th ny s
opsonin ha hng cu ca thai tun hon trong mu m v s
gy ra s loi b chng nhanh chng khi mu ca m v khng
gy cm ng tng hp khng th IgG anti-D.

9.2.3. Qu mn tru n g gian t bo hay qu mn mun

Qu mn mun (kiu 4) c Gell v Coombs phn loi l do
vic sn xut ra lymphokin ca lympho T c hiu vi mt khng
nguyn gy ra s di chuyn, hot ha v tch ly ti ch cc
bch cu n nhn.
Ngi ta ni m in dch qua trung gian t bo hoc qu mn
qua tru n g gian t bo l ch cc phn ng sau y do cc
k h n g n g uyn kh c nhau gy ra c trn h by theo bng sau:
B n g 9.2: Thnh phn cc khng nguyn
v cc phn ng min dch do chng to ra
K h n g n g u yn

P h n ng m i n d c h

Vi khun, virus

Qu mn mun

Nm men, nguyn smh, ng vt,

S chng chu ca t bo do tip

k sinh trng.

thu c

Protein (+ t cht y )

Qu mn mun.

Hapten (+ protein ca bn thn)

Qu mn do tip xc, gy vim da.

Khng nguyn cy ghp

Thi b mnh ghp ngoi lai

Khng nguyn ung th

Thi b khi u

Khng nguyn m t bo

Gy ra mt s bnh t min

9.2.3.I. Dng qu mn do tip xc

Qu mn tip xc thng c gi l cc phn ng eczema gy
ra s vim da do tip xc vi cht gy d ng. Phn ng ny cng
c th do hapten nh cc kim loi nng (niken, crom) v rt

128

nhiu cht ha hc t nhin nh nha m cao su, sn t nhin,

nha tng hp, thuc nhum, mt s dc phm, mt s sn

phm ca thc vt nh p en tad exylcatech ol ca cy o ln
ht, cht c cy sn (Sum ac fau xvern is)...
Biu hin ca bnh qu mn l v tr tip xc vi mt hapten
s gy tch l y cc t bo bch cu n n h n bao q uan h cc tuyn
m hi, tuyn b nhn, nang lng v sau xm nhp vo biu
b. sau 48- 72 gi. Kim tra t bo hc cho thy r cc t bo n
nhn chim u th l CD4"^ v mt phn nh CD8^, cc t bo
Langerhans C D l'. Cc t bo T c hot ha ti ch bng cc
khng nguyn do cc t bo Langerhans trnh din s tit ra cc
lym phokin nh ILv. IL , GM-CSF. c bit l IFNy v IF N a . Hai
xitokin cui cng gy cm ng biu hin cc phn t kt dnh
gia cc t bo v cc phn t HLA-DR ca t bo ha sng
(keratinocyte). Tip theo cc t bo ha sng tit IL l, IL6,
GM-CSF cng hot ha lympho T. Cc t bo biu m (epithelial
cell) cng hot ha v gy di ng cc lympho T theo c ch gn
nh cc t bo ha sng.

9.2.3.2. Qu mn mun kiu tubecculn

Phn ng ny c khi ng bng mt s' lng rt nh lympho T C D 4\ T CD8" c hiu vi mt khng nguyn. Cc lymphokin ch yu tham gia vo phn ng qu mn l cc yu t
km hm s di ng ca i thc bo (MIF), TNFa, tip theo
IFNy to nn yu t hot ha i thc bo. Cc xitokin gy ra
ha hng ng IL8, NAP.l tc ng vo cc mono v tng s
biu hin ca cc phn t kt dnh ca cc lym pho. mono v biu
m.
D n g q u m n n y do s n h i m t r n g vi k h u n v v ir u s g y
ra (ln u tin c m t cho qu trnh nhim vi khun lao
{M ico b a cteriu m tu b ercu lo sis) nn c gi l qu mn kiu
tubecculin.
Biu hin cho qu mn l phn ng ban ti ch khi tim
di da cht tubecculin l mt cht gy nga, sn phm t phn
ca vi khun lao sau mt thi gian khong 48 gi. Tip vng
da dy cng ln. Du hiu c trng nht l s tch ly ca cc
lympho v cc mono c ngun gc mu v c chuyn thnh i
thc bo ca m. Khc vi qu mn do tip xc, dng qu mn
ny xy ra vng su di da. m khng phi lp biu b da.

129

9.2.3.S. Q u m n u h t

Qu mn to u ht xy ra do b nhim vi khun. c bit

trong bnh lao, ngi ta pht hin thy cc u ht trong cc vng
phi b tn thng.
Trong bnh phong, ngi ta thy c cc u ht c to ra t
cc t bo biu m, b nhiu t bo lympho xm nhp. Mt s'
bnh nhim k sinh trng sn mng (Schistosoma) cng c dng
qu mn mun to ra cc u ht.
9.2.4. Qu mn do kch thch (Kiu V)
Dng qu mn ny xy ra khi c mt dng khng th, chng
hn mt khng th c sinh ra do t bo tuyn gip b kch
thch cc bnh nhn Basedovv. Khng th ny c th gi l t
khng th (autoantibody) tc ng ln th th mng t bo tuyn
gip, kch thch t bo tuyn gip lm thay i cu hnh khng
gian th th ca hocmon TSH (Thyroid stimulating hormone) v
do gy bin i tng hp AMPv. Hon cnh cng tng t xy
ra vi cc lympho B khi c s kch thch ca mt khng th
to ra chng li cc Ig trn b mt t bo B.

130

Tm tt chng IX

1 . S p ng min dch qu mn kiu I biu hin c tnh phn

v ti ch hoc sc phn v ni chung do khng th IgE gy ra.

Cd ch ca phn ng l hnh thnh cu ni ca cc th th ca
IgE cc t bo mast to ra s bi tit ca cc ch^t ha gii
min dch cc t bo ngi.
2 . Cc dng biu hin chnh ca bnh l sc phn v, vim mi d
ng, kh th d ng, eczema d ng, mn nga ban tng
m, my ay, ph mch v cc d ng tiu ha.
3. S tng hm l ng IgE huyt thanh l mt du hiu khng c
nh v khng c hiu cho d ng nhng c th lin quan n
biu hin lm sng ca d ng.
4. Mt s cc yu t di truyn v mi trng (v d s nhim
kh quyn) c th gy ra bnh nhng ngi d cm nhn d
ng.
5. p ng qu mn kiu II v III u do cc khng th IgM v
IgG gy ra theo c ch hot ha b th, gii phng cc peptit
ca b th (C3a, C5a) v c gi l anaphylatoxin, gy phn
hy mng t bo v co c trn. Hng lot t bo tham gia hin
tng qu mn kiu II v III l tiu cu, bch cu a nhn
trung tnh, bch cu a axt, t bo mono v i thc bo.
6 . Min dch chng vi sinh vt l mt c ch tng hp qua trung
gian t ba v c ch tc ng phn t ca cc sn phm t
bo.
7. Min dch ung th nghin cu hin tng bt thng trong
sinh sn ca cc dng t bo min dch. Nguyn nhn di
truyn ca bnh l do s t bin ca cc gen gy ra hin
tng ri lon trong iu ho ca chu trnh t bo (ng ch
l gen p53 m ho cho protein p53 v gen p21 ras).
8 . Mi loi bnh ung th u do mt khng nguyn c hiu qui
nh. Ngi ta cng pht hin c mt s h cc gen ca
khng nguyn ung th. Vic hiu bit cc khng nguyn ung

131

th c th gip cho vic phng nga v chn on ung th c

bit l ung th c ngun gc virus.
9. Tham gia vo min dch chng ung th gm cc kiu t bo
nh NK, LAK, cc i thc bo, cc t bo a axt v.v...
10 .Hi chng tng sinh min dch l s ri lon v chc nng ca
cc t bo h thng min dch v to ra nhng sn phm c
bit l cc khng th n dng v cc protein c trng. Bnh
tng sinh min dch cng do nguyn nhn cc gen gy ung th
tc ng n chu trnh t bo c bit l s t bin ca cc
gen v cc nhim sc th.

133

Chng X. Min dch chng v i sinh v m in

dch ung th

10.1. Min dch chng vi sinh vt

Min doh chctng vi khun v chng nim s dng mt c
ch tng hp qua tru n g gian t b v c ch phn t, ngy cng

c pht Irin theo s lin ha ca cc loi, ng thi thch

ng di vi h sin h thi vi k h iiin v;' vt ch.

Trong s cc c ch ny. quan trng nht l s p ng min

dch t nhin tc l min dch khng dc hiu. l h thng b
Ih. cc thc bo, cc xitokin. y l s p ng tc thi nhm
bt gi v ph hy tc nhn gy bnh. Trong khi phn ng
vim , cng l s dp ng t nhin cho php tr n h c s la n

truyn ca vi sinh vt. Tnh min dch thch ng c hiu d s

dng tt c cc c ch min dch t nhin c hiu qu v s m in
dch thu c, c luyn tp trong i sng cho c th sin h
vt c th siig st. mt vi mt th gii dy ry vi sin h vt

v cc tc nhn c hi. Trons c dim min dch tip thu c

dc tnh ghi nh min dch cho |)h|) ching ta thc hin phng
l)hp tim chng phng bnh.
Ngi ta phn bit hai dng vi sitih vl xm nhp vo c th l
vi sinh vt pht trin ngoi bo v vi sinh vt pht trin ni bo.
Cc vi sinh vt ph;'it trin nfoi bo cl trn thot khi tc ng
ca b th v cc thc bo nhng l dch tc dng ca cc khng
th c hiu. Trong khi d cc vi sinh vL pht trin ni bo (vi
khun v k sinh trng) ch c th b |)h hy nh s hot ha
ca i thc bo. bng cc xitokin do lynipho T tit ra trong
trng hp p ng min dch dc hiu.

134

10.1.1. Cc c ch t nhin v thch ng oi tr vi sinh

vt nh lp da v tuyn nhy
Hng ro vt l v ha hc:
Da v tuyn nhy hoc nim mc l mt h sinh thi phc tp
m bo cho cc chc nng bo v ca c th nh; loi tr vi sinh
vt bnh l, chc nng thng tin th hin qua phn ng min
dch c hiu vi cc vi khun xm nhp, chc nng bo v bng c
ch hoi sinh.
- Lysozym ca bo quan t bo v mt s cht tit c kh nng
dit vi khun xm nhp.
Vai tr min dch ti ch ng rut ch yu l bo v c
th chng li c t vi khun nh trong bnh a chy v bnh t
(cholera)

10.1.2.Phn ng vim ti ch v h thng chng li nhm

trng
Ngay khi vi khun vt qua lp ro bo v (da v tuyn nhy),
chng s khi ng bng cc phn ng vim. Ba yu t' quan
trng lin hip c hiu qu chng li nhim khun l: b th, cc
xitokin v cc t bo thc bo. Chc nng bo v chng li nhim
khun ca b th c chng minh l C5, C6 , C7, C8 hoc
propecdin trong trng hp nhim cu trng Neisseria meningitidis v N. gonorrhoea. Cc xitokin nh TNFa, IL la v IL ip
IL 6 , IL 8 , IFN cng gy kch thch cc phn ng vim ti ch v
h thng. Mt s protein c bit l protein phn ng c (CRP)
cng tham gia phn ng vim.

10.1.3. p ng min dch c hiu chng nhim khun

p ng min dch c hiu chng nhim khun c th hin
cc c ch ch yu sau;
10.1.3.1. Sn xut cc khng thchng lai cc polixacarit
l cc eptop ca cc t bo vi khun v 'nm

S p ng ca cc t bo B thng l vi dng (oligoclonal)

ngha l c mt vi dng sinh ra cc IgM, IgG i khi c c IgA^
ngi. S pht trin mt kho d tr t bo B chng li cc poly -

135
x a c a r it c a vi k lm n Streptococcus p n e u m o n ia e ngi c c
liem x u t h i n m un, kling trc 2 hoc 3 tui.

10.1.3.2. p ng ca cc lym pho T

(' c lym j)ho Taf5 n li n bil cc p e p tit t p ro te in c a vi k h u n
'lo cc A P C (c l(') II hoc l) 1 c a M H C) t r n h d in. T h n g
ihon. cc pi-<)toin tit hoc l s;in p h m th o i h a c a vi sin h
vt (u dc t r n h din clio cc ly m p h o TCD4*. N goi ra, ngi
l a cn tm thV cc tiu (|un ih lymphoTCD8'^a[3 x u t h in , c
h iu \i cc k li n g ngviN n ic kt hp vi cc p h n t lp I c a
M H C. (' c k h n g n g u y n ca vi k h u n c t h c t o r a th e o c
('h n l b n g cch cun m n g sin h c h t (Coiling p hago cyto sis)
c a l b o t h r bo. sa u c h hin i h n h p e p ti t v k t hp vi
irotoin l|) I c a HLA. l tr n g hp c a B o rre lia b u rg odo rIVri d (lc m t.

10.1.3.3. Cc c ch hiu qu s dung xitokin

C c ly m p h o T gy h i u q u chng n h i m k h u n p h t t r i n b n
ngoi h o c b n tro n g t bo b n g n h n g tn h i u h a hc, c
l)it l cc x ito k in . B n th n -cc x ito k in li c t h g y c m n g
v k h u y c r h (li s s n x u t xitokin c a cc i th c b o v c a
c t t b o N K . Bn c n h , cc k h n g t h c t h c n h ln b
m t 'v i k h u n , hot ha b th v lo iu k i n o p so n in h a v
hiii t n g Lhc bo. Cc x itokin I L l, IL6, T N F a , IFN y l m t n g
t n h c h n g c h u c a v t ch. lFN y lun c s n x u t t i n h i m
( r n g t cc t b o NK. lip theo l t ly m p h o Typ v ly m p h o
'Pap.
Ngoi ra , ngi ta cn th y c cc pi-otein sc n h i t (hsp: h e a t
sh o c k p r o te in ) c n g phi hp tc d n g vi cc t b o T c h i u
VI c h n g t r o n g vic bo v ch ng li cc vi s in h v t k h c n h a u .
P r o t e in sc n h i t c k h n n g kch th c h c h n lc cc t bo Ty
v r t c t h q u n th Ty c chc n n g loi b cc t b o b t
t hi ng (t bo b n h i m k h u n hoc cc t b o u n g th).

Co siu khng nguyn (superantigene) nh c nh

iTgha l cc phn t c kh nng lin kt vi cc phn t lp II
(.'a MHC v vi cc trnh t peptit ca mt s h TCR (Vp), c
tc dng hOct ha nhiu dng t bo T v kch thch vic gii
pling cc lymphokin L 2 , IFNy v TNFa. Cc du hiu nhim

136

c siu khng nguyn t cu khun Staphylococus c

quan st thy l st, a chy, ph mch no, ph mch phi v
thn, do nhim c thc phm.

10.2. Min dch ung th

10^.1. Khi nim ung th, cc gen ung th v km hm ung th

Ung th (Cencer, tumour) l mt bnh ca cc c th a bo.
trong cc t bo phn chia bt thng v khng c iu
ha, dn n s bit ha khng bnh thng (cn gi l neoplasia).
Ung th xut hin ni chung l do s tch ly li cc t bin
ch yu cc ng vt c xng sng bc cao. Ung th cng ng
ngha vi s hnh thnh cc khi u (tumour) c nghin cu
kh chi tit cc loi ng vt c vit l ngi, nhng cc
khi u cng xut hin thc vt (v d bnh khi u bt thng
ca cy do vi khun Agrobacterium tumefaciens gy ra, bnh
"Crown gall").
Ba c im ca t bo ung th l:
1 . Tnh bt t trong sinh trng ngha l t bo phn chia v hn
v khng bit ha.
2. T bo b bin dng khng tun theo s kim sot ca cc yu
t sinh trng.
3. T bo bin dng c kh nng di c (metastasis) ngha l di
cn xm nhp vo cc m t bo bnh thng khc v pht
trin thnh mt qun th t bo ung th mi, to khi u.
Bnh thng t bo khng bin dng ung th c cc gen c

gi l gen tin ung th (proto-oncogene) thc hin cc chc nn

bnh thng l to ra cc sn phm iu ho 8 sinh trng v
bit ha t bo. Nu t bo b nhim virus mang gen gy ung th
(oncogene), cc gen tin ung th ny b t bin tr thnh cc
gen gy ung th (oncogen) c hot ng qu mc v khng bnh
thng. Cc proto-oncogene ny cng c th b t bin do nhiu
tc ng mi trng nh phng x, ha cht.
S tng sinh khi u c bn cht n dng, nhng cc t bo
mi sn sinh t mt dng li rt a dng v kiu gen (genotype)

137

biu hin qu mc mt s gen, mt i mt s nhim sc th... v

a dng v kiu hnh. S bt thng v di truyn t cc t bo
ung th do tip thu c dn n c tnh tng trng v
hn. lm ngng bit ha. lm mt kh nng km hm tip xc v
tng kh nng di cn cc t bo ung th bt thng n khu tr
nhng m t bo c bit no y.
Cc sn phm ca cc gen tin ung th t bo bnh thng
kim sot cc tn hiu hot ha v sinh sn t bo. l cc th
th ca cc yu t tng trng, cc protein truyn tn hiu ho
hc (chng hn: serin treoninkinaz, protein G...), cc protein
tham gia bo v chng oxit ha Bcl-2 hoc cc yu t dch m (Cmyc). Cc gen tin ung th c th c hot ha do t bin. S
dt bin gen ras c thy nhiu cc khi u ca ngi lm
km hm cu hnh khng gian hot ng ca protein p2 1 ras lm
hot ha t bo. Tc ng ca gen ung th gy ra s chuyn
on nhim sc th (nhim sc th 14 v 18), gy ra s biu hin
qu mc ca Bcl-2 (protein anti-oxydant) lm mt i hin tng
cht theo chng trnh (apotosis) ca lympho B trung tm
ngun.
Trong khi , cc gen km hm ung th (anti-oncogene) hoc
(tumor suppressor) c pht hin khi phn tch cc t bin
ca cc dng ung th. Cc gen ny m ha cho cc protein ca
khung t bo, hocc protein iu ha chu trnh t bo, hoc sa
cha ADN. ng ch l gen p53 m ha cho protein p53 b
nh ch hot ng trn 50% cc khi u ca ngi. Protein p53
rt t biu hin cc t bo b sc (stress), b thay i cu trc
ADN. T khng gip cho vic sa cha ADN trc khi phn
chia t bo. S t bin gen p53 dn n tch ly mt dng protoin bt hot, lm mt kh nng sa cha ADN v cho php t
bo b bin dng c tnh sng st. Nh vy, gen km hm ung
th c vai tr km hm sinh tr n g t bo v sn phm ,ca
gen ny l nhng cht iu ha sinh trng t bo.

10.2.2. p ng min dch c hiu chng ung th

10.2.2.1. K h n g nguyn ung th

Ngi ta pht hin ra cc khng nguyn c hiu ca cc

kh(M u ca ngi. Tip theo ngi ta cng nhn thy cc phn

138

ng hn hp gia cc lympho T vi cc khng nguyn ca khi u

cng c nhn thy. Trong cc trng hp ung th, cc
lympho T c sinh sn ch yu l dng lympho T CD4* v mt
phn l cc lympho T CDS"^ c hiu vi cc t bo ung th tit
ra TNFa. Boon v c c c n g s (1 9 9 4 ) p h t h i n c m t hi
cc gen ca khng nguyn ung th melanoma v gi l MAGE
(melanoma associated genes). T mu ca bnh nhn mang bnh
melanoma MZ2 , h tch c cc lympho T CD8 * c hiu vi
khi u MZ2 -E.
Cu trc peptit ti u c sn xut t gen MAGE-1 >c
xc nh t dng t bo MZ2 -E bao gm 9 axit amin (nonapeptitt)
l mt epitop T lin kt vi HLA-Al. Cc khng nguyn ung th
khc cng c xc nhn, chng hn cc t bo ung th dnig
B bc l khng nguyn CD19 v CD2 0 , dng T bc l CD25.
10.2.2.2.Kh u do vru s g y ra

Rt nhiu khi u thc nghim v mt s kh u ca ngi dlo

virus ung th gy ra. dng virus ARN v ADN, v d virus Epstein-Barr (EB.V) c kh nng gy ung th vm hng. Cc viruis
13 gy vim gan (HBV), virus c (HCV) cng c kh nng gy umg
th gan. Ung th c t cung do mt s" dng papilloma virus c.a
ngi (HPV 16 v 18). Cc retrovirus HTLV -1 thng tham giia
vo ung th bch cu T (leukemia) ngi trng thnh. Tn Si
ca ung th tng rt cao cc bnh nhn thiu ht min dc;h
(i vi ngi ghp m, b bnh AIDS), rt c th do c ch gii
km hm min dch, (Nossal,1993).

10.2.3.Min dch t nhin chng ung th

Tham gia vo min dch t nhin chng ung th gm ba kiU

t bo;
- Cc t bo NK: Cc t bo ny c kh nng phn hy in itro
cc dng ung th biu hin yu hoc khng biu hin cc ph.n
t MHC. S tng tc c hiu phn t cho php phn nig
gy c cho t bo ung th cn cha sng t. Cc t bo LAKv,
t bo dit c hot ho bng lymphokin (Lymphokin act)ivated killer Cell) nhn c nh nui cy lympho khi c mit
IL 2 c kh nng phn hy in vitro cc t bo bt ngun t m)t
khi u.

139

- Cc i thc bo: Chng c hot ha in vitro nh cc xitokin

nh IFNy v cc sn phm c ngun gc t vi khun v c kh
nng phn hy in vitro cc t bo ung th. Tnh c hiu
tng tc phn t trong phn ng gy c i vi cc t bo
ung th cng cha c bit r. TNFa c sn xut ra t cc
i thc bo hot ha c kh nng ph hy nhiu dng t bo
ung th.
- Cc t bo a axt: c hot ha bng IL5 v cc cht ha gii
khc c tnh c cao i vi cc m t bo bnh thng v
vi k sinh trng sng trong cc t bo khi u.

10.2.4. Liu php min dch v min dch phng tr ung th

Vic nhn bit cc khng nguyn ung th c hiu l mt kh
khn nn a s cc bin php min dch cha bnh mi ch da
vo s kch thch khng c hiu cc phn ng min dch. Tuy
nhin ngi ta cng s dng cc phn ng min dch c hiu
khng nguyn cho vic d phng cc khi u c ngun gc virus.
V d cc vacxin chng virus vim gan B, v ang c m rng
cho cc vacxin FBV, HCV, HPV-16... Cc liu php th nghim
tim chng vacxin vi ung th melanoma ang c tin hnh
vi cc peptit khng nguyn ung th; Th nghim trn c p
dng cho cc bnh nhn kiu hnh HLA-Al. Cng c th thc
hin bin php gy min dch bng cc peptit MAGE-1 vi s c
mt ca t cht hoc bng cc vect biu hin trnh t m ha cho
khng nguyn ny (v d retro virus, BCG...)
Ngi ta cng c nh s dng khng th n dng chng li
khng nguyn ca mt s bnh ung th. Cc khng th ny c
th c ci bin bng cch gn vi mt ng v phng x hoc
mt loi thuc, c t vi khun hoc c t" thc vt nhm tiu dit
cc t bo ung th.
Cc xitokin, IFNa cng ang c s dng cho nhng kt qu
kh quan trong vic phng tr mt s bnh ung th. Ngoi ra,
ngi ta cng s dng c nhng t bo LAK ca ngi bnh c
nui cy khi c mt IL 2 , sau tim tr li cho ngi bnh.
Mt nguyn tc cha bnh ung th khc ang c nh gi l
s dng mt s dng phn t nh cc dn xut ca vitamin A
(axit retinoic) hoc mt s' khng th cho php gy ra s bit ha

140

sm cc t bo ung th v t to ra qu trnh sinh l ph hy

cc t bo ung th bng c ch apoptosis.
Cc liu php ha hc v phng x, kt hp vi vic xy dng
li h thVig to mu bng cch cy ghp cc t bo ngun
(0034"^, ThyT) ca bn thn bnh nhn (ghp cng ngun:
autogreff) cng c p dng.
Mt bin php khng phi l lin php min dch l nu c th
ct b cng sm cng tt khi u dng cha di cn (ung th v)
khi pht hin sm bnh l ko di thi gian sng.

10.3 Hi chng tng sinh min dch v cc bnh ung th

10.5.1.Khi nim
Hi chng tng sinh min dch l nhng bnh tng cng qu
trnh sinh sn ca t bo dng lympho (t bo T v B). Nghin
cu hi chng ny lm tng thm s hiu bit v h min dch,
cho php phn tch v chn on s lan truyn dng t bo n
dng, cc qun th v cc phn t xut hin mt s" lng rt t
trong c th bnh thng. Vic nghin cu cu trc cc phn t
Ig trong cc bnh tng sinh min dch cho php hiu bit cc Ig
n dng trong bnh l trc khi pht minh ra phng php sn
xut cc khng th n dng ng dng cho y hc.
Nghin cu hi chng tng sinh min dch gip cho vic phn
loi chnh xc hn cc bnh l v t bo hc v di truyn t bo,
tm hiu c m quan h gia hi chng bnh ny vi cc loi
virus(E-BV, HTLV-1...).

10.3.2.Tinh n dng ca bnh tng sinh min dch lympho

Trong a s trng hp ung th, sinh sn t bo mang tnh
n dng. iu ny c chng minh nh mt dng t bo ca
bnh ch tit ra mt loi khng th n dng c cu trc giVig
nhau.

141

10.3.2.1.Cc kh n g th n dng ca huyt th an h

Cc khng th dn dng c cu trc ging nhau, tch din nh

nhau v to ra mt bng protein r nt trong in di. Cc k
thut in di phn giii cao (lp mng agaroz) cho php phi hin
cc Ig dn d n g k h n g t h y c i n di ti u c h u n ( h n h 10.1).

K thut phn tch in di min dch l cn thit, cho php xc

nhn thuc tnh ca ch mt chui L, chui Kappa hoc lambda
v cc izotip chnh xc (IgAl, IgA2 , IgGl, IgG2 ...) ca mt chui
nng H trong cc bnh u ty (myeloma).

;;; ini 5^-196

arthl;
s*t\

s?

Ulpi
U5ul

f,r?.

Upl
lriA
4 ^ 1 -#

H n h 10.1 nh in di min dch cho bit cc cung kt ta (c du sao)

ca huyt th a n h bnh l (SP) khc bit vi cung kt ta bnh thng
(SN) khi s dng cc khng th khng chui nng v khng chui nh
khc nhau, y trnh by hai dng bnli l khc nhau (a^ v bO

142

'

H n h 10,2. nh in di huyt th a n h trn gel

tm polyamid xc nh cc trng hp bnh u
tu dng IgG, IgA, IgM, cc chui nh X v K.

1. Huyt thanh bnh thng.

2.

I g G X.

3.
4.
,
6.
7.
8.

IgG X (u tu).
IgA K (tng sinh macroglobulin).
IgA K (hai vch kp ca bnh u tu).
IgM K (Bnh ung th \Valdenstrom).
IgM K (Bnh ung th Waldenstrom).
IgG X ca nc tiu bnh u tu ch thy r bng protein Bence Joniis
type K.
9. Ba dng bt thng ca cc Ig mi tn ch IgM K, IgGi v IgG X (ung
th bch cu: leukemia).

10.3.2.2. Cc hu qu sin h l bnh

Cc Ig n dng ca huyt thanh c th gy ra s ri lon

bnh l do nng qu cao trong huyt thanh, do tnh c hiu
v cu trc bt thng ca chng. Cc khng th n dng c th
lm tng tc lng ca hng cu, lm tng hm lng protein
ca mu v to thnh cc cun bng hng cu. Mt s hi chng
tng sinh gy ra cc hu qu ng ch sau;
- Hi chng tng nht ca mu do cc IgM v IgG n dng,
gy tn thng tim mch v tn thng y mt. Cc khng
th dn dng c th lin kt vi cc th th Fc ca tiu cu gy
ra bin chng chy mu v nhim trng.
- Hi chng tn thng t bo v m t bo do s lng cn ca
cc chui nh ca Ig n dng, xy ra bnh ng thn do u
ty. S tn thng cc ng dn trong thn do tch t qu ln
cc protein Bence Jones (PBJ) l dng dime ca chui nh
khng th n dng dng t do.

143

- Cc bnh "Amylose" ng "cn tinh bt" do s tch ly mt s

dng protein (chui nng v chui nh ca Ig) v cc t bo
plasma n dng gy ra tn thng ti ch thnh mch mu,
li, tim v c xng, ng tiu ha v phi.
- Cc bnh ng cn chui nh v Ig n dng d thn, hg tiu
cu thn, gan, tim v i khi cc m t bo khc. S ng
cn ny c pht hin bng cc khng th khng kappa hoc
khng lambda.
10.3.2.3. Mt s v du tng sinh n dng ca t bo B

10.3.2.3.1 Bnh u tu nhiu ch (multiple myeloma)

u ty nhiu ch hay a u ty l s tng sinh c tnh dng t
bo lympho B, kiu hnh t bo plasma. Bnh ny dn n tn
thng xng, rng xng lan trn hoc ti ch, i khi gy
xng. Phn tch biu u ty v sinh thit xng cho thy r s
xm nhp cc t bo plasma c hnh thi khc nhau, gy ra bnh
suy ty km theo thiu mu.
C hai triu chng bin chng ca bnh a u ty l: tn
thng thn, tn thng ng dn ca thn v tiu cu thn, ng
cn trng amyloz, gim tng hp cc Ig bnh thng lin quan
n d ha qu mc (hypercatabolism) trong cc bnh u ty ca
IgG. Bin chng tip theo l nhim trng. Biu hin ca bnh l
au n ti ch v lan truyn.
V nhng c im ha sinh min dch, ngi ta phn bit
4 dng u ty khc nhau l:
- Khng th n dng ton b, cha trong huyt thanh ch yu,
c t hoc khng c trong nc tiu.
- Khng th n dng +PBJ xut hin trong huyt thanh
nhng ch yu l PBJ, trong nc tiu n dng chi c Ig n
dng v khng c PBJ (PB.J l protein Bence Jones).
- C PBJ, c hoc khng c Ig n dng trong huyt thanh.
Trong nc tiu c Ig n dng.
- u ty "khng bi xut" Ig n dng v PBJ.
10.3.2.3.2. Ung th bch cu (eukemia) hay bnh mu trng
Bnh mn tnh c u th nam gii c tui trn 50. Khi bnh
chuyn sang dng c tnh ca nguyn bo lympho B v nguyn
bo lympho T c tin lng xu th bnh nhn s biu hin r
khng nguyn chung cho bnh bch cu nguyn bo lympho. C

144

th dng khng th n dng c hiu khng li khng nguyn

ny (khng th J5) cho xt nghim ELISA pht hin bnh.
c im ca bnh l tng sinh n dng t bo B c mt
thp IgM v IgD trn mng t bo. Ung th bch cu dng mn
tnh (chronic lymphoid leukemia-CLL) him thy d la tui di
50 v thng tr nn lnh tnh, nhng cui cng cng c 20%
bnh nhn th hin khng th n dng trong huyt thanh s c
tin lng xu, tr thnh c tnh.
Hai dng bin chng ch yu ca bnh CLL l s thiu ht
min dch th cp km theo vic gim st sn xut khng th v
pht sinh cc bnh t min, c bit l bnh tan hng cu t
min (hemolytic autoimmune disease)
10.3.2.3.3. u lympho hay lymphoma
Ngi ta phn bit hai dng lymphoma: dng u lympho khcn
phi Hodgkin v bnh lympho-Hodgkin. u lympho khng Ho4gkin l dng biu hin ch yu do t bo B to ra mt kiu Ig c
ch mt dng chui nh (kappa hoc lambda) Tri li trong tn
sinh dng B phn trn, ngi ta thy r biu hin ng thi c
hai dng chui nh l K v X. Bnh nhn b lymphoma Hodglin
c c im l kin trc ca c quan lympho b ph hy v xut
hin cc t bo khng l, cha hai nhn gi l t bo RedSternberg.
Bnh ngng kt hng cu lnh l do tng sinh bch cu ly
xng, tit ra mt Ig n dng huyt thanh, c hot tnh t
khng th (autoantibody) chng li hng cu ca bn thn.
Lymphoma Burkitt (BL) hu nh lin quan vi virus EpsttinBarr, biu hin hm v phn bng.
10.3.2.3.4. Bnh macroglobulin Waldenstrom
c im ca bnh l tng sinh dng t bo B vi nhiu kii
hnh t t bo B hnh dng nh cho n cc t bo plasma (nhiu
dng trung gian ca B). IL 6 ng vai tr quan trng trong vic
duy tr dai dng s chn ca dng B v s tng sinh dng B n
ra ty xng, hch bch huyt v c l lch. Xt nghim lia
sinh min dch cho thy xut hin mt lng ln macroglobi.lin
c khi lng 400.000 dalton bao gm cc IgM n dng v x-2
macroglobulin trong huyt thanh ngi bnh. Hi chng a
bnh l tng nht ca mu, mu mu nht v c bin chng
thiu mu do tan hng cu v chy mu xut huyt.

145

10.3.2.4. S t n g sinh dng lym pho T

S tng sinh bch cu c tnh dng lympho T hay bnh mu

trng dng T (T.Cell leukemia) xy ra ngi trng thnh c
bit c nhiu Nht Bn v Trung M. Bnh do loi retroviru
HTLV-1 (Human T.Cell leukemia virusl) gy ra. u lympho T r't
thng xuyn nm v tr biu b c to thnh t cc lympho
T CD4^, T CD8 * bit ha. Cc lympho T ny khi tip xc vi
biu b s gii phng ra cc lymphokin (GM-CSP; IFNy, TNFa).
Biu hin bnh l l do tc ng ti ch ca cc xitokin ln biu
b v lp da trong hay chn b (derma).
10.3.2.5. Nguyn nhn di truyn v nguyn n hn t bo
ca bnh.

Rt nhiu khi u ca cc lympho B pht sinh km theo s mt

kh nng iu ha ca mt tin gen gy ung th (protooncogene) C-myc hay cn gi l gen tim n lin quan n ung
th. Gen C-myc c vai tr nht nh trong vic chuyn trng thi
Go/Gi ca chu trnh t bo lympho v c th i vi nhiu dng t
bo khc. S tng cng biu hin ca gen ny s bo trc s
hot ha lympho.
Ngi ta nhn thy s iu ha biu hin qua gen C-myc b v
phm s lm cn tr t bo tr li trng thi ngh Go trong chu
trnh t bo v bt buc t bo sinh sn lin tc. S ri lon tng
sinh t bo B thng km theo hin tng chuyn on ca locus
C-myc trong cc nhim sc th. c bit l trng hp u lymphoma Burkitt, ngi ta lun lun thy c s chuyn on ca
oncogen C-myc vi cc trnh t iu ha locus IgH (t4;18 c
75% cc trng hp) hoc cc locus IgK hoc IgL (t2;8 hoc t8;22
c ti 25% trng hp). Gen C-myc l gen "pht trin sm" c
chc nng hot ha t bo biu hin qu mc cc t bo khi
u t di s kim sot ca cc yu t phin m cc Ig. C th
minh ha c th s chuyn on gia cc nhim sc th 8 v 14,
trong c cha gen C-myc locus ca chui nng o. gy ra bnh
lymphoma Burkitt (Hnh 10.3).

146

Nhim sc th K

Nhim sc th 14

Nhim sc th X

Nhim sc th 14

t bin
chuvn
on

VH
H in h 10.3. S chuyn on ca gen C-myc locus ca chui
nng trong bnh lymphoma Burkitt. (theo I. Roitt. 1990.)

Sau y l tng kt mt s v d v s chuyn on ca cc

nhim sc th trong cc hi chng tng sinh min dch.
B n g 10.1. S chuyn on cc nhim sc th gy ra bnh tng sinh
min dch (theo Kaplan v Delpech - Biologie molculaire et Mdicine,
trang 479 - Paris 1993)

Nhm
sc
the

Kiu ung
th

Chuyn don

Gen
th
2

Nhim
sc
th

Lympho H
Lym pho B

t(8:14)(q24;q32)

IgH

14

C-myc

t(2;8)(qll;q24)

IgK

C-myc

I(8;22)(q24;qll)

JgL

22

bC * 1

11

t(ll;14)(ql3:q;2)

li?H

14

bCl - 2

18

t(14;18)(q.32;q21)

IgH

14

Pbx - 1

t(l;19)(q23;ql3)

R2A

19

IL -

Ivyinphoma
Burkitt
Lymphoma
Bkitt
Lympho ma
Burkitl
Loukomia
lymphoma
Ly mpho ma
nang
Leukemia
lymphoina
IxHikcmia
lymphoma

K5;14)(q31;q32)

IgH

14

t(ll;14)(ql3:q32)

TRCD

14

t(7;19)(q34;q34)

TRC*B

1(7:11)(q.35:q 13)

TRCB

Gen th
nht

tipho T

tal - 1

Tan ' 1

THC-

11

U'ukemia
lymphoma
Ixukcmia
nguyn
bo
Ix^ukemH

147

c jnyc

Hox - 11

10

ly m pho ma
K<ukoniia
ly rn pho ma
I>oukomia

t{8;14)(q24;qll)

TRC-A

14

t(ll:14)(q25;qn)

TRC-D

14

t(ll;14)(ql3;qll)

TRC-I)

inv(14)(qll:q32)

IgH

lynihorna

rbtn - 1

11

I.oukemia
ly)i)hom a

rCRA

Loukcmia
ly m p h o m a

10.3.2.6. Bnh t n g sinh m in dch lin quan n chui

n ng

Cc bnh ny c c im l huyt thanh ca bnh nhn c

mt loi Ig n dng nhng khng c cc chui nh (dng Ig c
cu trc b't thng). Bnh th hin ba lp Ig ch yu l IgM,
IgG v IgA (c bit l IgA|). Trong huyt thanh ngi bnh, cc
phn t Ig c chui nng b ng ha r t cao, ng ha l kt hp

vi nhiu loi gc ng. l c im quan trng v s bin

i cu trc ca cc chui nng Ig. Bnh ca chui nng y thng
din bin di dng tng sinh min dch v biu hin ca bnh
t min. Trong khi bnh ca chui nng a th hin s tng
sinh dng nguyn bo lympho IgA), xm nhp vo rut non v
cc hch mng treo rut, lm teo nhung mao rut, dn n hu
qu suy dinh dng do hp th dinh dng km.

10,4. Mt s" c im lm sng ca ung th

10.4.1. Ch th ung th (Tumour m arker)
T lu cc nh khoa hc sinh hc v y hc mong mun tm ra
cc ch th ung th pht hin cng sm cng tt s chuyn
dng c tn h ca t bo ung th. C mt s" hp ch t ho sin h
c pht hin c quan h cht ch v i khi c tnh c hiu
ct'i vi mt s' bnh ung th xem nh l nhng ch th ung th.
Ch th ung th c nh ngha l nhng i phn t khi xut
hin mt bnh ung th, c nng thay i theo chiu hng
tng ln lin quan s pht sinh v tng trng ca nhng khi u
c tnh mt bnh nhn.
Ch th ung th c th chia lm hai dng; ch th t bo v ch
thi th dich.

148

- Ch th ung th dng t bo bao gm cc khng nguyn trn 1)0

mt cc t bo, cc th th hormon v th th yu t tn.
Lrng, nhng bin i di truyn (bin i gen) ca t bo.
- Ch th ung th dng th ch bao gm cc cht ho sinh c
pht hin nhng nng qu mc bnh thng c mt trong
huyt thanh, nc tiu v cc th dch ca c th.
Chng c cc t bo hoc m ung th tng hp v tit ra, t
khi u b ph v hoc c to ra t cc phn ng ca c th
i vi khi u.

10.4.2 Phn loi ch th ung th theo kh nng c hiu

bnh.
- c hiu cao khi ch th ung th khng c pht hin i
tng kho v u lnh tnh.
- C nhy cao l d pht hin giai on sm khi ch c mt
t bo ung th xi hin.
- c hiu c quan ngha l ch xut hin mt c quan b uri

th.
- Xut hin tng quan vi giai on ung th v kch thc kh u
- Tng quan vi tin lng v thi gian sng.
- C gi tr d bo.

10.4.3 Mt s ch th ung th lin quan vi bnh

1.CEA l mt glycoproteinlSO kDa cha 60% ng (carbohydrate) l mt trong nhng khng nguyn ung th thai, thng
xut hin nng d cao trong huyt thanh bnh nhn ung
th trc trng, v mt s bnh ung th ng tiu ho (bnh
thng, ngi kho khng ht thuc l, nng CAE < 3-5
ng/ml) ngi ht thuc tng t 3-10 ng n 20 ng/ml. CAE
c sn xut trong s pht trin phi v thai. Sau khi sinh,
CAE ngng sn xut nn ngi trng thnh c nng rt
nh.
Ngi ta tm ra c t nh't 14-16 gen thuc h gen CEA m
ho cho CEA, v cc cht tng t CEA hoc cc protein lin
quaii n qu trnh mang thai (BGP).
2.
AFP (Alpha Petoprotein) l mt glycoprotein 70 kDa cha
khong 2.5% ng, c tng hp gan v ti non honf

149

ca thai v c tip vo huyt thanh tun th 13 ca thai

k. Sau khi sinh, nng AFP trong huyt thanh tr s sinh
gim dn v ngi trng thnh, kho mnh ch cn 3-5
ng/ml. 90% bnh nhn ung th biu m gan tin pht c nng
AFP tng ln hn 1000 ng/ml, i khi t 10.000 n
1 .000.000 ng/ml (Abedev, 1971 Saito, et al 1990, Taketa, et
al. 1990).
iu ng lu l AFP thai k c mc glycozyl khc
vi AFP ca ung th gan v mt s dng AFP bnh l khc.
Taketa v cng s (1990), ch ti c im ny v s
dng lectin nhn bit c hiu AFP glycozyl bnh l
pht hin v phn bit bnh ung th vi cc AFP bnh
thng thng khc.
']. HCG (Human Chrionic Gonandotrophin) l mt asialo glycoprotein (glycoprotein khng cha axit sialic) c khi lng
phn t 46 kDa, bao gm hai tiu n v a v p lin kt khng
cng ho tr vi nhau. Tiu n v p ca HCG c hot tnh c
liiu ring cho HCG, trong khi tiu n v a gihg hocmon LH
(hocmon th vng: Luteinising hormone). 0 giai on u ca
thai k, HCG c t bo l nui phi (Trophoblaste) v nhau
ihai tng hp. HCG c chn on c thai (pht hin c hiu
s c mt tiu n v p. Tuy nhin, khi nng chui p t do
tiig cao trong trng hp ung th bung trng hoc tinh
lion. Cc xt nghim chi dnh ring cho tiu n v p t do
cho nhy 100 % i vi ung th t bo nui thai v nhy
70% i vi ung th tinh h o n khng ht. Trong bnh ung th
nhau

thai lun lun xut hin HCG, v khng xut hin AFP;

nhng bnh ung th ti non hong th ngc li: AFP

dng tnh v HCG m tnh. Nng HCG c th tng ln
trn 1 triu lU/ml bnh ung th t bo nui dng nang sn
(40 -50% ung th biu m thai dng nang sn). Nng
HCG tdng ng vi giai on pht trin khi u v tin lng
bnh ung th t bo nui v t bo mm. Ngi kho bnh
thng c nng HCG di mc 5 lU/ml.
4. CA 15 - 3 l khng nguyn ung th c t bo ung th v
mt s" t bo biu m tit vo mu v dch c th. CA 1 5 - 3
c pht hin nh hai khng th n dng l 115 - D8 v
DF3. CAI5-3 c dng pht hin theo di, iu tr v pht

150

hin s di cn trong ung th v. 70% bnh nhn n ung th

v b di cn u c nng CA 15-3 tng. Gi tr nng
CA15 -3 tng ln cng xut hin trong ung th bung trng,
ung th tu, rut kt v ph qun. Tuy nhin nng cao cn g
thy bnh s gan, vim gan v mt s bnh phi, bnh v
lnh tnhi.
5. NSE (Enolaza c hiu ndron thn kinh; Neuron - Specifiic
Enolase) l mt isozym ca enolaza bao gm hai polypeptid
gn nh ging nhau, mi chui 39 kDa. Trong qu trnh n-g
phn(glycolysis).
NSE xc tc cho s bin i 2-photphoglycerat thnh phoitphoenolpyruvat v tham gia vo sinh tng hp hexoza. NSE c n
ion
v
nh l nhng coactor v b km hm bng
phosphofluoride.
V NSE nh khu mc t bo nn vic pht hin thy n
trong huyt thanh ch ra hin tng hoi t t bo ung th. D'o
, NSE l mt ch th khng thch hp lm cho vic pht hi n
giai on sm ca ung th. Cng c th s dng ch th NSE
phn loi m hc. Ung th t bo nh ca biu m ph qun phit
hin rt nhanh, c th c x l ho tr liu. Vic phn loi mi
b bnh da vo NSE c th to iu kin d dng cho cch l.a
chn phng php cha tr. Tuy nhin, cn phi hp vi vic xic
rih ch th CEA. Khi nng NSE tng cao qu l l , 8 ng/ml Si
cho tin lng xu, nhng nu nh hn l l , 8 ng/ml, thi gian snig
lu di hn.
Ch , v NSE c tm thy trong t bo plasma, tiu cu
nn ngi b bnh tan huyt, nng NSE cng cao.
Cng c th thy NSE tng ln c ngha nu mu ly ra
qu 60 pht trc khi ly tm tch huyt thanh.
6 . PSA (Khng nguyn c hiu tuyn tin lit: Prostate - Sptecific antigen) l mt glycoprotein 34 kDa c hnh thnh mi

tuyn tin lit c mt c trng thi bnh c tnh v ln h

tnh. V vy PSA khng thc s l ch th c hiu ung th c:
quan. Tuy nhin PSA cng ng gp cho vic d bo v bmh
ca tuyn tin lit giai on khi pht sng lc cc ri ro
i tng nam gii trn 50 tui.
V chc nng sinh hc, PSA l mt proteaza serin gip chio
qu trnh lm lng tinh dch bng c ch ct fbronectin ca tinlh

151

dch, bnh nhn ph i tuyn tin lit lnh tnh(benign hyperplasia), nng PSA cng tng trong huyt thanh v c
)ht hin nhy hn so vi PAP(Prostatic acid phosphatase).
S sn xut PSA c th b c ch bng cch iu tr vi anti androgen.
7. PAP (Photphataza axit ca tuyn tin lit: Prostatic Acid
Phosphatase) l mt glycoprotein 100 kDa c sn xut t lysosome ca t bo biu m(epithelian cell), photphataza axit
bao gm 5 isozym c mt nhiu loi t bo v dch c th
khc nhau nh: tiu cu, hng cu, h thng li ni m (gan,
lch), tu xng v t bo m tuyn tin lit. Tuy nhin
tuyn tin lit. isozym bng 2 c trng cho m c gi l
PAP nhng khng c hiu cho ung th v nng ca n cn
tng ln bnh ph i tuyn tin lit lnh tnh. Ch th PAP
cng c dng xc nh v theo di iu tr bnh ung th
biu m tuyn tin lit (Prostate Carcinoma). Nng PAP
tng ln huyt thanh ch r s tin trin ca bnh ung th.
Trong khi ngi kho bnh thng nng PAP l 0 0 ,2 ng/ml.
Chc nng sinh hc ca PAP l xc tc cho s thu phn cc
monoeste ca axit photphoric trong tinh dch. iu kin hot
ng t u pH 4,5 - 6 . cn ch l PAP rt nhy cm vi
nhit , d bin tnh, cn xc nh hot tnh ngay sau khi ly
mu v ba qun mu trong iu kin lnh. Tri vi PSA, vic
sn xut PAP khng b anti - androgen km hm.
8 . P2 -M (Beta 2 - Microglubulin) l thnh phn chui nh ca
HLAI c mt hu nh tt c cc t bo cha nhn, c bit
nng d cao b mt cc t bo lympho. P2-M c kh lng
11,8 kDa v c phn lp nc tiu ca bnh nhn cha
protein niu. Bnh thng, ngi kho cng pht hin c
trong huyt thanh c 3,4 )ig /ml, nc tiu c 0,154 fj,g/ml.
Trong khi cc bnh nhn ung th dng lympho (bnh a
u tu, leukaemia), nng p2 -M tng cao, ch r thi gian sng
st ngn.
Trong cc trng hp bnh lnh tnh (vim cu thn, Vig thn,
bnh nhn AIDS , bnh nhn r lon chc nng min dch) ch
th p2-M cng l mt gi tr cn c coi trng. iu ng ch
l (32-M ca nc tiu km n nh, ph thuc vo pH.

152

Tm tt chng X

1. Min dch chVig vi sinh vt l mt c ch tng hp qua trung

gian t bo v c ch tc ng phn t ca cc sn phm t
bo.
2 . Min dch ung th nghin cu hin tng bt thng trong
sinh sn ca cc dng t bo min dch. Nguyn nhn (ii
truyn ca bnh l do s t bin ca cc gen gy ra hin
tng ri lon trong iu ho ca chu trnh t bo (ng ch
l gen p53 m ho cho protein p53 v gen p21 ras).
3. Mi loi bnh ung th u do mt khng nguyn c hiu qui
nh. Ngi ta cng pht hin c mt s h cc gen ca
khng nguyn ung th. Vic hiu bit cc khng nguyn ung
th c th gip cho vic phng nga v chn on ung th c
bit l ung th c ngun gc virus.
4. Tham gia vo min dch chng ung th gm cc kiu t bo
nh NK, LAK, cc i thc bo, cc t bo a axt v.v...
5. Hi chng tng sinh min dch l s ri lon v chc nng ca
cc t bo h thng min dch v to ra nhng sn phm c
bit l cc khng th n dng v cc protein c trng. Bnh
tng sinh min dch cng do nguyn nhn cc gen gy ung th
tc ng n chu trnh t bo c bit l s t bin ca cc
gen v cc nhim sc th.
6 . Mt s c im lm sng trong bnh dch ung th c ch
l cc ch th ung th (Tumour marker). s dng cc ch th
ung th dng pht hin sm bnh, tin lng v theo di
iu tr ung th c hiu qu nhm mc ch ko di thi gian
sng ca bnh nhn.

153

Chng XI. Min dch bnh l: thiu ht min dch

v hi chng suy gim min dch mc phi (AIDS)

11.1. Khi nim

S thiu ht min dch thng biu hin trng thi bt thng
ca mt, hay nhiu yu t ca h min dch dn n cc bnh l
khc nhau nh nhim trng v di khi dn n ung th. C hai
dng thiu hl min dch l thiu ht nguyn tliy hay bm sinh
v thiu ht th cp. Thiu ht min dch bm sinh do nguyn
nhn di truyn, thiu ht min dch th cp do yu t bn ngoi
nh thuc, chiu x, dinh dng km v do nhim trng.
V bnh l, ngi ta phn bit cc kiu thiu ht min dch
nh: thiu ht Ig hoc protein ca b th, thiu ht cc t bo
dng thc bo hay dng lympho T hoc lympho B.

11.2. Thiu ht min dch nguyn thy ca cc t bo B

Cc bnh nhn thiu ht min dch chc nng ca t bo B
thng b nhim trng ng h hp ti din i vi cc vi
khun vim phi cng nh cc bnh nhim ting ng rut.
Cc kiu bnh l do thiu ht t bo B l:

11.2.1. Bnh khng c y - globulin trong mu

Biu hin t bo v ha min dch ca bnh l: t hoc khng
c cc t bo B trong mu, hch bch huyt rt nh v khng c
hch amidan, khng c6 IgA. IgM, IgD v IgE v rt t IgG trong
huyt thanh. Ngi ta gi bnh ny l agamma globulin trong
niu do dt bin gen XLA, gen ny m ha cho mt protein l ti-

154

rozinkinaz c hiu ca dng t bo B. Mt dng bin i ca

bnh ny km theo s thiu ht hocmon sinh trng.
11.2.2. Thiu ht IgA, cc phn lp IgG v tng IgM
S thiu ht IgA thng gy nhim trng h hp v ng
rut v d bin chng thnh cc bnh t min. Gn 50% bnh
nhn b thiu ht IgA d xy ra hin tng sc khi b nhim
trng mu.
S thiu ht cc phn lp IgG in hnh nht l IgGs, IgG^ v
IgG4. S thiu ht ny lin quan vi nhim trng gy bnh m.
S thiu ht IgG v IgA km theo s tng IgM cng gy
nhim trng vi khun to m, tng sn hch bch huyt v gim
mnh bch cu trung tnh.
Nguyn nhn ca bnh l t bin gen m ha cho glycoprotein gp39, mt cu t gn ca CD40 (Xq27).
Cng c trng hp biu hin bnh gim y - globulin trong
mu (hypogamma-globulinemia) thng thng l gim hm
lng IgA huyt thanh. Mt s trng hp ca bnh trn l do
nhim virus Epstein-Barr.

11.3. Thiu ht min dch nguyn thy ca cc t bo T

S thiu ht min dch cc t bo T thng biu hin cc
dng bnh khc nhau:

11.3.1. S pht trin bt thng ca t bo ngun lympho

giai on sm ca s bit ha
Bnh thiu ht nguyn thu dng lympho T mang tnh di
truyn bm sinh, biu hin hi chng Di - George v c
chng minh bng th nghim ct b tuyn c, gy s pht trin
bt bnh thng ca dng lympho T. Bnh ny cn lin quan n
s thiu ht di truyn adeno'zin deaminaz. S thiu ht enzim
tri> ko theo vic tch ly cc cht trao i gy c cho t bo
ngun lympho nh dATP v dGTP. Cc cht c ny km hm
enzim ribonucleotit reductaz l enzim cn thit cho s tng hp
ADN v s nhn ln ca t bo.

155

11.3.2. Biu hin thiu ht cc phn t phn lp II ca MHC

Bnh th hin do thiu ht mt phn cc t bo l.vmpho T
C D - I* g i 3 r a s b t h o t c c g e n c a p h n t l p I I . M t s" d n g

hi chng thiu hl lympho T c km theo s bt thng biu

hin cc phn t lp I ca phc h MHC.
11.3.3. Hin tng mt iu ha gin mao mch do di truyn
theo thiu h t IgGv,
IgG, v IgA lm ml kh nng diu ha gin mao mch ca tiu
no v mt. V t bo lic v sinh hc phn t, ngi ta thy
Lhng xu3'n t gy cc nhim sc th 7 v 14 vng ca cc
gen TCR v Ig. T lin quan n sai st trong vic sa cha
DN.
n n h n y d o t h i u h t c c t b o T k m

1.3.4. Thiu ht cc protein kt dnh bch cu

Hi chng ny thng gi l thiu ht kt dnh bch cu (Leucooyte Adhesion Deficiency: LAD) lin quan n thiu ht biu
hin cc pi'0 tein mng di h P2 ca cc integrin. Integrin l

mt h cc glycoprotein mng c cu trc heterodime c chc

nng ch yu l kt dnh gia cc t bo, bn tron t bo v
ngoi bo. Nguyn nhn ca bnh l do cc t bin ca gen m
ha cho chui p (CD18), lm mt i s c mt cc dng hetcrodime C D lla/C D l8 . C D llb/C D l8 v C D llc/C D l8 .

11.4. Thiu ht min dch cc thc bo v b th

Dng thiu ht min dch thc bo thng th hin cc bnh
sau y:
- G i m b ch cu tr u n g tin h do h m s in h th n g ko theo d
n h im tr n g Staphylococus aureus v cc m m bnh g ra m m .
- S th i u h t b ch cu h t (g ra n u o lo p e n ia ) c n g g y ra m t s

bnh thiu nng ca hch cu a nhn nh gim kh nng ha

h ng n g v d i n g ca cc bch cu th c bo.

15(i

- S thUu ht cc yu t b th c bit l Cl-INH ko theo bnh

ph mch bi vi CI-INH th a m gia vo s iu ha tng th cc
phn t trong r ch ng mu v vim.

11.5. S thiu ht min dch th cp v AIDS

S thiu ht min dch th cp tliiig c biu hin cc
bnh sau:
11.5.1. C c b n h v m u v u n g th
l cc bnh v mu mn tnh dng B trong d c bnh
macroglobulin Waldonstrom, bnh u ty. bnh u lympho Hodg'
kin l do thiu ht qu mn mun. Cc bnh nhn thng b
nhim vi khun, virus ho.c nm vi sinh vt. Tuy dc dim min
dch th dch bnh thng nhng s thiu ht min dch t bo l
mt trong nling yu t d bo trc ng thi vic sn xut
ILIO t pht tng ln.
1.5.2. T h i u h t m in d c h d o r i lo n tr a o i c h t
Tnh trng dinh dng km protein thng gy ra s thiu ht
min dch th cp cc nc ngho. Hin tng ny gy ra s
bin i bt thng ca cc t bo T v lm tng t l globuin
trong mu.
Thiu ht min dch t bo c th gy ra bnh suy thn. Hi
chng h thn v cc bnh ng rut cng do s thiu ht min
dch km theo hin tiiR Rm y globulin trong mu.
11.5.3. B n h A ID S v co n n g l y tr u y n
Thiu ht min dch do HIV (Human Immunodeiciency Virus)
l loi bnh do virus gy ra s suy gim min dch cho ngi (
dc pht hin M trong nm 1981, n nay d lan ra kh) tli
gii. Theo d on ca t chc y t th gii (WHO). dn nm
2000 s c khong 26 triu ngi b nhim HIV trn ton th ii
v mi nm c khong 1.8 triu ngi trong s s cht v cn

157

b n h su y g im miii (lcli m c p h i (AIDS: A cq uiro d I m m u n o

D eiciency Synclrome) (lo HIV ^y ra. H in tng cc nc
c h u v c h u Phi li-OMK n h n g n m d u c a t h k XXI c n
b n h n h i m HIV c clu hng gia t n g . V v y c n phii c
nling bin )hj) khoa lic hu hiu v tin hnh nghin cu loi
th u c v vacxin c h iu (u (l n g n n g a s ti n t r i n bih
t r o n g cng d n g d n t'.
H IV c h a i loi k h c Iihau l HIV-1 (gy r a 98" b n h lan
tr u y n ) v HIV-2 chim u th v n g t y c h u P hi. L lan
U'uyii tr n th ioi. HIV l cc ro tro v iru s c b m y di I n iy n
th u c h L en U virus.
S l y I ru y n v ir u s c th Xiiy ra tlioo b n con n g s a u ly:

- Ccit t tim tn iy c n do d n g c h u n g k im tim ch ch nia ty.

- L y hini bai con n g tru y n m u ca ng i h n h cho
li khc.
- Con n g tip xiic tn h dc.
- Ly truy bnh t ngi m moc bnh sang thai nhi qua nhau
th a i.

11.5.3.1. Tin trin ca cc du hiu sinh hc v bnh l

S ti n Iri n c a b n h dc' t hoo di b n g cc d u h i u c a viru s , n h lng k h n th k h n g H IV v o cc th n g s lin
q u a n (ln s thiii h t m i n dch.
1.5.3.1.1. P h t hin viru s: p h t h i n v iru s. ngi ta do
protoin )24 lu hnli irong mu. (l )i-otein ch y u ca v CI)s it v iru s) |) h n lp v iru s t m u hoc t cc ly m p h o t u n h o n
b n g o rh nui cy l l)'io v:'i (lo p 2 l hoc (lo h o t n g tr a n s c rip ta z ngc tr o n dch ni c a mi tr n g nu i cy. Ngi ta c n g
s d n g p h n g p h p p h t Inn gonom ti n v ir u s ho c A R N virus bng cch kliuVli (li Cnzim trc tip hoc gin tip (phng

p h p P n iv R T -'('R ).
1.5.3.1.2. N q h u cu k h n g th ch n g HTV: Vic n g h i n cu
n y dc th c hM) bii^ k t h u l E LISA i vi cc p ro te in k h c
n lia u c a virvis. IMiicing |)h) Iiy dc s d n g t h n g t h n g d

l)hl h i n c<' doi tii c luiyl t h a n h d n g tn h . Ti) thoo l

k t h u l p li n tch c h u y n thm m i n dch p ro te in (W e ste rn blot) b t Inic c n ikic lp li di vi m u h u y t i h a n h i h hai.
S d n g k h n g tlie kh iu ig cc p ro te in c a lp v v cc p ro to in

158
D u hiu min dch: d u h i u q u a n tr n g l v i c g i m d n d n

s lng lympho T CD4 trong mu v mt s du hiu khc

n h a u n h t n g h m l n g P2 m ic r o g lo b u lin h u y t t h a n h . Ln:

noopterin huyt thanh v nc tiu, tng nng IgG v IgA

trong huyt thanh.
1.5.3. .3. Qu trnh tin trin ca bnh: Ngi ta chia lm l)a
thi kv tin trin bnh.
- Thi k s nhim: d i n ra trong m t s t u n n h i m H IV biu
h i n s l n g k h n g n g u y n p 2 4 t n g l n v k h n g t h khnf

p24 theo d cng tng ln, s p ng ca T gy c (Tc) cng

tng ln. Trong nhng tun u nhim HIV, s lng lym|)ho
T CD-I' gim xung nhng sau li tng ln.
- Thi, k th hai: k o d i t 1 d n 12 n m c g i l p h a kln!

c triu chng xiut hin, hay pha tim n. Trong thi k ny

s" liig kling th n nh mc cao, khng nguyn p2'1
thng kh pht hin nhng virus HIV c th c pht hin
bii PCl hoc R'P-PCR troig cc lympho ca mu v tron:
cc m bch huyt.
- Thi k th ha tip Ihoo xut hin khi s lng lympho T ('04'
g i m n h a n h xuVig di m c 2 0 0 t b o /m l m u . L c hi

chng lm sn ca bnh suy gim min dch xut hin. Trong

g ia i o n n y . n g i ta c t h p h t h i n k h n g n g u y n p 2 4 . ti

l phn trm cc t bo l) nhim virus v i khi c th thV

gim t l khng tli khii,' cc protein GAG (i)24, pl7). n<j
thi t l chung ca cc t bo T (T CD4*, T CD8 *) cng gim
xung. Hi chng suy gim min dch mc phi c xc nhn
bng s xut hin cc mm bnh nhim trng "c hi", S xu{l
hin cc khi u trn da Kaposi (Sarcome kaposi); l khi u
biu m mch, b ha sng c mu ta trn da. Biu hin
thi k tin AIDS c th l s"t, gim trng lng c th, m
hi bai m.
giai on AIDS, cc mm nhim bnh "cd hi" c th do cc
n']!! Candida, Cryptococus gy bnh phi, cc bnh Cryplosp o rid io se k m th e o a chy, cc b n h vim ph i do P s e u m o c y s tis
c a rin ii. n h i m lao M ic ro h a c te riu m , b n h t r n g b c h cu
(T oxoplasm ose), n h i m v ir u s tr n d a n h H erp es s im p le x , n h i m
Salmonella, Streptococcus. cc m m vi k h u n t o m phi,

xdng hoc mch mu..v.v...

159

11.5.3.1.5. Cu trc ca vrus HIV

L ipit kp
(m ng virus)
\

tra n s c rip -

11y S liip ro tein

v t ch
i

pr

p24

bc
cap x t

Hnh 11.1. S cu trc HIV (theo J.p. Revillard, 1994)

v virus c hnh thnh t lp lipit kp ging mng sinh cht

ca t bo, cha cc glycoprotein (gp) 120 kDa, bc l ngoi mng
v mt gp nh 41 xuyn qua mng, c hai phn t glycoprotein
u bt ngun t phn t tin thn gp 160. Gp 120 lin kt d
dng vi phn t CD4 ca lympho T CD4*. v capsit cn gi l
p bc gm bn loi protein p24, pl7, p9 v p7, u bt ngun t
prtein tin thn p53 kDa c m ha bng gen gag ca virus.
Cc c th b nhim HIV s sn xut ra mt khng th chng li
protein gag v p24.Bc capsit cha hai phn t ARN genom ca
virus v 3 loi enzim transcripta/ ngc, proteaz v integraz
(loi endonucleaz lp rp).
T chc genom ca virus gm 3 gen cu trc, ch yu chung
cho cc retrovirus, cng nh cc gen iu ha khc hau ring
c h o HIV. Cc gen cu trc l gen gag, to ra nhiu sn phm
pl7, p24, p7 v p9 lin kt vi ARN. Gen pol m ha cho cc enzim khc nhau nh p i o (proteaz), p66 v p51 (transcriptaz
ngc) v p34 (endonucleaz integraz) gen env m ha cho cht tin
thn gp 160 (gm gpl20 v gp41)

160

cc u tn cng 5' v 3' ca genom virus c cc trnh t lp

li o ngc LTR (long terminal repeats) cha ton b cc tn
hiu cn thit cho s phin m (transcription) ca provirus v
cho s gn kt vo cc gen ca t bo. iu ng ch l mt s
trnh t iu ha ca cc LTR cng ging vi cc trnh t iu
ha ca t bo. Cc gen iu ha l gen tat (trans activator) m
ha cho protein 14 kDa cn cho s ti bn virus. Protein ny tc
ng mc ca trnh t khi ng TAR nm trong vng LTR,
c chc nng loi b s km hm sao m. Gen rev m ha cho pl

20 kDa lm n nh v vn chuyn cc bn sao kch thc ln

mARN cn cc m ARN ny li m ha cho cc p l cu trc ca
HIV. Gen nef (negative regulator factor) m ha cho p l 27 kDa
(s c photphoril ha v kt hp vi axit myristic iu bin

s biu hin phn t CD4 ca mng t bo). Gen v if (virion infoctivity factor) m ha cho p l 23 kDa tham gia vo s chn v s
bin thi ca virus. Gen vpu c hiu cho H IV l m ha cho pl
16 kDa ng vai tr gii phng cc virion t t bo b nhim. Gen
vpx c hiu ca HIV2 v SIV (virus gy bnh AIDS kh) m
ha cho p l 14 kDa tc ng mc c hiu i vi vt ch
nhim bnh. Cu cng gen vpr m ha cho p l 15 kDa c vai tr
lm tng tc ti bn v hiu qu tc nhn bnh l ca virus
i vi t bo T.
11.5.3.1.6. Qu trnh nhim virus v chu trnh ti bn
Th th ch yu ca t bo vt ch i vi cc H IV l v HIV2

l phn t CD4. S tng tc virus vi CD4 th hin i lc

cao gia khu vc (domain) N tn cng D l ca CD4 v mt vng
o hnh thnh t 4 phn khng i ca phn t g p l20 . Phn
t gp l20 c hai vng rt ging cu to ca HLA-DR v mt vng
khc c cu trc ging khu vc VH ca cc Ig. S tng tc phn
t gp l20 - CD4 ko theo s ci t vng k nc ca gp41 vo
lp mng k nc v to ra s dung hp virus-t bo vt chMi mt t bo lympho T CD4* ca ngi c mt s lng CD4
nhim virus (khong 1000 phn t/ t bo (pht hin bng
Cytoluorometry- php o hunh quang t bo). Virus HIV c th
nhim d dng vo t bo vt ch nh cc con ng sau:
- Khng th chng gpl20 to diu kin thch hp cho virus xm
nhp t bo.
- Cc th th ca C3 (ca t bo thc bo. lympho B v t bo nang
V.thy) c th lin kt vi virus c opsonin ha bng b th.

161

- Gangliozylxeramit ca b mt mn? - '.lo (dng biu m rut.

m o) v t bo thn kinh c th( in kt vi phn t gp l2 0 .
11.5.3.1.7. p ng m in dch rh n g H V trong q u trin h n h im

Khng th: sau khi nhi.i virus t 3 n 12 tun thy xut

hin khng th trung h , tng yu khng li vng V3 ca
phn t g p l20 l khng chc chn {in vivo) v khng th khng
th phn hy c virion khi c mt b th.
S p ng ca cc lympho T CD4* vi cc peptit ca HIV
d dng nhn thcy v chnh s hot ha lympho T CD4 in vitro
gy ra s ti bn cc virus. Ngi ta cng thng bo s c mt
ca cc lympho T CD4 gy c c hiu vi cc peptit NEF v
nhiu cng trnh chng minh r lympho T CD4 gy c (tc
hiu vi g p l2 0 .
ng ch l p ng ca lym|)ho T CD8 * gy c xut hin
lc s nhim v tn lu lu di trong thi k khng xu't hin
triu chng bnh v chi bin i vo lc cu ca qu trnh bnh.
Cc lympho T CD8 * rt c th dng vai tr kim sot s ti bn
ca virus trong thi k khng biu hin triu chng bnh v c
th tham gia vo cc hin tng min dch bnh l.
S gim hot tnh CD8 giai on cui cng ca bnh AIDS
trng vi s vic cc t bo CD8 * CD57*^ b km hm do c t" t
bo gy ra.
11.5.3.1.8. S th i u h t m i n d c h do H I V v cc h iu h in
th i u h t m i n d c h

Tnh bt thng v s lng lym pho T CD4*.

Ngi ta thy c hin tng im s lng ln v gim nht
thi cc t bo lympho T 01)4*^ ca mu. Trong thi k lm sng
cha biu hin triu chiig hnl. lng qun th l bo ny
gim dn dn. Tip theo, cc phn ng qu mn mun gim
xung bt bnh thng in vivo. S tng hp IL2 v IFNy cng
giam. S ti bn virus ko theo hiu qu bnh l t bo trc tip.
T l cc t bo b nhim virus trong Lhi k cha c triu chng
bnh khong t 1/100 n 1/ 10.000 (trong mu) v trong cc hch
bch huyt c t l ny cao hn.
Mt c im quan trng l cc lympho T CD4* b nhim virus
r th dung hp vi cc lympho T CD4* bnh thng hnh thnh
cc t bo ln nhiu nhn, lm tng hiu qu bnh l. Hin
tng ny gi l Syncytium.

162

Mt c ch bnh l khc l cc lympho T CD4* b nhim c th

trnh din cc peptit virus kt' hp vi cc phn t HLA lp I s
l t bo ch cho lympho T gy c. Mt khc cc lympho T
CD4* khng b nhim c th nut cc phn t g p l20 ha tan (ca
virus) v trnh din cc peptit ch bin kt hp vi phn t
lp II, gy ra kt t cc phn t CD4 cng vi khng th khng
gpl20. Hu qu ca hin tng trn l to ra tn hiu mt ng
(anergy) v to ra ci cht apoptosis cho chnh cc t bo T.
*S bt thng ca cc i thc bo, cc t bo B v nhng t
bo khc:
S nhim virus vi cc t bo trnh din khng nguyn c
th lm yu i chc nng ca nhng t bo ny, ng thi to
iu kin cho s phn hy chng bi tc dng ca cc t bo Tc.
Cc t bo B th hin kh nng sn xut tng gama globulin
(IgG, IgA) v lm thay i t l cc di lp IgG khi b nhim virus. S p ng khng th chng li p24 chim u th lu di
trong qu trnh tin trin bnh.
Ngi ta cng thy r s thiu ht chc nng dit vi khun
ca cc t bo trung tnh, chc nng ca NK cng suy yu.
Tt c nhng s thiu ht min dch trn do HIV gy ra s
to iu kin d dng cho cc vi sinh vt c c hi xm nhp vo
c th ngi bnh.

163

Tm tt chng XI

1. Nhng s ihiu hl min dch bm sinh l cc bnh him thy

)hn ln do cc t bin gen m ha cho cc phn t c chc
nng ch yu ca h min dch.
2. S th i u h t c c Ig ko theo b n h n h i m tr n g .

3. Xhiu bnh thiu ht min dch s dc cha bng liu php

thp t bo ngun to mu. hoc liu php di truyn cho
kt qu tt trong mt s trng hp.
4. Ngi la phn bit s thiu h t m in dch th cp vi s thiu

ht min dch bm sinh. S thiu ht min dch th cp do

n h i u n g u y n n h n n h u n g t h b c h c u d n g B, c c b n h u

lympho Hodgkin. do trao i cht r lon, do nhim trng cc

vi sinh vt. c bit l virus gy suy gim min dch HIV.
5. Hi chng suy gim min dch mc phi (AIDS) ngi l do
nhim virus HIVl v HIV2, nhng ch yu l HIVl (98% lan
truyn bnh) S tin trin ca bnh c th chia lm ba thi k:
thi k s n h im , thi k tim n (ko di t 1 n 12 nm ) v
thi k hi ch n g suy gim m in dch vi thi gian ngn tnh

theo nm thng.
6. S dp ng m in dch chng viru s HIV trong qu trn h nhim
dc Lh h in bng k h n g ihd chng li cc glycop rotein ca

lp v virus nh gpl20, cc lympho T gy c, T C D 4\ c bit

l T C D S \
7. H u qu ca vic nhim viru s HIV l gy ra s th iu h t m in

dch, c bit l s giam bt bnh thng v s lng ca lympho T CD4' trong m u. gim chc n n g m in dch ca nh iu

loi t bo ca h min dch v gy ra p ng min dch th

dch bt bnh thng ca co t bo B. T dn dn cc
nhim tr n g c hi, xu"t h in nhiu bnh khc n h au .

165

Chng XII. Diirvg np mn dfcli vl3tfih t min

12.1. Dung np min dch

12.1.1. Khi nim

Dung np min d c h (immunological tolerance) cho php c
th trn h p h n ng vi cc Lhnh phn ca bn th n trong thi

k c th mi sinh ra. Ni mt cch khc nh c ch dung np

m in dch cc t bo lym pho c th phn b it c ci bn thn"
v (i k h n g piii (;a bn th n .
N h n g th n gh im u tin ca M edaw ar v cng s (1953)

cho bit khi tim cho chut non A cc t bo ca chut trng

thnh CBA s ngn cn s thi b mt mnh ghp da ca chut
ny trn chut A Irng thnh.
Cc k h n g n g u y n lio tan cng (' th to ra s d u ng np. V
d a lb u m in huyt Ih a n h b (BSA ) c tim cho th mi sin h s

ngn cn vic sn xut ra khng th chng li BSA th trnp

thnh. S dung np min dch cng c th dc to ra cc ng
vt trng thnh nhng i hi phi tim mt lng khng
ngu yn rt ln. VVoigle v cng s ch ng m inh rn g tc dng

ca khng nguyn nng thp s luyn tp cc lympho T.

trong khi , nng cao ca khng nguyn gip cho vic luyn
tp i vi cc t bo B v T. N h vy tn h phn ng cn mt
ng v t vi m t kh ng nguyn phn nh mi quan h hp
t;c gi cc t bo B v T trong vic s n xu t ra m t k h n g th.
M t p h n t k h n g nguyn c du n g np nu bn th n n
khng b ci b in b n g cc i thc bo trc kh i n c t! nh
din cho cc l bo lympho.

166

12.1.2. Cc c ch to ra dung np min dch

Ngi ta nu ra cc loi c ch" gii thch sa u y:

12.1.2.1. S yn lng min dch

Ngi ta thy r h min dch dung np vi cc thnh phn
ca bn thn c th v hin tng ny gi l s yn lng min
dch, Cc thnh phn ca bn thn ch c th tr thnh ch*t gy
min dch (immunogene) nu chng kt hdp vi cc phn t lp
II ca MHC. Tuy vy. cc phn t trong tun hon mu c th b
bt gi bi cc lym pho B, b ci bin v k t hp vi cc phn t
lp II ca MHC nhng nng thp s khng to ra i lc

gi tn hiu cho cc t bo T. Nhng t bo B thng xuyn

yn lng.
S yn lng min dch cng c th do khng c cc gen m ho
cho cc th th ca t bo lympho chng li mt s quyt nh
k h n g n gu yn ca thn h phn bn thn.

12.1.2.2. C c h loi b dng

Ngi ta c nhiu bng chng cho thy c mt c ch loi b
tt c nhng t bo c hiu vi bn thn m khng lm thay
i phn cn li ca kho d tr cc t bo lympho. V vy, chnh
cc khng nguyn ca bn thn (autoantigen) tham gia la
chn loi b cc dng. Thin hng c bit ca c th s sinh l
kh nng dung np nn trong qu trnh pht trin h min dch,
cc t bo lympho c mt giai on tip xc vi autoantigen

v gy ra ci cht cho cc dng lympho t phn ng. l c ch

loi b dng.
M t s bnh t m in ca ngi km theo s t n g cao nng

ca cc t khng th (autoantibody) c hiu gy ra bnh l. Tuy

n h in c n g c m t s' bnh t m in lin k t vi cc t k h n g th

nhng vai tr gy bnh ca cc t khng th khng r rng. Mt

s' bnh vim m n tn h kh ng k t hp vi cc t k h n g th c

hiu li do hiu qu bnh l cu cc lympho T- t phn ng.

Cc quan st lm sng bnh t min cho php phn bit s
khc nhau ca bnh nh cc bnh c hiu vi c quan hoc vi
m t bo (v d b nh vim tuyn gip, chng nhc c, b n h

Pemphigus v cc bnh t min h thng nh lupus ban rai

167
rc. Sau y l danh sch cc bnh t m in c nghin cu

(bng 12.1)
B n g 12.1. C c bnh t m i n c h y u (theo J.F. Bach 1993).
1. B n h t m i n k h n g c hiu c q u a n

Lupus ban ri rc.

Vim nhiu khp dng thp khp.
Hi chng Sjogren.
Thiu mu do b tan hng cu, bnh gim bch cu, gim tiu
cu t min.
Bnh x cng lp da b (Sclerodermia).
Vim da c.
2. Bnh t min c hiu c quan
C quan

Bnh t min bit r

Tuyn ni tit Vim tuyn gip

D dy

Bnh t min cn nghi

vn
Thiu nng b my sinh
dc

Bnh Basedovv
Tiu ng tui tr
ph thuc insulin.
Thiu mu Biermer
rut

Thn
C
Da
Gan

Hi chng
Goodpasture
Chng nhc cd
Bnh thp khp c.
Bnh Pemphigus
Bnh tri tc.
Vim gan c tnh
Vim gan mn tnh.

Bnh vy nn.

12.2.2. Cc t khng nguyn tham gia

Vic hiu bit cc t khng nguyn (autoantigene) ca bnh t
min c ngha rt quan trng, cho php hon thin cc xt
nghim pht hin chn on c hiu v d bo hng iu tr.
Ngy nay, ngi ta c gng nhn bit cc phn t khng nguyn
nh cc ngn hng bc l ADN b sung (c-DNA) trc ht l cc
opitop B v cc peptit kt hp vi cc phn t MHC c trng

168

cho bnh. Ngay c khi c c cc t khng th tng i o

hiu cho mt loi bnh th vic nghin cu nguyn nhn ca
b nh c n g gp n h iu kh khn bi v cc t k h n g th dti

nh c nh trn cng mt cu trc cng c th nhn bit cc

khng nguyn khc nhau. Chng hn t khng th chri
Laminin, chng colagen IV hoc t khng th chVig khng
nguyn bnh Goodpasture u c nh ging nhau trn cc lp t
bo y tiu cu thn.
Ngi ta cng nhn thy 4 autoantigen khc nhau c mt ti
cc khp ni t bo biu m, 4 loi bnh Pemphigus khc nhau

12.2.3. Cc nguyn nhn ca bnh t min

12.2.3.1. Nguyn nhn di truyn
Bnh t min do nhiu yu t gy nn: nh cc du hiu di
truyn, cc yu t" mi trng.
Hin tng di truyn bm sin h gy ra cc b nh tiu ng phv.i

thuc insulin, x cng mng thn kinh, bnh vim nhiu khj)
dng thp khp. bnh lupus ban ri rc....
Phn ln cc bnh t min l do kiu hnh HLA qui nh. Mi
quan h gia kiu hnh HLA vi bnh t min c th c gii
thch l do chc nng trnh din cc peptit ca bn thn HLA .
Mt s cc nghin cu mi y cng c' cho gi thuyt trn.
Mt nguyn nhn di truyn tip theo l nhng t thiu ht
bm sinh cc thnh phn ca b th nh C2, C4, CRl, (CD:,,r,)
chng hn 0,3% c s thiu ht d hp t dng C2; 40% c th
ng hp t b bnh lupus ban d ri rc. C th gen TNF v cc
protein sc nhit c vai tr ti0ng mt s bnh t min.

12.2.3.2. Cc nguyn nhn mi trng

Rt nhiu nghin cu cho rng cc vi sinh vt gy ra bnh t
min, chang hn virus bnh si, virus Epstein-Barr gy bnh
vim nhiu khp. Mycobacterium cng gy bnh vim nhiu
khp.
Ngi ta cn nhn thy s thay i ca cc vng a l kht'
nhau, nh t" c a (atopy) cng gy ra t l mc bnh t min
khc nhau. V d vng Bc bn cu c s lng ngi mc bnli

169

vim a khp, bnh tiu ng typ I nhiu hn cc vng khc.

Mi quan h gia vi sinh vt v bnh t min c th l gin tip
nhng tc nhn nhim khun thng gy ra cc bnh vim th
cp. V d bnh vim lot d dy thng lin quan n vi khun
Helicobacter pylori, triu chng lit nh kiu co tht do retrovirus HTLV-1 gy ra.

12.2.4. Cc c ch hiu qu ca bnh t min

12.2.4.1. Vai tr bnh l ca khng th
Nghin cu cc loi bnh t min cho php xc nhn r c ch
gy tn thng ca khng th chng li cc th th. Chng hn
trong bnh nhc c (Myasthenia), s c nh ca khng th ln
th th c th gy ra s ph hu chc nng vn ng ca t bo.
Khi lin kt vi th th t khng th bao vy tc ng ca cht
truyn dn sinh hc (Mediator), l ch"t i khng (antagoniste)
hoc thay .th cht truyn dn sinh hc ng vai tr hip ng
tc dng hoc hp vn (agoniste), kt hp Cnh trnh vo th
th, t khng th cng c th khng c hiu qu sinh hc. Tuy
nhin t khng th c .th iu bin th th khng cho' n bc l
trn m n g t bo. Cui eng t k h n g th-kh i k t hp vi th th
mng s kch thch t bo kt hp vi b th v hp dn t bo
git n ph hu t bo v m theo c ch gy c t bo.
Trong bnh u nng tuyn gip Basedovv, t khnlr th chng
li th th ca T S H s phn ng vi vai tr ca m t ch t hp vn
(agon ist) lm t n g AMPv ni bo v kch th ch s tn g hp

hocmon tuyn gip. Mt s t khng th biu hin hot tnh enzym (c gi l abzym) phn hu lin kt photptdieste gy tn
thng AND .trong bnh lupus ban h thng.

12.2.4.2. Vai tr ca lympho T t phn ng v cc xitokin

Vai tr gy bnh ca lympho T cha c chng minh trc
tip. Tuy nhin cc nghin cu v xitokin TNFa, ILi, ILe c
sn xut nhiu cc t bo mng ht dch trong bnh vim a
khp c n g gi vai tr du h iu bnh ca cc xitok in ny.

Nhng nghii cu v c ch v nguyn nhn gy bnh t min

c th gip cho vic i tr cc bnh t min. Chng hn ngi

170

ta ra phng hng tim chng peptit cng vi cc t bo

T, hoc ca cc th th dng T gy bnh kch thch in vivo s
p ng Tc chng li dng t bo bnh l.
Mt hng khc l dng t khng nguyn tng hp cnh tranh
vi khng nguyn bnh l ca c th trong lin kt vi phn t
lp II HLA. K thut ny c hiu qu khng ch phng nga
bnh m cn cha bnh cho mt s m hnh ng vt. Nhiu cng
trnh mi y chng minh cch iu tr cho ung mt dng t
khng nguyn s cho php loi b bnh vim no tu d ng:,
bnh vim khp colagen typ II v mt s bnh d ng khc.
Trong trng hp bnh vim no tu cch iu tr trn lm
xut hin cc lympho TCD4*. T||2 tit ra IL4, ILIO, chng li
hiu qu gy bnh ca lj'mpho T ||l, ng thi lm xut hin
TCD8* c hiu vi mielin, lm gii phng TGFp c hiu qu kin
hm khng c hiu i vi t khng nguyn.
Ngi ta cng ang nghin cu dng khng th n dng lin
cht km hm min dch cha mt s bnh t min trn m(
hnh ng vt. S dng khng th n dng cha bnh ch (0
ngi cng ang c nghin cu lm gim tnh si!ih mici'1
dch trong ng dng cy ghp m, cy ghp c quan v xc inh
c ch tc ng ca khng th trong cc bnh t min.

171

Tm tt chng XII

1. Cc c ch dung np t nhin di vi cc thn h phn ca bn

thn c tip thu trong qu trnh pht trin h min dch.
C ch ny biu hin mc khc nhau ca cc lympho T v
13 (c ch yn ln g min dch, c ch loi b dng, c ch km
hm ca lym pho T. s mt ng, biu hin s hp tc gia t
bo T v B trong dung np min dch).
2. C c bnh t min ngi bao gm nhiu dng khc nhau nh
cc bnh vim mn tnh, bnh ti nhim vi sinh vt, bnh t
min h thig v c hiu cc c quan.
3. Bnh t min l do nhiu gen gy ra, c bit chu s kim
sot ca cc gen MHC v cc gen b th.
4. Co y u t mi trng nh nhim tr n g vi k h u n , v iru s v yu
t c a c vai tr nht nh trong cc nguyn nhn gy bnh
t min.
5. Cc c c h h i u q u ca bnh t m i n n h va i t r c a k h n g
th, l y m p h o T t p h n ng, cc x ito k in c t h g i p cho vic tm
liiu bnh t min, tm ra phng hng iu tr bnh.

173

Chng XIII. S tin ha min dch ca cc loi

ng vt

13.1. M u
TliPO cc nghin cu v c sinh hc v tin ha, nhiu nh
khoa hc nh Grass. Devillipr (1965); Carrol (1988); Margulis,
S ch w artz (1988) cho rng, loi ngi v )hn ln cc loi ng
V't khc u ihuc v mt ngnh ln cc ng vt c dy sng
(('liordata). H min dch ca chng th hin ba c im sau
y:
1. S o m t m h c h biu m l y m p h o ( v n g h u li n k t vi
cc khe m a n g .
2. S c m t cc m t y lym p h o k t hp vi n g li u ha.
3. C k h Ii n g n h n bit ce khng nguyn ngoi la i (alloanti-

ene) v phn ng chn li chng.

Trong khi s khc nhau ch yu gia cc ng vt dy sng
v c xng sng vi cc ng vt khng xng sng l ng vt
khng xng sng khng c phn ng ca khng nguyn l vi
nit oh^t ha gii dr hiu kiu khng th immunoglobulin,
noi tr ng vt da gai (Echinodorma). Cc phn ng bo v
ca cc ng vt nh l)t bin, giun, thn mm, nhuyn th, cn
t r n g loi c u g a i c h n h t h i k li c n h a u . H n n a , m c d c s

pht hin hin tng thc bo ca Metchnikoff vo nm 1882

(lnf' vt ngnh da fiu (sao bin) Iihig s lng cc cng Irnh
nhin cu v Uiih niiii dc-h ca dng vt khng xng sng
vn rn hn ch v mang tnli le t cho cln nhng nm 60 ca
( h k 20. T u y n h i n n i n h c h n kh) ( A r t h r o ] ) o d a ) l n g n h

cln^f vt khng xng sVig chim 90"^ s" loi ng vt d bit,

s lng cc nghin cu v tnh min dch kh phong ph v tp
t ru ii theo l)a hn chnh: cc t bo ih am gia vo tnh min
(lcli, CU' I'h ha iai mi dch v cc |)h:in ng min (lch.

174

13.2. Kh nng min dch ng vt khng xng sng

13.2.1 Cc biu hin t bo ca h min dch

Cc t bo ca h min dch ng vt khng xng sng c
th hnh thnh theo hai nhm l cc t bo c nh v cc t bo
tun hon mu.
Cc t bo c n h i khi tp tru n g l i n h n g th n g rt hay
phn tn ton b c th. cc cn trng, cc trung tm sinh
mu thng c chc nng l ni sn sinh ra cc t bo tun hon
mu ng thi c c chc nng l c quan thc bo v l ni tng
hp ra cc p h n t k h n g k h u n . Ngi ta c n g m t cc
hch sinh mu cc loi rn nc thuc lp gip xc (Crustacea)
v nhuyn th (Mollusca). Ngoi ra cn trng cc t bo mng
bao tim tp trung li thnh tng m hch thc hin chc nng
m bo (endocytosis). rn nc c cc i thc bo c nh
thnh tng nhm t 4 n 5 t bo dc theo mch mu v khe
mang. Cc t bo tun hon mu xut hin ng vt chn
khp v thn mm, trong khi bch cu xut hin cc nhm
khc ca ng vt khng xng sng, cn trng c hai dng t
bo mu l t bo mu khng ht v c ht. T bo mu c ht
k iu 1 th am gia vo h in tng th c bo v h i n tng k t t

(coagulation), t bo c ht kiu 2 hoc c ht in hnh c th

to ra th so v cc bao bao vy vt th l v tng hp mt
phn lyzozim ca mu tiu ha vt l. Cc t bo c ht kiu
3 hoc dng t bo plasma - i thc bo cha cc th lyzoxom.

13.2.2 Cc cht ha gii ha hc

Tuyt i a s" cc ng vt khng xng shg u khng c
khng th. Nhng chng cng tng hp mt s dng phn t c
hot tnh c i vi vt th l hoc c mt s cht hip ng tc
dng vi cc t bo min dch, tham gia vo phn ng kiu
opsonin ha. Cc cht c i vi cc vt th l c mt ng
vt khng xng sng c th l cc lyzozim, cc phn t gy tc
ng phn hy mu ca ng vt c xng sng, cc cht gy
phn hy vi khun c thn mm, da gai, giun t l nhng pro-

175

toin c kch thc nh l 2.10' - 4,8.10' dalton. Mt s ch"t khc

nh m elanin c tng hp cn trng v rn nc c tc dng
chng li k sinh trng v cc tc nhn gy bnh. Hu ht cc
ng vt khng xng sVig c th tng hp lectin (agglutinine)
v cc enzim xc tc cho phn ng tng hp m elanin phi hp
tham gia vo c ch bo v min dch t bo. l nhng phn
t c kh nng to diu kin cho s nhn bit v/hoc lm kt
dnh nhng t bo ca vt th l. Chc nng ca cc lectin vn
cha dc chng minh y . Tuy nhin ng vt thn mm
ngi ta chiig minh cc lectin c th ng vai tr trong vic
nhn bit ci khng phi ca bn thn nh cc t bo mu ca
chng to lin kt gia cc th th trn mng t bo ca mt s
t bo mu l v cc t bo vt th l.
H thng phenoloxydaz (PO) ca ng vt khng xng sng
cng l mt dy phn ng a n hot ha prophenoloxydaz
(Pro PO) trong mu ng vt chn khp tip theo cc PO l xc
tc cho chui tng hp molanin. Chng hn s hnh thnh
quinon l hp ch^ gy c chng k sinh trng.
Cc hp cht glycan ho<^c ni c t endotoxin cng vi cc ion
Ciixi tham gia v o p h n ng k t t dch huyt (hemolymphe)
cc giai on u, c th so sih vi h thng b th ca cc ng vt
c v.

13.2.3 Cc phn ng min dch ng vt khng xng sng

Ngi ta thVy mt s' chl dng attaxin c cn trng ch c
hot lnh dil mt s dng vi kliun gram m trong khi cc cht
xecropin (ccropine) c ph dit khun rt rng vi cc vi
khun gram dng v vi khun gram m. S tng hp xecropin
dc cm ng tc thi bng cc mm bnh c mt trong h tun
hon mu ca cn trng (Inspcta).
Cc phn ng min dch qua trung gian t bo ca ng vt
khng xng c mt tt c:i ce ngnh ca chng. l hin
tig kt t (coagulation) vi s tham gia ca cc yu t' th dch
v t bo. ngnh chn khp, hin tng kt t huyt tng l
do s kt ta ca mt dng protein c hiu. Hin tng kl t
ri km theo vic bi tit v hot ha mt s" vu t ca t bo
lm bin dng cc t bo mu c ht kiu 1 v 2 to tip xc vi

176_____________________________________________________________
v t th l. gii phng cc yu t n h n b it ca h thcn^:

phenoloxydaz c mt cn trng. Kt t l giai on u ti"n.

giai on nhn bit ca phn ng min dch ng vt khi;
xng sng.
Kh nng thc bo c tlic hin bng cc tbo c nh v
cc t bo tun hon mu xy ra theo mt qu trnh tiig Ui
nh cc ng vt c xng Vig. Tuy nhin, nhng s tip >c
min dch lun c Ihc hin c tnh ngu nhin, rt him chu
ng theo kiu ha hng ng. Cc t bo ny hnh nh khtn^
c th th c hiu v khng c s tham gia ca globulin m n
dch. Nng lng tiu th dnh cho hin tng thc bo do
qu trinh ng phn k kh. S hnh thnh th bao (capsubs'
v th hch (nodulcs) l mt phn ng c bit c mt ng i
khng xng sng nh cn trng v gip xc nh rn nc d n
ra theo ba giai on. Giai on u l nhn bit khng ngu>ii
nh m t trn. Giai on th hai l tch ly t bo tiii
hon mu v chnh cc t bo ny l thnh phn ca the bo.
bao bc quanh vt th l (vt k sinh chng hn) hoc to ra .h('
hch trong Irng hp i vi vi sinh vt. 0 giai on ba (( tr
bo tun lioii mu i khi bin di su sc. to va lp v lm c
lp vt th l v loi b n ra khi c th cn trng. Trong 'i'
th bao v th hch, ngi ta lun lun thy c mt ec ciiYl
melanin. mt s cn Irng thuc b hai cnh (Diptera). cc l
bo mu ch c chc nng Lng hp m elanin v khng tham i:i
qu trnh hnh thnh th bao. Mt s cn trng k sinh trn 'c
cn trnR kho vo lc d trng tim cc ht v iru s A D N vo
h tun hon vt ch v gy km hm hon ton phn ng m ii
dch .ca vt ch. cho php u trng ca cn trng k sinh )';U
trin. l khi nng km ch min dch ca cn trng.

13.3. Kh nnng min dch ca ng vt dy sng v

c xng sng

13.3.1 Cc ng vt hi tiu
Ngnh c dy sng (Chordata) gm 3 ngnh ph l ngnli li
sng ui (Uroehordata) hay cn gi l ngnh c bao (Tunica a).

177
n g n h p h s n g d u ( C o p h a lo c h o r d a t a ) v n g n h )h c x n g

sng tin ho hii oa (Vertcbrata). ng vt hi tiu thuc v

rochordata l ngiih ph dy sng s khai. Mt s t bo mu
ca hi tiu c c dim ging amip v c chc nng thc bo, c
vai tr quan trng trong cd ch tit v dp ng min dch. T bo
mu ca Tunicata bao gm t 5 n 8 kiu t bo trong t
n h t c 3 k i u c th so s n h vi cc n g v t b c cao. l cc

tc bo lympho, cc t bo bch cu v cc t bo khng bo. Cc

t ho ny hnh thnh t do trong tun hon mu hoc hnh
thnh cc dm hch lympho kl h) vi m lin kt hoc c
tm t h y n g t i u ha, d c bit c n h i u v n g m a n g . H miii

dch ca ng vt dy sVig S( khai C dc im gn vi cc ng

v t k h n g x ng s n g n h n g d t i n h a h d n v c m t s c
i m g ing vi n g v t c xng sng. C h a n g h n T u n i c a t a c

cc d\i hiu b mt t bo Thy-1 giVg vi cc globulin min

dch ca ii vt c xns sng,
13.3.2 C c n g v t c x n g s n g b c th p
Cc d n g vt c x ng sng bc t h p l l) c k h n g h m h a y
c m i n g t r n (C yclostoniata) b ao ni c h p v c xem
nh ng vl srt khai nht ca clii;4 vt c XLtdng sng vn cn

st li. Loi c ny c trung tm lo mu sd khai vch ng tiu

h a v (i cc v n g s a u n y s x u t h i n lch v Uiyn c. Ngoi

ra rc loi c inin ti'n d xiit hiii tin thn (pronephros).

Lp c sn (Chondrichlhyes; in c dui. c mp v c chinK'
d c h min dch c cn li'( phc t) hn mc d vn cn s
khai, c (!ui ngi la thy c tuyn c s khai c phn bit
phii v v p h n ty v c mt. l lch vi )hn t y Irng v t j
d. Cc dng vt ny c kh;i nii< ihi b mnh ghp nsoi lai v
kh;i Iiii tng hj) cc khn< th. C dui l dig vt c xng
sng (lu tin c cc t !)o p l a s n ia ^nng (lng vt c v v chim.
13.3.3 c d i m m ion d oh ca c c lp c x n g
l/i|> c xcing c Ii<,niii ^V xut h i n i';Vt sm t di c si n h ,
liiih Uiiih nn 1()) C\ ()sloichth\'os hao om nhiu phn l) vii
cn t n ti c h o dii Iiay. lop n y Iiuin t; t l i y ti-mi i h n c li a
cc in l o m u \''1 Iihiu l !)<) l\ni)li( v c c cli i h c b o

178

melano tp trung thnh tng cng vi cc t bo c ht. Cc

t b o p l a s m a c n g x u t h i n n h i u t r o n g l l c h n h n g k h n g
t h y h c h b c h h u y t . So s n h vi c h im ngi t a t h y lp c

ch c mt c quan lympho s cp l tuyn c. Thn, lch, cc

to mu c tm thy mt s nhm c u nm cc khoang
sn ca u. Bao tim hoc cc tuyn sinh dc ng thi l trung
t m b i t h a v s i n h s n v l ni d t r cc d n g t b o m u .
V c t n h m i n dch t h dch lp c, n g i t a thV r s

tng hp cc khng th c khi lng phn t cao, kh gingvi

IgM c a n g v t c v. C t h l p r o t e i n m i n d c h giVig I g M '

ny c chui nng khong 70 kDa, chui nh 22-25 kDa c mt

huyt thanh cc loi c, tr c ming trn. Khi tim hng cu
nhm mu o ca ngi gy min dch cho c hp
{P etronizon m a r iu s ) , ngi t a t h y c s t n g hp cc p h n t

khng th c khi lng 320 kDa (9S). Cc Ig ny c 4 tiu dn v

75 k D a k t hp k h n g c ng h o tr vi n h a u v c c u t r c b c
h a i t h h i n 50% d n g x on a ( L i t m a n et al, 1970). c chiitic

(c sn), c ui ngi ta cng pht hin IgM dng pentam e (17

- 19S) v c n g c d n g i n o n o m e (7S). C c IgM c a c x n g c n g

dc phn chia thnh cc di lp, trong cc chui H|.i khc

n h a u v t n h k h n g n g u y n . 0 c t r ( Ic ta ru r u s p u n c t a t u s ) (cat

fish), ngi ta tm thy hai izotip chui nh L. phn lp c ph)

(Dipneusti), hai lp Ig khc nhau v tnh khng nguyn d c
pht hin l IgM pentame (H = VOkDa, L = 23kDa) v cc Ig
monome (H = 38kDa, L = 22 - 23kDa) v i khi c thm dng
IgN (Marchalonis, 1977)
T m li, m c d cc k t q u n g h i n c u v t n h m i n dch c a
c cho t h y m t s n t t n g n g vi n g v t c v n h n g c n g
c n h n g s k h c b i t c b n s a u y:

- Khng chng minh c ngun gc tuyn c ca cc t bf

lympho (khng cha cc Ig b mt). Do cha bit c hiu
qu ca s ct b tuyn c i vi s tng hp khng th.
- Cha c chng c v c ch t bo ca vic x l v trnh din
khng nguyn.
- c bng chng v s tn ti ca cc khng nguyn ca
MHC lp I v lp-11 c chp (Hashimoto et al.l990). [The
Fish iinmune systom, Acad. Press (Ivvama george & Nakcnishi
TtMuyuki (1996)].

179

Cc cht truyn dn sinh hc do cc t bo h min dch ca c

tit ra nh cc xitokin cng c bit n trn 20 nm trc
y. V d, khi c hi b nhim virus ca bnh nhim khun gy
chy mu do virus VHSV, ngi ta nhn thy trong huyt thanh
c xut hiu nhanh chng mt yu t c c tnh gihg intereron
biu hin hot ng cao nht sau 2-3 ngy c b nhim virus
(Dekinkelin v Dorson, 1973). Dng t bo mono ca c chp
(C y p rin u s carpio) v c tr cng sn xut nhiu yu t" gihg IL|.
Cc t bo lympho hn hp v cc bch cu ca c chp v c tr
khi b kch thch bng lectin PHA u c kh nng tit ra mt
yu t"c hot tnh tng t IL2.
Ngi ta cng pht hin c nhiu loi b th c mt lf<p c
ging vi C l, C2, C3, C4 v C8-9 ng vt c v. Khong 6
thnh phn b th pht hin c cho thy h thng b th
c tng i pht trin (ensen et al, 1981).
13.3.4. c i m m in d c h c a n g v t b i n n h i t
Ngay t i c sinh ngi ta tm c du hiu pht sinh
ca cc ng vt lng c (Amphibia). Cho n nay cc loi lng
c vn cn tn ti v c phn chia lm 3 b: b lng c c
ui (Urodelaj b lng c khng chn (Apoda) v b lng c
khng ui (AnouraA Cc loi b st cho n nay cng tn ti v
c chia thnh cc b: b ra, b c su-thn ln v b rn.

13.3.4.1. Tinh min dch t bo ca ng vt bin nhit

Nu nh c quan min dch s cp tuyn c ca ng vt lng
c c ui cha bit ho r rng gia phn tu v phn v th
cc ng vt lng c khng ui v ng vt b st, tuyn c
bit ho r rng gia phn v v phn tu. Cng tng t, phn
tu v tu trng lch ca ng vt lng c c ui vn
cha c s bit ho r rng. Trong khi ng vt lng c
khng ui, s bit ho cu to ca lch r rng v tng t
nh cc loi b st v ng vt bc cao. cc ng vt lng c
v b st. h thng cc hch v m bch huyt lin kt vi ng
tiu ho cng hnh thnh. c bit Urodela v lng c
khng ui u hnh thnh m hch amian mc khc
nhau. Ring cc loi b st, cc m hch lympho vng hu
hnh thnh r nt. Tu theo cc loi lng c khng ui, phn

ISO

tuy xuiig d c hiu h in mc cao i h p k h c n h a u , CU'

loi liiong CI k h n g dui. vic c t 1)0 t u y n c c n hi c thi'
hMi r sm t 1 - 7 n g y s a u k h i t h t i n h t h mi c k h n n f
i li ci- n n h h|) m t b o ng oi lai. i u n y cho t h y va'
r quan trng ciia Uiyn c kh nng min dch lai ghp t

'iKKi cua dM vt lng c. Phc h ph hp t' chc ca lng CI

k!in.r (lui cng e c dim tng i pht trin. Cc khn.
!r.:uy(''n lp II oa MHC biu hin lng c khng ui
'r! (ii'; khi (l cc kh n g Iiuyn l) I v II u biu h in b st .
I3J. .2. T i n h m i n d c h t h d c h c a n g v t b i n n h i t

khng th ing t Ig-M c tng hp ng vt lnj;

rM' \ : Ik st. Thm vo ngi ta miu t cc Ig c khi
|)hn t nh tdiig l IgG c mt cc ng vt lnK I-U'
l ri;,; r.i d ni I;Y ( d n g m on o m e) lng c k h n g (lui v ('(

liui o dng vl luii c khng ui, mt dng IgM hexame.

1^^ (nioiinme). IgX (polyme) thuc (Izotip IgM) d c miu l
Cc I^Y l a ng vl lng c khng ui c c tnh khn^:
nuyn gn ging vi cc IgG ca b st, chim v gn gin g IgA
cua (ing vt c v. cc ng vt bin nhit nhit, khng c cc
(lui lp (subclass') IgC, khng c IgE v IgD nh cc dng vt cc
l'ni li. tnh phn ng vi cc yu t' ngoi lai d dr )lit
ti in ( cc cln vt c xiig sng bc thp, mc d cn s khai
Iihung cii th hin kh nng tin ho ca cc loi dng vt
Xli (li). cc c ih (lng vt gi c tnh bn vng ca c tli v
qun the loi, nhn bit ric "ci bn thn" v thi b "(i
khii^ )h;ii ca han ihn". to ra diig lc tin ho c(! loi.

13.3.5 Dc im min dch ca cc loi chim

i:i.3.5 .1 C c c q u a n v t b o m i n d i c h
l:.:.n. 1.1 T i K a b riciu s

Khc vi cc loi dn vL c v, cc loi chim, c ml c quan

Min clcl (!c bit l li Pabricius. C quan min dch Iiy l uii
1(f(' t bo lyni|)ho B chn. Hn na, cc loi chim khng c cc
tin n bch huyt riii bit. Ti Kabricius l mt c quan lyin

181

pho c d n g ti nm ( vn g sau, pha trn hu m n. K hoang ti

dc ph kn bng khong 15 np gp s cp v 7 np gp th
Cp. Cc np gp ny clc vin bng mt lp biu m, cc t bo
nh y (t bo nim mc). Lp biu m che ph n h iu n an g lympho, c s" lng t 8G00 - 12000. Bao quanh n an g l m t m ng

liii mch lympho lo i cc hn. cung c'p mt s' ln cc t

bo lym pho. Trong cc nang ca l i Pabricius c m t lp t bo

hiu m kt hp vi cc nang lo ra lp ngn cch gia phn tu

v ph n v ca nang. Cc lp tu v lp v ca n an g cha ng
m t s t bo plasm a, cc lym pho v cc t bo hn g cu li (re cu lo cy tes). Ton b b m t ca vch ngn cc k h oan g ca ti c
din tch tng ng 10 cm - trong d c 10% l lp t bo biu
m lin k t vi nang. Ti P abricius dng vai tr va l c quan
lym pho tru n g ng va l c quaii lym pho ngoi vi v cha ng
c t bo p la sm a sin h k h n g th v cng cha ng cc lym pho
T, nm v n g ph thuc T ca ti [Glick et al (1956): Sorvri et
al (1975); M u rth y et al (1984)]. Cng tng t nh tu yn c. ti
F abriciu s ca g con c kh nng tit ra m t hocm on l bucxin
(bu rsin e) t cc t bo nm bin gii lp lu v lp v ca nan g

lyinpho
13 .3.5.1.2 T u y n c
T heo K en dall (1980). tu yn c ca chim bao gm t 12 dn 18
ih u tch b i t v phn b i xng bn cc m ch m u c. Mi

thu li c phn chia thnh cc thu nh c cu trc phn v

v p h n tu. Cu trc hin vi ca cc th u nh tng t nh
tu y n c c a ng vt c v. Tuy n h in , c n g c m t s c im
sa i k h c l tu y n c c a cc loi chim c chc n n g nh m t c
quan lym p h o ngoi vi bi v khong 7% cc t bo lym pho c
tu y n c l lym pho B (sau khi trng n). Hn na, sau khi gy
m i n dch, ng i ta t h y c cc t r u n g t m m m v< mL s t
bo s n x u t k h n g th. T uyn c ca loi chim ging ng vt
c v v c n g l m t tu yn ni tit. Dch c h it tu v n c c n g gy
cm n g b it ho cc l bo T. in vivo v in vitro.
13 .3.5.1.3 C c c q u a n ly m p h o t h cp c a c h im
Cc c quan lym pho th cp ca chim gm lch, cc hch nh
bch h u y t, m bch h u y t ca ng tiu ho, m bch h u y t cnh
m i. chim trvrng thn h, lch l c quan s n x u t k h n g th
(Ig) v t kch thc p h t trin ti a tron g 6 tu n tui u
tin. c bit lch ca chim c ml s o nh (mt s cm ) c
lp oa cc t bco B.

182

Nhn chung, cc loi chim khng c cc hch bch huyl ring

bit, ngoi tr mt s loi thuc h ngan ngng (Anseridea). Cc
m bch huyt y th hin l nhng hch nh (nodules) nm
ri rc theo chiu di mch mu, hoc mt s c quan. Tri li
m lympho ng tiu ho cc loi chim kh pht trin. l ti
Pabricius. m amian ca rut tt (manh trng) v cc tm
Peyer dc theo ng tiu ho. Ti Pabricius ng c hai vai tr'
(th cp v s cp) v vai tr min dch cc b i vi chim non.
M l y m p h o c n m i n m v n g g n m i v g n m t c h im . M'

ny c hnh thnh ngay t nhng ngy th 1 7 - 1 8 ca qu

trnh p trng l do s xm nhp ca cc t bo lympho xut
pht t nim mc (tuyn nhy) mt v cc xoang mi. Ngi ta
tm thy dy ch yu l cc lympho B v rt t lympho T.
13.3.5.1.4. Cc t bo c a h m i n d c h c h im

H min dch chim bao gm cc t bo lympho T v lympho B.

Cc lympho T cng c phn bit l lympho T b tr (T||), lympho T km hm. lympho T gy c v cc lympho T lin quan ni
cc phn ng (u mn mun. Cc du hiu b mt ca cc t bo
T cn t c sng t. Ngi ta s dng khng th n dng
v nhn bit c khng nguyn b mt CT;j, gn ging phc
h CD3 ca dng vt c v. Khng nguyn CT.I c m l khong'
20% t bo c v ch yu cha nhiu cc lympho ca l c h vi
mu.
Cc t vo B ph thuc ti Fabricius, khi U'ng n, c khonp
2x10. Cc t bo B nhanh chng phn chia ti v t s lng
gp i trong mt ngy. Tuy vy, ch khong t 1 n 10% s t
bo ny ri ti i v pha cc c quan lympho ngoi vi. Scn l i
b cht hoc bit ho in situ. Cc du hiu b mt ca t bo B
bao gm hai nhm l cc khng nguyn c hiu cho tt c o(C
lympho B. Nhm u tin c 4 loi khng nguyn b mt l CB1, CB-2, B3 v HNK-1. Khng nguyn CB, c th ng vai tn'
tng trng v lm chn cc lympho B. Khng nguyn CBv c
mt cc lympho v cc t bo biu m ca ti v cha r vai tn
ca n. Khng nguyn 13, c t bo B vng tu, cc t b(0
biu m rut v ti hu. Nu thiu B;j g b bnh thiu ht ganua
globulin tron^^ mu. Khng nguyn HNK-1 c mt cc t bo B
c a c q u a n l y m p h o ngo i vi v diig vai t i lm c h n cc lymphO
B ca ti.
Pink v cc cng s d s dng khng th n dng nghim
cu khng nguyii (hung cho cc t bo B v nhn thy chng

183

u cha cc Ig. Cc t bo cn li ca h min dch chim bao

gm cc i thc bo, t bo bch c<u ht (gm cc t bo a axt
gi: pseudo-eosinophile biu hin hot ng thc bo v vim,
cc t bo a axit thc th, cc t bo a kim), cc t bo tiu
cu, t bo mast, cc t bo NK v K (l nhng t bo c c tnh
ph thuc khng th: ADCC).
13.3.5.1.5. C c k h n g n g u y n M H C v n h m m u

g. MHC b a o gm 3 loci l B-F (cc khng n g u y n lp ), B-L

(cc khng nguyn lp II) v khng nguyn a hnh B-G (khng
n g u y n lp IV), c h c bc l tr n b m t h n g c u v li n k t

cht vi locus B-F. Nghin cu MHC ca g cho thy c nhiu

irn ging vi ng vt c VI v tnh cht a hnh, v cu trc
v chc nng v s biu hin t bo. Tuy nhin, ng vt c
v khng c khng nguyn B-G. Chausse v cc cng s
nghin cu vc.u trc phi. t ca phc h B v chng minh
tnh a hnh v di truyn c I cc phc h BL, BF v BG.
Vic pht hin vai tr ca cc khng nguyn lp I v lp II ca
MHC g cho php hiu c s bin dng di truyn ca tnh
chng chu mt s bnh ca g 1.
13.3.5.1.6. C c g lo b u lin m in dch (Ig)

chim, ngi ta tm ( 3 lp Ig l: 7slg, IgM v "IgA"

(tng t IgA) v khng pht hin c cc di lp, Ngi ta
cho rng I't c th c cc Ig g 1 ging IgD v IgE ca ng vl
c v. (Chen et al 1982).
- Chui nng ca 7slg c thm mt khu vc chc nng so vi
chui nng gamma (IgG) ca lng vt c v. H s' lng ca
7slg l t 7,3 n 7,4 s. 7slg l ut globulin min dch ch yu
ca huyt thanh, c nng t 5 n 7 mg/ml. ng ch l
c s sai khc nhiu gia 7slg v IgG ca ng vt c v.
- Cc IgM ca chim c khi lng phn t 890kDa v h s lng
17s. Do khi lng phn t kh cao nn IgM ca chim khng
th vt qua lp biu m ca vi trng v do khng c mt
non hong. C 5 allotip ( t M-1,1 n M-1,5) ca IgM nh
khu cc khu vc chc nng thuc vng CH khc nhau.
- Cc IgA "tng t" - c cu trc ging vi cu trc ca IgA ca
ng vt c v. Chng c nhiu cc cht tit v cc dch sinh
vt v tn ti hai dng (monome v polyme). Theo s lng
monome kt hp, h s lng ca cc IgA tng t bin i t
9 n 16s v c khi lng phn t t 350 n 900 kDa. IgA

184

ca chim tp trung nhiu mt (3 -12mg/inl) v c tit vo

khc rut t trng t l l,7m g/m l, ni c th chng li s
xm nhp ca vi khun v virus. Cc IgA ca mt chim cng
c mt mnh tit c khi lng 60 kDa. Mnh tit ny c cc
t bo gan tng hp v gn vi IgA trong qu trnh i t mu
vo mt.
13.3.5.1.7. Cc b t h ca c h im

B th ca chim cng c vai tr bo v th dch chng li

nhim trng. Ging nh cc ng vt c v, thnh phn C3 ng
vai tr quan trng trong min dch v l phn t quan trng
nht ca s hot ho b th. g, C3 c tinh ch, c khi
lng phn t 190 kDa bao gm hai polypeptit a v p, c khi
lng tng ng bng 118 v 68 kDa. im ng in ca chn
bin i t 6,4 n 6,6. Nng ca C3 t 0,4 n 0,5mg/ml v
bng mt na nng C3 c trong mu ca ng vt c v. C3
ca chim ging ng vt c v v cu trc v chc nng. B th
ca chim c th c hot ho theo con ng c in v con
ng lun phin. Theo con ng lun phin, yu t B c vai tr
quan trng khc vi yu t" B ca ng vt c v l c tnh n
hnh cao (BS, BF v BF/s), v khng kt hp vi tnh a hnh ci
MHC. Yu t" B l mt glycoprotein c khi lng 90 kDa v c
th tham gia vo s hot ho b th theo con ng c in.
Ngi ta cho rng yu t B tham gia vo phn ng tiu huyt
min dch (immunohemolysis) ging vai tr ca C2 ca ng vt
c v. Do C3 cng c vai tr ca C4 bi v ngi ta khng tm
thy C2 v C4 cc loi chim. c bt chim, ngi ta thy c
Cl- esteraz tc ng ln yu t
Hot ng cua b th c
pht hin ngy p trng th, 13'y t cc i vo khong 3
n 4 tn tui. Ngi ta cn cha bit r nhiu iu v hot
ng ca b th ca cc loi chim.

13.3.6. c im k min dch ca b linh trng

Nghin cu c im min dch ca b linh trng khng ch
gip cho vic tm hiu mi quan h tin h min dch gia cc
loi ng vt bc cao so vi loi ngi; ng thi cn ng gp
cho cc nghin cu y sinh hc thc nghim ca cc bnh loi
ngi nh bnh ung th, bnh truyn nhim, thiu ht min
dch trong c AIDS v cc bnh t min. Theo Sibley v Ahl-

185
g u ist (1987). 98% thng tin di truyn (genom ) ca ngi ging
cc loi kh cao cp C him panze, 92% ging kh th n g thng
lc a ch u P h i v 85% ging kh N am M.
Cc c im m in dch ca lin h trng c n gh in cu
rt k ti'ong n h n g cng trnh ca cc tc gi nh B en irsch k e
(1986) [P rim ates: the Road to s e lf su sta in in g pop ulation.
Spi'inger V erlag, N ew York]. K alter (1987) [M onographs in prim atology. V ol 2. A lan L iss, co. N ew York]. H in nay, b linh
t r n g b a o gm 13 h l: T u p a lid a e , D a u b e n to n id a e , In d r id a e ,
L e m u r id a e , L o risid a e , T arsiid a e, C a llitricid a e , C ehidae, Cerc o p ith ecid a e, Colobidae, H ylo b a tid a c , P o n g id a e v H o m in id a e .
(hnh 13.1).
(! th tm t t m t s c im quan trng v c quan m in dch,
tn h m in dch t bo v dch th ca b linh trng v mt s"
cif im ca chn g.
13 .3 .6 .1 . Tu x n g c a b l i n h t r n g
y l c q u an m in dch s cp, l ngun to ra t t c cc t
lio m u c chc n n g tun hon m u ca c th. Ln u tin,
cc- tc gi S ta s n e y J. v H iggin s GM m t th n h phn tu
xng ca k h R h esu s {M acaca m u la tta ), vo nm 1936 (The
l)one marrovv of the m onkey. Anat. Rec., (1936) 67: 219) v cho
l)it tu xng ca kh R h esu s gm 39% l cc t bo hn g cu.
r>3% l cc t bo bch cu a nhn, 4,5% l cc t bo lym pho,
(?% l cc t bo m ono. K hi so sn h vi loi ngi, ngi ta th y
kh R h esu s o s lng d tr cc t bo ngun to hn g cu ln
hn.

'I'u xng ca loi kh ui sc chu M (Marmoset) thuc chi

C a l li t h r i x c h n h t h i k h c th n g c n g h i n cu k h chi

tit. S biu hin ca MHC v vai tr ca n trong cy ghp tu

xng c n g h in cu.

186

Daubentonida' Indridae

Tarsiidae

Cercopithecidae

Colobdae

...................... 1

CalitrcidaeI Cebidae
'C.
'

J1

\
i

liobatidae

Hominidae

Hnh 13.1. Cc h thuc b linh trng hin nay (theo Kalter, 1987)

I3.3.G .2. M ith i d c h t b t o

T n h
h

Iv l) ( ) c u a (u t r n h p h t I n n c l l ( o n l o '
c u a loi kl { M a c a c a n e n i s r i n a ) (a (lic cc tc rix

n ii n
n sc.

i ! ( l

S c M k ( t i

\'

( M a k

114)H*!1 c u

ti'o n i

thi

187

<ly (Development of lymphocyte subset in pig - tailed macaque.

Human. Immunol. 1988, 21:33). Cc tc gi trn cho bit kh
mi sinh, cc t bo c hnh thi dy c v c du hiu khng
nguyn c trng cc t bo B IgD^, cc t bo T CD4*, Lp220*,
'P C l)8 \ Khi tui kh cng cao. du hiu tng ng i vi cc
lyrnpho c thay i, c th t bo B khng biu hin IgD (BlgD ),
T CD4', I.p220 . Ngi ta cng pht hin c 3 tiu qun th
T C D8 l TCD8* .CDlS'". TCD8'" CDIS"'"', TCD8", D18'"'.
iihii cha r s pht trin ca chng tng ng vi chc nng
(tc hiu min dch nh th no. Cc t bo TCD4*^ kh Macaca
Iriig thnh c s lng cao hn so vi kh cn non. c im
ny ging vi ngi nhng khc vi kh Chimpanze.
Chc nng p ng min dch ca cc t bo T v B kh u
ch (Babuoin) c n gh in cu v ngi ta n h n th y kh

ing ngi. Trong khi , khng c mt loi linh trng no th

liin p ng min dch mnh nh loi ngi.
Cc nghin cu khc cho thy cc t bo n nhn ca mu
ngoi vi (PBMC) ca loi ngi c kh nng sinh sn ti u khi
I' leclin kch thch nh con A hoc PHA. Trong khi , iu ny
khng th hin trng hp kh Rhesus.
13.3,6.3. T in h m i n d c h t h d c h

Tnh min dch th dch ca cc loi linh trng c

nghin cu trong nhng nm 60 ca th k 20. Ngi ta s
dng khng nguyn ngoi lai d chng minh s tn ti ca cc
globulin min dch nh gG, IgM. IgD, IgA, IgE trong huyt
Ihanh ca cc loi linh trng. Vic kim tra cc phn lp IgG,
cc tip kappa v lambda ca chui nh v tnh d th ca IgA
cng c thc hin trong cc nghin cu v c Damian
v c.reene tng kt dy trong ti liu ca h (The immumology of non human primates, in: RN Finnes, Ed. Pathology of
sem ian Primates Karger Rasel, 1972. tr.342).

188

C th a ra mt s dn liu so snh bng sau;

Bng 13.1. T l Ig huyt thanh ca ngi v cc ng vt linh
tring trng thnh, mg/inl (theo Demian v Greene, 1972)
IgM

Ig G

Ig A

C him panze

0 .5 9 - 2,4

1 1 ,3 - 1 8 ,0

0,97 - 2.12

Khi O rang O u tan g

0 ,2 0 - 0 ,9

10.5 - 13.3

0,90 - 1.9

K h u ch Babouin

0 ,3 0 - 1,8

1 1 ,0 - 13,3

0,1 - 4,1

Maccica rnuatta

0 ,8 0 2 ,0

12,0 3 0 .0

0.3 - 0,9

Macaca orctoides

LOO- 1,2

8.5 - 11,1

3.1 - 4,3

Ngi

0 ,6 0 - 1,5

7,7 13,5

1,8- 2,8

C c lo i

Cc nghin cu v thnh phn b th ca cc loi lin h trng

cho thy, k h n g h u y t th an h ca d k h n g li cc th n h p h n b
th ca ngi u c th phn n g vi t t c th n h phn b th

ca kh bc cao, ngoi tr yu tClq. Cc loi kh c chu Phi v

chu c c tnh thiu ht khng nguyn cc b th Clq, C ls
v C9. Cc loi kh Nam M thiu ht tt c cc thnh phn b
th, ngoi tr C5, C6 v yu t B ca propecdin. cc ng vt
thuc b bn hu (P rosim ia), ngi ta khng pht hin c bt
c mt thnh phn b th no trong huyt thanh, v chc nng,
hot ng b th ca cc loi ng vt linh trng c th so snh
vi loi ngi, tr cc ng vt bn hu. l ng vt bc thp
nht ca liiih trng.

13.3.6.4. Phc h ph htp t chc ch yu ca linh trng

Kh nng phn bit c "ci bn thn" v "ci khng phi
ca bn thn" l dc tnh quan trng ca tt c c th a bo bc
cao. Kh nng nhn bit ny c c l nh sn phm ca co
gon ca MHC (Gotze D. The MHC in man and anim als. Springer
- Verlag. Inc. New York. 1977). S phn bit gia "ci ca bn
thn" v "ci kh ng phi ca bn thn" c th c h i n d d n g

nh tnh a hnh ca cc sn phm gen ca MHC ngay trong

mt loi. Cc khng nguyn ca MHC ngay trong mt loi. (c
khng nguyn ca MHC thuc v mt h ln ca cc immunoglobulin, lun lun c mt b mt t bo. ng ch l tnh

189

da l'.nh c a cc s n p h a m
l do s t hp c a m t s^ lng c
gii h n c a cc gen. Cc*
c a \ \ ] C ngi v c h u l da dc
n cu chi li t [Daussot ^J.. l^la. M. com plexe m ajeui crhislocXimpatibilit de r h o m n i ( \ K l a m m a r i o n M d e cin e Sc ien c es ^aris
(19S5). Hood et al. Gcnos of llc m ajor h isto co m p a lib ility com ])l(\\
ol ilie m o u s e . A n n . Rev. I m m u n o l , 1983, 1: 529 - 568]. CC (ng
v t lin h tr n g , p h n ln cc cng t r n h n g h i n c u v M H C c
li<n q u a n n k h R h o s u s (M acaca m u l a t ta ) v k h C him )a n zo
{P a vtro g lo d yte s) .
L l,.6 .4 , L H th n g R h L A ca R h e s is
V? n ^ u n ^c, n h n g s n p h a m c a cc gen c a M H C Hh(s u s
(ci gi l R hL A ) d u d dc xc il v h u y t t h a i i h hc b n g
doc t n h c a t b o ly m p h o i vi k h n g h u y t t h a n h ngorii lai
nli (! n h c c h gy m i n dch cho i vi m t c th C a
c n n nit loi. T h e o ph(>n p h p ny, B a l n e r v cc cn: s ()
H L a n , c n g n h Noeb v cng s M xc d i n h (!i(*
k h o i n g 27 g e n dc kim t r a
2 \ocuA )hn bit n h a u v (li
li ip n . Cc locus n y r l ging cc lorus A v B ( a HLA lo) I
c a ngi. C ho cln nay. ngi ta (h a tm dt* locus Iiin.u
clg vi locus HLA-C r nil khi Khoss. P m n lch ho siiih
V;i cu t r c )hn l c a n l n g s a n hain c a cc gon RlLA lo)
clio h y c nliiu d c dim r t ging: c h u t v ngi. Cc k h n g
ntuvn n y c; l o t h n h t 2 chui ]K)li])cptil c khi
k[)j v 12 k l ) a . ( 'h u i ll Ung n g vi ].2 niici*oglol)ulin ( a
n^ii
Cc Sin p l m ( a cc ;on RhLA lp II c n g dc l t:i t
11)71. (r k liiu l lal. Hin iy n^ai ta gi l locus 1)[{ (lo
)h h]) vi s p h n loai (li vi vxv <^on l) II - H L A c a n^i.
t)o; n gcM D R ca k h r i
I)R r a ngi v chut v l)ao

gn 8 kh n g nuyn khc* nhau, ngi, bii r n l khn ^

ngi;vn ca D R. ngi ta cl tm ra khn g nguyn H L A -D v
c h n ^ m i n h r n g CV s n p h a tn on r a locais D d dc xc d n h
kli nu(M cy hn h|) c{\c l bo lym)ho. in ng vi c*( kln^
ng iv n ca 1)R. Cc
d]) n min (ch IR (m m uno R(*S)oise) (l dc m ta c h u
(l clc chng minh kh v
nriv nay l nhn<^^ vn ('a l) 11 dng vai ti quan trig lro i[
VJ( c m n h n c vi cc* bn h khc n h a u ngi v d n g vt.

X^i ta (n ^ tm diUic hai hoc ba ,cn trong chn^ c ( l

ih g R h LA . S;ou 1-a, cc
m lo cho cc yu l (*a l) the.

190

c bit l yu t a hnh Bf cng nm MHC. S c trnh

by hnh 12.2 l bn gen ca h thng RhLA nm nhini
sc th 6 v c so snh vi kh Chimpanze v ngi.
Lp II

Lpl

Ngi

D/DR

B
C2

Chimpanze

D/DR

C4
B

C2
L
Rhesus

Bf

D/DR

C2

H n h 13.2. Bn gen ca MHC ca ngi, kh

Chimpanze v Rhesus (Theo Balner, 1981).
13.3.6.4.2. H th n g C h L A ca C h im p a m e

H thVig ChLA ca Chimpanze cn t c nghin cu so vi

RhLA. Cc khng nguyn lp I ca ChLA c xc nh r v
gihg nh Rhesus (Jonker M. Van Vreeswij
1981). Vng DR,
hin nay cn cha bit r, nhng cc kt qu phn tch v huyt
thanh hc v nh phng php nui cy phc h t bo lympho
chng minh vng D/DR ca Chimpanze ging vi ngi.
Ngi ta cng chng minh r tnh a hnh ca mt s yu t
b th ca Chimpanze nh Bf, C2, C3, C6 v C8. Hn na, cc
nghin cu cho thy cc yu t' C2, Bf lin kt cht ch vi ChLA.
trong khi , cc yu t C3, C6 v C8 khng lin kt vi ChLA
(hnh 12.2). Mi y Mayer v cc cng s cho bit, cc gen
ChLA lp I c phn tch mc trnh t cc nucleotit ca

w,

191
ch n g. K hi s dng m u d (probe) A D N ca ngi m ho cho
v tr ca lp I, M ayer v cng s phn tch m t th vin gen
ca A D N ChLA tm h iu alen A v alen B v ch ng m inh

rng mt s alen ca ngi c nhiu c tnh ging vi cc alen

ca C h im p an ze. T cc dn liu trn, cc nh n g h in cu kt

lun rng, tnh a hnh ca MHC tn ti trc khi xy ra s

phn ho tin ho theo hai hng Chimpanze v loi ngi.
l.3.6.4.3. H thng CyLA ca kh Cynom olgus (M acaca facicularis)

Keever v Heise (1985) nghin cu MHC ca kh Macaca

acicularis, v tm ra t nht 35 c im c hiu khng nguvn
ca lp I CyLA. Cho n nay, ngi ta b it 14 c im

c cng nhn l ph thuc vo locus CyLA -A, 10 c im ph

thuc locus CvLA -B v 6 c im ph thuc CyLA -C. T ,
ngi ta nhn thy tnh a hnh ca h thVig CyLA ln hn h
RhLA v c cu trc ging vi loi ngi.
Tm li, vic nghin cu cc c im min dch ca cc ng
vt linh trng khng phi ngi hin nay l iu r^t cn thit
nh m tm h iu s tin ho m in dch loi ngi. N h cc k

thut sinh hc phn t v min dch phn t, cc nh khoa hc

c th iu ch cc xitokin, nhm nng cao kh nng iu chnh
cc t bo lym pho in vitro v in vivo. Cc k t qu n g h in cu
trn m h n h lin h trng cho php to bc ch u y n tip qu
gia nghin cu khoa hc c bn v ng dng thc tin y hc i
vi loi ngi iu tr cc bnh nhim trng, cc bnh qu
m n, un g th, s cy ghp cd quan v cc b nh th iu h t m in
dch, c bit l AIDS.

192

Tm tt chng XIII

1. S khc nhau ch yu gia ng vt dy sng, c xng sng

v ng vt khng xng sng l ch: ng vt khng xng
sng khng c cht ho gii ca c th kiu khng th kt hp
vi khng nguyn l xm nhp t bn ngoi. Trong khi ,
ng vt dy sng c cc m hch biu m lympho, cc m
lympho- tu kt hp vi mt s c quan nh khe mang hoc
ng tiu ho, ng thi c kh nng nhn bit khng nguyn
l v phn ng chVig li chng nh cht ho gii kiu khng
th s khai hoc khng th thc s.
2. Lp c xng l ng vt c xng sng bt u c c quan
lympho s cp nh tuyn c, thn, lch. Tuy nhin, cc c
quan ny cn s khai v ng lun c vai tr l trung tm bit
ho, sinh sn v d tr cc t bo lympho v t bo mu,nh
nhng c quan lympho th cp. Kh nng p ng min dch
c cng biu hin thp. Khng c bt k bng chng no ni
v c ch trnh din khng nguyn, v khng c MHC lp I v
lp II. Khng th ca c cng ch dng ging IgM nhng c
khi lng phn t thay i, cha phn thnh nhiu lp khc
nhau nh ng vt c v, nhng h thng b th gm 6
thnh phn, tng i pht trin.
3. Tnh min dch t bo v min dch th ca ng vt bin
nhit (ng vt lng c) c nhng tin b hn so vi cc
ng vt bc thp l:
- c c quan min dch s cp nh tuyn c, lch, tng t b
st v n g vt bc cao.
- c bit lng c pht trin phc h ph hp t chc lp I
v lp II v biu hin r b st.
- c tnh min dch th dch th hin r, bao gm mt s
khng th nh IgM, IgG, IgA tdng t, mc d cha c IgE
v IgD.

193

A. H min dch ca cc loi chim c tin b cao:

- c c quan lympho s cp bit ho r nh tuyn c v c

bit ti Fabricius, l ni bit ho ca cc t bo lympho B, mt
c quan ring bit cho cc loi chim.
- D c c quan lympho th c'p bit ho nh lch, hch bch
huyt, m bch huyt. Cc t bo min dch nh lympho T v
lympho B bt u c biu hin bit ho theo chc nng ring
bit.
- H MHC, cc khng th v b th biu hin r chc nng
min dch.
r>. ng vt linh trng khng phi ngi c h min dch tin
ho cao vi nhiu c im ging loi ngi; mc d cng c
mt s c tnh ring cho mi h v mi loi. Do cc kt qu
nghin cu h min dch ca linh trng s a ti nhng ng
dng thc tin sinh y hc rt to ln cho loi ngi.

195

Chng XIV. Phng v cha bnh bng liu php

min dich

14.1, Vi nt lch s

Da vo s quan st v kh nng chng chu bnh u ma

ca ngi b mc bnh ln u v sVig st Edward Jenner
Anh (1796) ch ra vacxin s khai t mn m ca b b bnh
u ma iu tr cho ngi. Ln u tin, cc th nghim y
to ra kh nng chng chu bnh ca ngi vi bnh ny.
Louis Pasteur (1885) p dng nguyn tc tim chng trn
cha lnh bnh di cho mt thanh nin tn l Joseph Meister
b ch di cn t trc. Ngy nay vic gy min dch tch cc
c gi l tim chng (vaccination) k nim pht minh ca
E. Jenner mang li hiu qu rt to ln nhm phng nga cc
bnh do c t vi khun v virus gy ra. Cc th h vacxin lin
tip ra i v ngy cng c hon thin v c xem nh cc
cht gii c t" (anatoxin). l vacxin ch t c t" bch hu
v un vn x l nhit hoc focmon, hoc vacxin t vi khun
nguyn vn b git, vacxin gim bt c t nh BCG. poliovac,
vacxin si, st vng, vacxin ch t cc tiu n v khng nguvn
(vacxin hepatit B). Nm 1967, t chc Y t th gii (WHO)
chnh thc t ra mt chng trnh tim chng m rng, c h
thng trn ton th gii nhm ngn nga nhiu bnh dch cho
loi ngi.
Vic pht minh ra c tnh khng c ca cc khng th chng
li c t vi khun bch hu ca Von Behring vo u th k XX
m ra hng s dng rng ri huyt thanh min dch ca cc
loi ng vt nh th, nga, cha bnh nhim trng. l
ngun gc ca liu php min dch (Immunotherapy), tc l
phing php cha bnh trn c s min dch. Hin nay, cc th
h khng th c s dng trong liu php min dch d ln lt

196______________________________________________________________
c ci tin. L c u l k h n g t h a d n g c a ngi dc t i n h
c h t h n hp h u y t t h a n h c a n h i u c t h cho m u . T i p th e o
l vic t o r a k h n g t h n d n g c a K o h l e r v c a M ilsto in
(1975) m r a k h n n g n g d n g t r o n g n g h i n c u y hc v
liu p h p m i n dch. N h n g t h h k h n g t h dn d n g n g y
c n g dc h o n t h i n n h k h n g th lai g h p g e n ca ngi v
c h u t (c h im a e ric h u m a n i s e d ro d en t m o n o c lo n a l a n tib o d y ), kliiiK
t h c h i u lng t n h (bispecific antibody)...
N g y n a y cc n h k h o a hc v y hc c n g n g h i n cu v
a v o n h i u p h n g p h p c h a b n h t r n c s m i n dch nlui'
liu p h p t bo, liu p h p gen, cc c h t k m h m , kch th c h
m i n dch v i u h o m i n dch c h a cc b n h n h i m t r n g ,
b n h t m i n , b n h s u y g i m m i n dch b m s i n h h o c m c p h i,
n g t h i li u p h p m i n dch c n g d n g t r o n g cy gh)
t h a y t h cc c q u a n .

14.2. Tim chng, vacxin phng v cha bnh

14.2.1. Nguyn tc chung ca vacxin

Tim chng (vaccination) ng ngha vi gy min dch ch
dng nhm gip cho c th c kh nng to ra ml c ch bao v
chng li s xm nhp ca mt c th xm lc hoc c t ca
n. Gy min dch ch ng hay tim chng l khai thc c tnh
p ng min dch s cp (sn xut ra khng th IgM c i lc
thp ban u) v dp ng min dch th cp (sn xut vi tc d
nhanh ra mt lng ln khng th IgG v IgA c i lc cao), To
ra kh nng ghi nh min dch nh tc dng ca khng nguyn
(vacxin) khi gp chng hng i th s p ng min dch s
c thit lp trong c th. Cc vacxin ng vai tr l nhn
khng nguyn gy min dch ch ng, thng l cc tc nlin
gy bnh c lm gim bt c tnh hoc lm mt hot dn
hoc l cc tiu n v (subunits) ca cc c t vi khun hoc virus. c im quan trng ca tim chng vacxin l phi dm bo
c mc an ton, khng gy bnh nhng to ra cho c th
tip thu c tnh min dch khi c tc nhn hoang di xm
nh). Hin nay. mi loi v a c x in c s dng u c nhng k h a

197

cnh li ch v bt li. C hng hn cc va cxin c (;h to Lheo

kiu lm gim mc d dc (poliovacxin) c s dng ihoo ng
ming, c li ch bo v v phng bnh tt v thng ch s dng
mt liu cn thit. Hn na vacxin s lm tng mc min dch
qun th v c th truyn tnh min dch t ngi ny sang ngi
khc. Tuy nhin, iu bt li ca vacxin kiu gim dc tnh c
th l s bin i c tnh d (ln n kiu hoang di mi v
va cxin lun lun phi bo qun lnh. Trong mt s" trng hp,
vacxin kiu gim c t cng khng th c dng cho trng thi
thiu ht min dch t bo T v tnh trng
thai nghn.
Cc vacxin c ch to theo kiu git cht tc nhn gybnh
c li ch l an ton cao. n dnh hn khi vn chuyn i xa v bo
qun d tr d dng. Tuy nhin, iu bt li l km hiu qu
hn so vi vacxin kiu gim bt c tnh, s' lng cc liu dng
n hiu hn v khng to ra c tnh m in dch qun th.

14.2.2. C c d n g v a cx in a n g c n g h i n c u v s d n g

14.2.2.1. Cc vacxin vi khun

Cc vi khun c th c git hoc lm mt hot tnh iu
ch tc nhn gv m in dch hu ch. V i k h u n c nui C'y in
uitro. Cc vacxin Vi khun bao gm:
a) Vacxin gim bt c tnh nh BCG(Bacille - Calmettt' Gue'rin) i vi bnh lao.
b) Vacxin gy bt hot tnh (hay vi khun b git);
- B o rd e te lla p c rtiiss is l VI ho g.
- S a m o n e la ty p h i v s .p a r a t y p h i di vi bnh st thng hn.

c) Vacxin l cc tiu n v hoc dc t:

- N e u r o t o x i n c a C L ostridium tetani l m m*t h o t t n h b n g

x l ha hc c iu ch vacxin un vn.
- c t c a C oryn ebactcriiim d ip h th e r ia e l m m h o t t n h
bng x l ha hc c iu ch vacxin bch hu.
- Polixacarit thnh t bo vi khun H a e m o p h ilu s in flu en zae lyp
dc iu ch vacxin vim mng no.
- Polixacarit thnh t bo vi khun N e isse ria m e n in g itid is A v
c c iu ch v a cxin vim mng no ty.

198_____________________________________________________________

Ni chung, ngi ta c th x l nhit, ha ch"t nh foomon.

phenol git vi khun cho mc ch iu ch vacxin.
C c v a c x in c i u ch c d n g t o n b t b o vi k h u n lin

quan n vn sn xut trong nui cy t bo c th a Vi

n h n g h i u q u p h t r i ngc k h n g m o n g m u n , T , ngi

ta nghin cu pht trin mt loi vacxin gm cc tiu n v

v t h n g gi l v a cx in k h n g c h a t b o ( a c e l l u l a r va cc in e s). V)
d . B o rd e te lla p e r tu s s is l tc n h n gy b n h ho g . c m t dc t

v mt cht ngng kt hng cu t b mt lng mao vi khun

(fimbrial haemagglutinin) c vai tr quan trng lin kt vi cf
t b o biu m c a v t c h. V a cx in k t hp g i a h a i loi p r o t o in
dc t i n h s c h t r n v lm m t h o t t n h l m t d n g

vacxin mi c nhiu u th. Tng t nh vy, ngi ta sn xul

ra mt loi vacxin st thng hn khng cha t bo bt ngun
t polixacarit v t bo Vi (tc l khng nguyn gy c Vi).
Mt loi vacxin mi c gi l vacxin Hib. c diu ch l
p o l i x a c a r i l v vi k h u n H a e m o p h i l u s in fu e n z a e t y p 1) k l hp v

protein c t" un vn (tetanus protein). Vacxin ny c hiit qua

ln, n g n c h n b n h n h i m
t h n g g y t l t von g cao.

tr n g H a e m o p h ilu s

m e n in g itis ,

14.2.2.2. Cc vacxin k sinh trng

K sinh trng l nhng c th a bo v k sinh nhiu vl
ch trung gian trong vng i ca chng. Thm vo nhiu k
sinh trng lun lun thay i c ch tinh vi nhm trn thot s
p ng min dch ca vt ch. l nhng vn kh khn
cho vic iu ch mt dng vacxin k sinh trng. Bnh st rt do
k sinh trng P la s m o d iu m sp. Hng nm git cht 1,2 triu
ngi v lm ly nhim bnh n 800 triu trn th gii. Bnh
sn mng S c h is to s o m a lm ly nhim 200 triu ngi, bnh ng
hay bnh chagas Nam M do cc k sinh trng T r y p a n o s o m a
cru zi ly nhim cho 12 triu ngi v.v... Do s nghim trn.
, ngi ta cn phi ch to ra cc loi vacxin k sinh trng.
c mt s s kin dio thy rng vic gy min dch chii
li cc k sinh trng c nhng kt qu nht nh. Trong nhn^
nm gn y, ngi ta t c nhng tin b quan trn
trong lnh vc iu ch vacxin chng bnh st rt. Bng chn^^
cho thy l cc t bo T gy c (T^.) c kh nng git cc k sinh
trng mc gan. Trong nm 1991 Hill v cc cng s (')

199

Oxford chit xut ra cc peptit khng nguyn t rnh ca cc

phn t HLA - B53 lp I qun th ngi Gambia chng chu
ic bnh st rt c tnh. Cc kt qu nghin cu chng minh
rng qun th Gambia chng chu bnh st rt c tnh c xut
hin s p ng min dch ca t bo T gy c HLA-53 vi peptit khng nguyn ca cc k sinh trng st rt LSA-1 (Liverstage specific Antigen-1: khng nguyn c hiu giai on
gan). iu ny gi cc nh khoa hc iu ch mt loi vacxin
trn c s cc peptit t LSA-1.

14.2.2.3. Cc vacxn virus

Cc vacxin virus c iu ch cc dng virus sng nhng
gim c tnh hoc dng virus b git hoc cc tiu n v
khng nguyn virus.
- Vacxin sng lm gim c tnh nh vacxin st pht ban,
vacxin bi lit (poliovac-Sabin), vacxin quai b, bnh si.
- Vacxin virus b git (lm bt hot tnh): vacxin bi lit dng
tim (vacxin Salk), vacxin cm. vacxin ch di.
- Cc vacxin gm cc tiu n v; vacxin hepatit B, vacxin cm.
Mt nguyn tc c bn cho vic ch' to vacxin gim c l cc
virus ARN d dng c lm gim dc t ldn so vi virus ADN v
ARN d c kh nng b ml hot tnh. Do vacxin ^iam dc t
ch c th c p dng cho cc virus d dng mt hot tnh v
chc chn b mt hot tnh,
to ra cc vacxin gm cc tiu n v khng nguyn, ngi
ta cn hiu bit v chn phn khng nguyn ca virus gy ra
p ng min dch ca t bo T v v tn' hay ch khng nsuyn
to ra cc khng th Lrung ha c iu qui nhiYl. C th l
khng th trung ha c khuynh hng nhm vo cc protPn b
mt ca virus, trong kii d cc t bo T p ng nhm trc tip
chng li cc thnh phn bn trong virus. Thm vo , cc Liu
(Jn v trong vacxin cn phi (' mt tt c cc chng ca virus
th vacxin mi c tnh vn iinR.
Trong mt tn< liii khng xa, vic s dng CII ngh* ti t
hp ADN c th da ti S i i i i xul mt s Va c x in c tnh an lon
(:K), nlit l ti-ii!i (lc c ln h ca viru s. Cc VK^xin ti l h(i|)
C'() I h d c

(ii d' Siiii x u l v a c x i i i <m c c l i e i i (lin v c a

k h ii n.mi\!i (c th l vacxin chnK l)nh st rt, v chnt v Tmii

iraii sivi VI liii). kliac phc iliic kh khn phi nui cy I

200

bo. Cc vacxin ti t hp c th c ch to phi hp cc tiu

n v c chn lc, nhm to cho vacxin c epitop u th min
dch, o th kt hp vi da s cc allotyp ca HLA lp II d kch
thch p ng cc t bo T b tr (T||), cng nh kt hp vi cc
phn t HLA lp I kch thch t bo T gy c CD8, hoc to
ra cc khng th trung ha theo muVi.

14.3. Liu php min dch khng th

K h n g th n dng c l hp t chui bin i ca chut
kt hp vi vng khng bin i ca khng th ngi c gi l
cc khng th lai ghp CD R (t ch: "vng xc nh b sung";
C o m plem en tarity D eterm in in g Region). y cc gen ca v n g
xc nh b sung ca khng th chut lin kt vi khng nguyn
(cc gen ca V|| v V |) c ghp ni vi cc g en C |1 v C|. ca
ngi v c bc l trong mt vect. Sau ngi ta a vo cc
t bo ng vt c v tng hp ra k h n g th la i g h p c h ai
ngun g c g en (C h im a eric H u m a n is e d R o d e n t M on o clon a l A n tihody). K hng th lai ghp hai ngun gc gen iu tr c h iu
qu bnh vim khp mn tnh.
M t d n g k h n g t h k h c l khng th h a i c h c n n g c h i u
(bi-specifc a n tib o d y ). Cc k h n g t h n y c h a i c n h t a y lin k t
c hiu vi hai khng nguyn khc nhau. Mi mt v tr lin kt
k h n g n g u y n c t h n h m vo m t loi k h n g n g u y n u n g th .
V m t s k h n g n g u y n u n g t h c n g c t h bc l cc m l
bo bnh thng nn vic lin kt lm tng gp i kh
n n g n h n bit, lm t n g t n h c h i u lin k t c a k h n g th.
Ngi ta nhn thy hu nh tt c cc t bo ung th mu c
tnh c bit l cc t bo plasma c tnh u mang du hiu
kh n g nguyn in h n h nh C D 19 v C D 20. M t s lym pho T
u n g t h c n g b i u h i n c m b it h a b m t CD 2 5 m c cao,
N gi t a s d n g cc k h n g t h n d n g m t t n h c h t
v nhn bit s khc bit ca cc cm bit ha khng nguyn
ny. Cc k h n g th n dng c th c cn g hp vi ch t ng
v p h n g x l o d
t r o n g li u p h p m i n d c h p h n g x, h o c
cng hp vi cc c h t c n h r ix in (lectin t R i c i n u s c o m m u n i s )
hoc c t bch hu, trong liu php min dch c t. Cc
khng th nh vy c th c xem nh l nhng "u n thn

201

k", c th tm dit cc t bo ung th v cc t bo lympho t

phn ng trong cc bnh t min.
Hin nay, vn s dng khng th n dng kiu u n
thn k mang cc c t vn cn ang c th nghim lm
gim bt c tnh ca phng php ny. Thm vo , cc khng
th s dng c ngun gc khc hu nh d tp trung mc
gan v lch. Cc cht c nh rixin c bn cht l glycoprotein
cng c hp th gan, c th gy c cho gan. trnh iu
ny, ngi ta ang th nghim vi cc cht c khng cha cc
gc ng.
Cc c t min dch kt hp mnh Fv ti t hp (Recombinant
Fv im m u n otoxin s) l

m t sn phm ca cng n g h t i t hp

ADN v cng ngh khng th rt mi y (t 1994 - 1998)

c s dng th nghim lm sng chVig li cc khi u rn, cc
bnh ung th mu (Leukemia, lymphoma, cc bnh Hodgkin)
ngi.
Theo Reiter Y v Pastan I (1998) cc c t' min dch ti t
hp bao gm cc mnh khng th n drg Fv (mnh Vj, V l
ci bin) c kt hp vi mt c t" vi khun rt mnh l
exotoxin A ca vi khun P s e u d o m o n a s (vit tt l PE). tng
thit k im m unotoxin ti t hp xut pht t c s l nhiu t
bo ung th bc l qu mc khng nguyn ung th c trng
(sn phm ca Oncogen) trn b mt t bo ca chng v thuc
min dch chng ung th cn phi nhn bit c hiu loi tr
t bo ung th m vn gi nguyn vn cc t bo bnh thng.
Do , mt na phn t ca c t min dch l khng th nhn
bit c hiu t bo ung th v mt na khc l cht c PE.
Cht c PE l mt protein cha 3 khu vc: Domain I gm cc
axit amin l-> 252 lin kt vi th th a2 - macroglobulin c mt
c t bo ung th v t bo bnh thng: Domain II (gm cc
axt amin 253
364) c chc nng cho php lm chuyn ri
phn trnh t cui c (gm on trnh t axit amin t 280 -> 613)
vo phn xitosol ca t bo. Trnh t cui c ny cha domain III
(bao gm cc axt am in t 396
613) khi trong t bo s tham
gia vo qu trnh ribozyl ho yu t ko di F -2cng vi ADP, lm
ngng s tng hp protein, gy cht t bo. Dng cht c PE -38
l PE b ct xn domain I v phn trnh t (gm cc axt amin
365 ->379) ch c tc dng gy c nhng khng nhn bit t bo
d d n g c s n x u t ti t hp trong E .coli v c d u n g hp

202

v di truyn vi mnh khng th trc tip chng li khng

nguyn ca cc t bo ung th. T , c t min dch ti t hp
c tnh chn lc v tm dit t bo ung th c hiu qu. Mnh
k h n g th c s n x u t ti t hp trong E .coli c n g l k t q u a

ca nhng cng trnh nghin cu v pht trin mnh m ca

cng n gh ti t hp k h n g th n dng t nh ng nm 1991 n

1996 (Winder, Milstein, Raag, Whitlow, Reiter, Pastan). Sau k hi

th it k gen sn xut c c mnh scFv, dsFv (ch bao gm V|| v V |,
lin k t vi nhau bng m t peptt nh hoc bng m t cu d isu n fu a ),
cc m nh kh ng th ti t hp c dung hp ''i phn tn cng N
ca PE - 38. Cc vecto biu hin c t m in dch scF v hoc dsFv l

mt plasmid c s lng bn sao ln, <; Studier v Moffatt

thit k v m t t nm 1986. Cc khng th ti t hp ang c;
nghin cu cho liu php min dch ung th trnh by bng 14.].
B n g 14.1. Cc ch cho liu php min dch (Reiter, Pastan 1998)

K hng nguyn

K iu k h n g nguyn

Dng ung th

ung th
CD 19/20/22

K h n g th

thit k
RFB4

Cc k h n g nguyn bit ho

L eukeniia t

ung th

bo B

T h th EG F

T h th

V, no, phi

e rb B 2

T h th c hiu ung th

V, d dy

e23

Leukemia t

Anti-Tao

/ O nco gen

T h th IL-2

Th th bc l qu mc

boT
T h t h lL - 4

T h th bc l q u mc

Th th IL-6

T h th bc l qu mc

Thn

u tu ,

m ie lo m a

Lewis

Th th EGF
t b i n

K h n g nguyn p h t tri n

V, d dy,

C a c b o h y d ra t

ru t k t

Th th c hiu ung th

G a n , no

/ O nco gen

B3, BI

M R l , Y IO

2 );

Cc mnh khng th ti l li) cn c ng dng cho vic

p h t h in v dit t i t bo ung th kl ch n g dc k t hp vi
cc cht nh dVu phng x nh lod'-*

hoc F''^. Chng liii

ngi ta iu chc m.nnh khng th dsFv nh du F'' v l'"
lt ngun t khng th anti-Tac. Xh chng ta bit, khng
th anti-Tac nhn bit v chng li tiu dn v a ca ih th L-2
c mt nhiHi l bo un th. Uu dim ra minh dsFv l c cu
trc nh nn phn b v thni lt nhanh vo cc khi u mang
th th IL 2. Do c th iht hin Iihanh cc khi u c kch
thc rt nh. Hn na VIC s dng liu php min dch phng
x ph hu t bo ung th bng cc manh khng th ti t hp
n h du uni; th (lc hiu cao c ih loi b c cc khi u nh

v t bo un- Ih. t gy c VI nhiig t bo bnh thng.

Mt phng php mi khi s dng I'c mnh khng th li t
hp l liu pluip khng th kt hi) onzim v thuc tin thn
chVig ung th. l k thut ADKPT (antibody - direcled
c*nzyme - prodrug therapy). Trong phng php ny khng th
ti t hp c cng hp ban u vi onzim v a vo c th d
nhn biL cnp nh nh v cc t bo ung th hoc dch ung th.
Sau cc lliui; Lin thu dit t bo ung th (prodrug) khng
c h oi tnh s c cc k h n g ih cng hp en zim bin thn h

thuc c hoi tnh v hu (iit t bo ung th. Enzim trong phc

h khnt th enzim c tc dng khuych i dc hiu lc dng
chng ung th ca thuc ti cc dcl ung th. K ihut ADKPT
c ng dng ( h\t dit cc t bo c biu hin th. th
EGF v th th crB2, ml s khng nguvn ca cc l bo ung
th biu m (Carcinoma, melanoma). V d phc h dsFv - p laclam az c iu ch ch("i'ng li t bo ung th c th th crbB2 c
hiu (u cao hu dit t bo ny khi n lm bin (li Lhuc tin
thn cephalosporin - doxorobixin thnh (loxorobixin.
Liu php khng th tl phng lint buc l khng th anti - D|
c tim cho tt c )h n Kh(d) niani Lhai nhi c khng
nguyn Rh*(D). Khng th ny s opsonin ha hng cu ca thai
nhi chy vo mu ca tn v loi b chng v ngn cn s tng
hp khng Lh anti - D (i c th m.

2 0 4 ______________________________________________________________________________________

14.4. S dng cc thuc km hm min dch

Cc thuic km lim min dch trc tin l cc Coi-lico.sU'i-()id,
l cc gluco corticosteroid nh cortizon, hidrocortizon. protinizon v prednizolon dc s dng c hiu (u kim sot S
p ng min dch gy vim tn thrtng trong ihc hnh lm
sng. Hydrocortizon xucxinat tan dc trong nc, dng tim vo
tnh mch, trong khi )rodnizon c dng dng ming v c tli
bin di thnh prednizolon nh cc enzim ca gan.
Hiu qui tc dng oa cc glucocorlicostoroid l: ihn (iin
cc th th t bo cht, thuc dlc c-huyen ti nhi t )o, lm
ci bin s biu hin ca gen, to diig ch yu ca steroid tlii
chc nng min dch lin quan dn mc d lil cc xilokin. ()
liu lng s dng dc l. glucocorticosteroid km hm s iai
phng TNFa v IL-1 t cc t bo mono, lm gim s lng h)
IF'N - y v IL-2 ca lympho T. liu lng s dng qu ngnj
dc l. in vitro, thuc c tc cinK km hm qu trnh t h c bo
ca t bo mono v km hm kh nnt t vi khun ca chiiK.
Ngi ta khng th qun tc (lng ph ca thuc sLeroicl l lm
tng kh nng nhim trng, km hm s siiih trng ca tr (111.
lm tng ng huyt v tng huyt p.
Mt s hot cht sinh hc cng l nhif chiVl km hm miii
dch nh cyclosporin v taorolimus. Cyclosporin l s;in )hm ca
nm T o ly p o c a d e iu m inlatiu m d dc xr nh du tin vo
nm 1976 trong khi tuyn chn cc tc nhn khn sinh. Sau
ny chng thng c s dng rng ri trong thc hnh lm
sng. Cyclosporin v tacrolimus (t nm mc S tr e p to n iv c e s tsukuhaensLs) mc d c cYu trc khc nliau nhiig (u lin kt vi
cc protein ni bo l immunophilin. Cyclophilin l
ca
t bo cht lin kt vi Cyclosporin, ngy Iiay d dc xc dnli l
mt enzim c tn gi l peptidyl prolin cis - trans isom eraz (hoc
gi l rotamaz). Trong khi protein lin kt vi tacrolinius l
TBS. Phc h Cyclosporin - Cyclophilin v tacrolimus - TBS f
cng mt i lc vi t bo ch cha phosphataz gi l Calxineurin v hot ng ca n ph thuc vo ion Ca"*. Calxineurin
nhn tn hiu thng tin th hai c sinh ra do nng Ca'*
tng ln sau khi c hot ha nh th th TCR s c tc dii
phn gii photphat (dephosphorylation) di vi yu l phin m
NP' - AT(- c mt tvong t bo cht. T d lm hot ha gen tn

205

h(.p IL 2 (hot ng ca NF - AT( cng phi hp vi yu L NF AT nm trong nhn). 1c dn^ ca )hc h thuc; khi lin kt
V('fi cc prolein ni bo (lr hiu s nh hng ti s hot ha t
ho T bing cch km hm hoi dng ca Calxineurin.

14.5. S dng cc xitokin v antixitokin

XiLokin l nhnf chl L ca l bo c tc dng vn nng n
ixiai don sm ca cd ch viin v to dng km hin min dch.
C 4 chin lc ch yii lm ni tc ng ca mt xitokin l:
bio vy s sn xut xitokin. ch bin xitokin ni bo d to ra
ml cing protein c hot tnh b km hm, trung ha xitokin
tron^ tun hon mu v km hm th th c hiu nhn bit xitokin.
Inielkin 1 l mt xitokin c lc dng trong giai on sm ca
vim v tn li 3 dng IL-la, IL-ip c hot tnh sinh hc) v
IL-1 ra (khng c hot tnh sinh hc). C hai loi th th nhn
bit IL-1 l IL-IRI v IL-lR II. Ngi ta iu ch mt s' khng
th chng li IL-1 v cc dng ha tan ca th th ca n e
trung ho s d tha qu ngng ca IL-1 trong tun hon mu.
Cc khng th chng li th th nhn bit IL-1 c s dng
cng vi IL-1 ra (dng ti t hp) s c tc dng bao vy s tip
nhn cc tn hiu trc khi vim qua trung gian tc ng ca ILI. IL-1 dng nh c vai tr ch yu trong cc qu trnh vim
t ong cn bnh thp khp. Cc th nghim bao vy tc ng ca
Ilv-1 trn m hnh ng vt c tc dng lm gim bnh vim
khp. Mt ng dng khc l km hm tc ng ca IL-ip lm
gim trng thi c tnh ca mt s bnh ung th mu. Ngi ta
chng minh c l IL-1 gy c vi cc t bo o nh p.
V vy vic bao vy tc ng ca IL-1 trong m hnh th nghim
(Vi vi ng vt b bnh tiu ng ph thuc insulin s lm
gim bt s tn cng ca cn bnh ny.
Intelkin 2 c vai tr quan trng trong hot ha cc lympho T.
Do , mt s' bnh lin quan n lympho T nh bnh t min s
thi b c quan cy ghp khng mong mun c nghin cu.
V d, cc t bo c tnh lympho T bc l qu mc cc th th
II.-2, nn c th tin rng lL-2 l yu t sinh trng ca t bo.
Tri li, vic s dng tng cng chc nng ca IL-2, cng lm
tnp cng p ng min dch chng li cc khi u.

206_______________________________________________________________ _

Trong mt vi nm gn y, ngi ta s dng cc khng

th chng li chui a ca th th IL-2 (CD 25) bao vy s hot
ha t bo T. Hin nay cng c mt s phng php th
nghim trn lm sng khai thc kha cnh min dch ny
bng cch s dng cc liu php c t min dch v min dch
phng x.
Khng th t chut chng li chui a ca th th IL-2 (khng
th anti CD 25) c th nghim iu tr s thi b mnh
ghp c qun thn. Mc d khng cn nghi ng g v hiu qu
ca vic th nghim ny nhng khng th anti CD 25 (cn gi l
khng th anti -Tac) cng l mt immunogen d gy p ng min
dch. Tuy nhin cc th nghim trn cng thc y vic iu
ch khng th lai ghp gen chng li CD 25 s khc phc c
kh khn trong iu tr lm sng.
Mt phng php mi to ra s hot ha IL-2 i vi cc t bo
gy hiu qu min dch cng c ng dng rng ri trong liu
php chhg khi u. Phng php ny ln u tin c Steven
Rosenberg M s dng. l vic tch cc t bo lytnpho t
mu ngoi vi ca bnh nhn b ung th, sau hot ha v nhn
ln in vitro cc t bo ny cng vi IL-2 qua mt s" ngy. Trong
nhng iu kin y, mt dng lympho khng phi T s c pht
trin c hnh thi lympho ht ln (LGL: Large Granular Lymphocytes). Trong cc m hnh th nghim ng vt, cc lympho
ny c c tnh rt cao chng li cc khi u thc nghim v c
th c gi l cc t bo git c hot ha bng lymphokin
(LAK: Lymphokine activated Killer). Liu php t bo LAK
c chng minh l lm thuyn gim mt phn hoc thuyn
gim hon ton trn 20% bnh nhn b mt s bnh ung th c
bit l ung th da c tnh (melanoma) v ung th biu m thn.
Tri vi liu php t bo LAK, ngi ta khng th iu tr trc
tip IL-2 bi v liu cao, IL-2 s gy c cho c th. Tuy vy,
tim IL-2 trc tip vo mch mu cng lm tng lng t bo
lympho, lm tng t bo git t nhin (NK) v lm tng hot
ng ca cc dng t bo kiu LAK. Hin nay M v Anh,
liu php trc tip v gin tip IL-2 cng bt u c s
dng cho mt s bnh ung th (c bit l hai bnh k trn), tuy
rng hiu qu ri ro gy cht khng mong mun c th t ti
4%.

207

Inteferon c xom nh mt thn h vin ca h m in dch

bim sin h c tc dng chng li viru s. Ni chung c hai kiu inteeron l intefcron v II. Inteoron I c hot tn h kh n g v iru s
bao gm hai loi l inLeeron a (IP^N - a) v inteeron p (IFN - P).
C: hai loi IFN - a v IFN - p ii c khi lng phn t xp x
18 k D a c lc dng chng l i s sin h sn t bo (an tip ro life ra tion), c bit l IFN - a, kch thch hot ng cc t bo git t
n hin (N K ) lm tng biu hin cc phn t H L A Idp I, nhng
khng lm tng bc l lp II. c bit, IFN - a l mt xitokin c
ng dng diu tr chng ung th c hiu qu. nht l ung ih
m u c tiih . Cc protein ti t hp bt ngun t gen IF N - a2 l
nhng sn phm thng m i, bao gm IF N -a v IF N - a2b,
C mt s c ch gii thch hot dng chng virus ca IFN - a
l; IF N -a km hm trc tip s tng hp cc protein ca viru s,
lm tng kh n n g nhn bit m in dch vi cc t bo b
nhim v iru s. B ng cch lm t.ng cng qu trn h bc l cc proUin ca HLA lp I (i vi IFN-a v P) v cc protein ca HLA
l) II (di vi
- a). Thm vo d. co IP^N a v p c tc dng
k cli tlich hot dng ca cc t bo mono, t bo dit t nhin, v
cc lynipho '1'. c bit IFN-a c cng nhn l thuc diu tr
ung th bch cii t bo tua (hairy cell leukaemia), mt dng
ung th lym pho B l)'t ihng. So vi cc t bo B b n h thng
cc t bo ung th 15 dng tua c s bc l cc th th IP^N-a
l n g ln t 4 n 8 ln, li u qui diu tr IF N - a i vi cc t
bo khi u l lm gim s ln. hdp ADX. gim tng hp protoin,
do lm thuyn gim hnh (> (a s cc bnh n h n v duy tr
hiu qui tr bnh t 1 n 2 nm.
IFN-a cng ic diu tr cho cc bnh nhn ung th biu ni
t bo thn, ung th a c tnh, bnh nliim v iru s vim gan B v
c m<n tnh (c th cha khi t 40 (ln 5()" s bnh nhn).
Inteferon-y l In tee ro n k iu II c sn xut t cc lym iho T
CD4 T ||1, T C D 8 v cc t bo N K. N hot ho cho s biu hin
ca cc phn t H L A lp II, lm thc y s bit ho cc l bo
niono thnh cc i thc bo. R i n " bin thn 1F X -( hoc k l h)
Vti yu t" hoi t ung Lh C rX F ; T iim o r necrosis actor) c tc
dng ph hu cc k sin h tr ii ni ho (nm bn trong i thc
bo) hoc kch thch t b o to r a cc dn xut oxy (HvOv, O c l.
0 1 , O B r ) v cc m o n o oxyt Iiit d p h h u t bo vi k h u n .

208______________________________________________________________

14.6. Liu php min dch t bo

Cc bch cu khc alen, cng loi (allogenic leucocytes) c th
c s dng iu tr cc bnh nhn gim bch cu, c bit
trng hp nhim trng mu. iu bt li ca phng php l
hiu qu c tnh cht tm thi v thi gian sng rt ngn ca
cc bch cu a nhn, hn na vic tim truyn c th gy ctn
ng tng hp khng th anti - HLA, ko theo s ph hu cc
bch cu v tiu cu c tim truyn.
Liu php t bo cng c s dng trong trng hp cy
ghp t bo ca bn thn (autograft) hoc cy ghp m khc alen
nhng cng loi (allograft). V d: Cy ghp tu xng, cy ghp
t bo ngun sinh mu cho tr s sinh thiu ht m in dch c
tnh.
Liu php t bo c chp nhn, ban u c th nghim
trn chut nht c m hnh bnh tiu ng typ I, hoc trn
chut b bnh vim khp. Ngi ta nhn thy cc t bo T
chut mc bnh c th truyn bnh cho chut lnh, dc x l
lm bt c tnh theo nguyn tc iu ch vacxin, sau c
tim truyn cho chut nh l mt vacxin. m hnh chut,
phng php ny cha khi bnh tiu ng cho chut,
ngi, vic th nghim lm sng liu php vacxin t bo hin
nay thu c nhng kt qu kh quan di vi cc bnh nhn
b bnh vim khp v cc bnh x cng nhiu dng m t bo.
Mt cng ngh mi cho php thc hin liu php min dch
tip nhn (truyn tnh min dch th ng t c th ny n c
th khc) l s dng s p ng min dch t bo lympho T
git cc virus nm bn trong t bo. Bnh nhn c cy ghp
tu xng khc a llen khc phc c s nh im C y to m e g a lo v ir u s
trong thi k b bnh gim bch cu, t cho php phc hi cc
t bo tu xng. Trong nhng nghin cu mi y, ngi ta thu
nhn cc t bo lympho T ca mu ngoi vi t c th cho tu
xng Irc khi cy ghj) v nui cy in v itro cng vi ngun
khng nguyn virus v IL-2. T s to c dng t bo gy
c (lympho Tp) v a vo bnh nhn tip nhn tu xng b
bnh gim bch cu. S p ng min dch cc t bo T chV
li virus mu ngoi vi sau thi k liu php ghp t bo T t
kt qu t"t v bnh nh<n c cha tr theo phng php trn
khng b nhim C ytom egalo iru s. Liu php ny c th tr thnli

209

mc trong nhng ph ng php cha bnh tng lai, bo v cho

cc bnh nhn ghp tu xng b thiu ht bch cu.

14.7. Liu php gen chng ung th

'>c ht, mun s dng liu php gen chng ung th, cc nh
khaa hc cn hiu r trong qu trnh pht sinh ung th, hin
tng p ng min dch chng ung th xy I'a nh th no?
c bng chng cho thy c hin tng p ng min dch chng
un th mu. Cc t bo ung th c th tham gia p ng min
(lch khi cc khng nguyn ung th c trnh din bi chnh cc
lhn t HLA trn b mt cc t bo khi u, hoc cng c th
ic trnh din bi cc t bo trnh din khng nguyn khc. Khi
(cc t bo b trd (T|il) c trnh din s tit ra cc IL-2, lm
huy ng cc t bo gy dc (T,) nhn bit t bo ung th v
])hn hu chng. Tham gia vo qu trnh p ng min dch ny,
Iig>i cc phn t HLA lp 1/ hoc l) II, cc cm bit ho CD4
(cua Tii), CD8 (ca T() cn c cc ng tn hiu (Co - signals) nh
CP28 v B7. Cc khi u ln t do pht tiin l do cc t bo c
t.rh trn thot khi s kim sot min dch. iu ny c th
x/ ra khi khng nguyn c hiu ung th khng c bc l
trn b mt t bo ung th, do mt di cc phn t HLA, hoc do
kh')ng c mt cc ng tn hiu tham gia trnh din khng nguyn,
(ln n hin tng mt ng (anergy) ca cc t bo Ti|.
S mt ng ca cc t bo T|| trong trnh din khng nguyn
l hin tng t bo T khng th nhn bit min dch v mt kh
nng p ng min drh.
liu php gen min dch nhm mc ch vt qua c ch tnm
thot min dch ca cc t bo ung th trnh by trn. C
th tm tt qu ti-nh tlic hin liu php gen chng ung th
nh sau: T' bo ung th, hoc khi u c ly ra ngi bnh,
dic nui cy v cc gen thch h(p c th c ci t vo cc t
b) con chu (hay hu du) ca chng. C th c 4 cch ci dt
pei nh sau;
a. t n g c n g k h n n g n h n bit m i n d ch , cn ci t cc
en m h o cho cc ph n t HLA.
b. Cc g e n n h n bit k h n g n guyn u n g t h c n g c ci t
"heo n iu c c h trn.

210

c. t n g cng hot ho cc lym p h o c hiu, cc g e n m hoa

cho s bc l cc n g tin h i u (ch n g h n B7) c n g c c h
ci t kh c p h c tinh tr n g m t ng ca t bo Tu.
d. Citi cng, n h m huy n g t n g cng t bo T g y c (T.),
ngi ta ci t gen m ho cho IL2.
Sau . cc t bo ci bin s c hon tr li cho bnh

nhn theo liu php quy nh.

Trn m hnh nghin cu ng vt, liu php gen chVig ung
th to ra nhng kt qu loi b tn gc cc khi u v bo v
chng bnh ti pht tr li. Liu php gen chng ung th ngi
c a vo lnh vc lm sng v ang ha hn mt tng
lai tt p nhm cha tr ung th mu v cc bnh ung th khc.

211

Chng XV. Min dch trong cy ghp

15.1. Khi nim v phn loi cy ghp

Thut ng cy ghp (transplantation) c s dng cho th
thut cy ghp mt m t bo hoc mt c quan ni tng (tng)
t mt c th cho thay th m hoc c quan ca c th nhn
b ph hu chc nng do bnh l hoc do chn thng vt l
nhm duy tr cuc sVig ca h. Ngi ta cng s dng thut ng
Graft ngha l ghp cho cc m t bo khng c cc ng n
mch mu nh ghp da, ghp gic mc... Ngi ta phn loi
thnh cc loi cy ghp ch yu sau y:
- C y g h p t th n : (A utograft hoc A u to lo g o u s tr a n s p la n t).
l kiu cy ghp cc m hoc c quan tng ca chnh bn thn
mt c th trong lm sng, vic cy ghp ny ph bin l cy
ghp da t v tr ny sang v tr khc. V d, cy ghp da ly t
phn khc ca c th ca mt bnh nhn b bng da mt.
Trong iu kin khng b nhim trng, s cy ghp t thn
lun lun cho kt qu tt ngha l khng c b hin tng thi
b mnh ghp.
- C y g h p c n g gen: ( S y n g r a ft hoc S yn g e n e ic tra n s p la n t) l
cy ghp m t bo hoc c quan tng gia nhng c th giVig
ht nhau v b gen di truyn. Trng hp ny c c gia hai
c th cho v nhn c sinh i cng trng (monozygotes) v
trong thc nghim lm sng him xy ra.
- C y g h p d gen: (A llograft) c thc h in gia c th cho v
c th nhn c b gen khc nhau nhng cng mt loi. y l
trng hp cy ghp ang c nghin cu v p dng ph
bin trong lm sng. Tuy nhin, cy ghp khc gen hay d gen
thng dn n kt qu thi b mnh ghp hoc c quan ghp.
- C g h p n g o i lai: (Xenograft) c thc hin gia cc loi
n g v t k h c nhau. y l trng hp cy gh p kh k h n

212

nht nhng cng ang c nghin cu d tig dng cho y h(

cha bnh.
Thnh cng ca cVy ghp ch yu ph thuc vo phn n^'
min dch ca c th nhn di vi khng nguyn cy ghp ca Cii
th cho, c mt c quan hoc mnh ghp. Trong rt nhiu
khtiR nguyn to nn tnh a hnh ca mt loi (cc allotypo)
ngi ta chng minh rng, tng th cc khng nguyn dic
m ho bi nhng gen ca phc h ph hp t chc ch y\i
(MHC) l quan trng nht i vi qu trnh cy ghp. Chng hn
trong thc t truyn mu. mt dng cy ghp m c bit, cc
khng nguyn ca h thng nhm mu ABO v Lewis c vai tr
rt quan trng. Mt tng th khc ca phc h ph hp t' chc
ph nh cc siu khng nguyn (superantigen: H Mls chut)
hoc cc khng nguyn c trnh din di dng peptit lin kl
vi cc phn t MHC ca c th cho hoc c th nhn, cng c
vai tr trong cy gh]).
Phn ng min dch ca c th nhn chVig li cc khn
nguyn ca mnh ghp d c thc hin bi cc t bo T v cc
khng th lm tn thng v gy ri lon chc nng sinh hc ca
mnh ghp. l cc phn ng thi b mnh ghp. Vic cy
ghp khc gen cng loi hay cy ghp khc loi u dn dn thii
b mnh ghp. Tu theo c ch min dch bnh l v cng (
phn ng thi b mnh ghp ngi ta c th chia ra mc thi
b ti cp, thi b cp thi b kinh nin hoc ko di.
Khi c th nhn khng c kh nng thi b mnh ghp d gon
do thiu ht min dch bnh l hoc do b km hm min dch v
nu mnh ghp hoc c quan tng c cha cc lympho T. th cc
lympho ny c th nhn bit khng nguyn ca c th nhn v
s gy ra p h n ng m n h g h p chng i v t ch, vit tt l Ci VH
(Graft Vorsus Host reaction).

15.2. Cc c ch thi b mnh ghp

tm hiu cc c ch thi b mnh ghp, cc m t bo hoc
c quan b thi b c phn tch sinh thit (biopsy). Ngi ta
thV r cc mnh ghp b thi b th hin s thm nhp gy
sng vim ca cc t bo bch cu n nhn, c th l cc t bo
lympho v cc i thc bo. Nh cc khng th n dng, ngi

213

lii c c l i n g m i n h S r m t c a cv l ho T C D 4. T C D 8, i th c
l)() l y m p h o B, t l)o ^it t nhiii NK. . c b n g c h n g cho
(liv c c cd cli ('him ii t h troii (lp n g s i n h l m i n dch

C'ng dc ]) dn^" rho hin tng thii b mnh ghp ging nh

toiig d p n g m i n clcli vn c. S c n b n g gia cc t h n h vin
cii;i li t h n g m i n (lch t b o v m i n dch dch t h c tc d n g
tli.i k h i n mc . (uy m v s hiu liin ca q u t r n h th i b
ma ih gh). XK1.v k i n
t h o b tr T C D 4 c h a m l l<n tip
xc V('ji k l i n g n^ai.vrn (nui la gi l T||0. l b o N g y t h ;
V'irj;in lioc n a i v e h(*l|)(>i cell) p pliiii m t d k h n g n g u v n (all'ia itgci) dc t r n h d in bi A F ( \ l b o T|O s b i t h o tr
t h n h Tjil lioc T||2. Khi Iroiig mi t r n g c IL-12 l s n p h m
li c a i t h c bo, cc T h o s bil h o I h n h T , | l - CD4*. B n
thui T || l cn> ( clic Iing h o t ho T- (UD8* c n g cc i th c
!j( t h n ^ (ua k h nn^' li(M IIj-2 v IFN-y ca n. T u y n h i n ,
Iiv I r o n ^ mi trin<( c h i m u ih l 1.-2 th cc t b o T||0 s
l)i h a t h n h {'c t bo T||2 v n h d cc IL4, ILIO s dc li t
l a l h o i h a cc t bo lym)lio 15 v siin x u t r a k h n g the.
l)i<)L(in v cc b n sa o A R N m cc m n h g h p
t r o i (u t r n h t h i b d cho t h y s c m t c a IL2. IFN-y
Iih n g khii lliy x u t hMi
iu c t h gdi vai tr c a
T|| l i u k h i n c h n g ti'nli th i b m n h gh p . Ngi t a biL
l FN-'/ c vai t r h u y (ng v h o t h o i t h c l)o. l m t n g
Ciivn,' q u t r n h ho l cc p h n t M H C cc m n h g h p , t o
i li( c h n g cic bil nliy cin di vi cc l y m p h o T g y dc T
('[ 8* c n g u n gc t c i h e n h n . IL2 c n g c vai t r h o t ho
<'( t b o T(-.
' m li. cc yu t x ilo k in c vai tr d c h i u t h a m gia v o q u
t r i h d i u h o s i h i 1)0 C'u; m n h gli). T u y n h i n , ngi t a c n
r c c h n h n d n g cc d k h n g n g u y n cc m n h g h p
s d i n r a n h t h no? T r o n g diu k i n c y g h p t h c n g h i m

cig nh cy ghp lun sn c ihc hin gia cc c th

k h')ag c q u a n h g n gi v gon c a c n g m t loi, cc k h n g
n g j y n dc gi l d k h n g n g u y n q u a n t r n g s c m ho
Ixi m t p h c h g e n c a M H C (lioc H L A c a ngi). C h c n n g
si r h l c a cc M H C l t r n h din k h n g n g u y n cho cc t b o
T. V n q u a n t r n g l cc d k h n g n g u y n c n h n b i t n h
t h i n o ? Ngi t a MU r a h a i k h n n g n h n b i t :

2M

- T h n h t: h m i n d c h ca c t h n h n b it m t M H C n g u y i
vn v coi l m t s nh n bit trc tip d k h n g ngu yn.
- Th hai: m t p e p tit ht ngun t M H C l (ca c th cho cK
c coi l a llo p e p tit) c t h c trin h d i n tr o n g m t rn h
ca p h c h M H C ca c t h nhn. l s n h n b it g ia n
tip d k h n g nguyn. N gi ta bit r cc t bo c th
n h n bit m t s ling cc p h n t M H C c a c th cho viit
tri hn s lng cc a llo p e p tit c ch' b in (t 1 0 0 0 n
10000). D o , cc d k h n g ngu yn c n h n b i t hi h
th n g m in d ch ca c th n h n kh n g c h bao g m cc p h n
t M H C ca c t h cho m cn g m c cc p h n t M H C chiia
n g cc a llo p e p tit c s n tro n g M H C c a c t h cho. C hinh
n h cc p h n t M H C ca c th cho m ang sn allopeptit {'

cu trc bn vng cng c kh nng kch thch s nhn bit (l

khng nguyn ca c th nhn.

15.3. Phn loi cc phn ng thi b mnh ghp

Trong thc hnh lm sng c rt nhiu c quan tng dc cy
ghp v phn ln u kiu ghp d gen. Do ngi ta lun
lun phi x l cc loi thuc km hm min dch v diu hin
min dch. S thi b mnh ghp c th dc phn loi tv thoo
quy m thi gian xu't hin c ch thi b. Sau y l bng trnh
by s phn loi ca cc phn ng thi b m nh ghp.
Bng 15.1. Phn loi s thi b m nh ghp

Kiu thi ghp

Thi b ti cp

Thi gian cy
ghp

C ch m in dich c thc
xy ra

Din ra theo pht

Cc k h n g th mi

h n h t h n h
Thi b r t cp

T 1 n 5 ngy

Cc lympho T

Thi b cp tnh

T tuaii th 2

Cc lympho T

T nhiu th n g

Cc k h n g th. b ih v

n hng nm

cc ph n t bm dnh

Thi

(trng din)

ko

di

215

S thi b ti cp din ra Irong cc trng hp cy ghp khng

cng nhm mu, dc bit l khc nhm mu ABO. Ngi ra cn
bit r cc khng nguyn nhm mu ABO khng ch c mt trn
b mt t bo hng cu m cn c cc t bo biu m. Cc
khng th ca c th nhn cng tham gia chng li trc tip cc
phn t HLA lp I ca c th cho.
Trong thi b cp tnh cc lympho T ca c th nhn trc tip
nhn dng cc alloantigen theo c ch nhn dng trc tip.
S thi b ko di hay trng din xy ra sau khi c s cy
ghp thnh cng. Nguyn nhn ca qu trnh thi b ny vn
cn cha c bit r v bnh l. Ngi ta cho rng c qu trnh
tn thng cc ni m mao mch, c th do mt yu t no
dn n bin chng sau ny. Ni m c th b ph hu do phc
h khng th khng nguyn ngoi lai c tch lu dn cc m
da n s hot ho b th. Cc xitokin nh IL 1, IL 6, TNF-y v
cc phn t bm dnh cng c xu't hin trong qu trnh thi
b, c tc dng iu ho mc hot ng ca cc t' bo ni m.

15.4. Mt s c im lm sng trong cy ghp

15.4.1. C th cho mnh ghp hoc c quan

I vi vic ghp thn, ghp tu xng v c bit l ghp cc
thy gan, cc nh phu thut yu cu c th cho trng thi
ang sng v c s chp nhn t nguyn. i vi cc loi cy
ghp khc, nu c th cho trng thi cht no (hn m xy
ra) th vic hi sinh (resanimation) i vi c th cho: tr gip
kling kh h hp. duy tr huyt p hiu qu s ng vai tr quan
trng trong kt qu cy ghp sau ny.
Mi c th cn c kim tra v nhm mu khng nguyn
Rhesus (Rh), phc h HLA-A, HLA-B, HLA-DR cng nh kh
nng truyn nhim cc bnh virus nh vim gan siu trng,
thiu ht m in dch HIV.,.. Vic nghin cu khng th chng li
C v to m e g a lo v ir u s (CMV; C y to m eg a lo v iru s thng nhim vo tu
xing hoc c quan ghp) l iu rt quan trng, phng ri ro
d xy n cho cc c th nhn.

216

15.4.2. C th nhn mnh ghp

Cc quy lut la chn ngi nhn phi lun lun tho mn
min dch nh phc h HLA. Cc mnh ghp c quan lun lun
cn c s ph hp khng nguyn nhm mu ABO. Ngi ta lun
tn trng s ging nhau v nhm mu trnh s tch lu qu
nhiu cc tng c nhm mu 0 trong s" cc c th nhn
ang i ghp. Trc khi cy ghp ngi ta cng xt nghim cc
phn ng cho bch cu (Cross - Match). l phn ng tm s
ph hp trc tip nhm pht hin cc d khng th (alloantibody) chng li hng cu hoc chng li cc bch cu gia hai c
th cho v nhn. Phdng php ny c trnh by bng 15.2.

Bng 15.2. Minh ho phn ng Cross - Match bch cu

Cc thnh phn

Lympho T ngi cho

Huyt thanh ngi nhn

Ab*

Ab

Ab*

Ab-

Huyt thanh th (b th

thm

khng

khng

khng

Kim tra

v khng th)
Cht mu (eosin Y)

mu
Phn ng Cross - Match

Phn ng Cross - Match dng tnh l mt chng ch nh cho

trng hp ghp thn, ch r s c mt ca khng th ca ngi

nhn chng li khng nguyn MHC lp I ca ngi cho.

15.5. Liu php km hm min dch trong cy ghp

Ngy nay cc quy trnh x l cht km hm min dch ngy a
dng v thch ng vi cc ri ro trong thi b mnh ghp hoc
tu theo kiu c quan c cy ghp, tu thuc vo tnh phn
ng ca tng c th nhn. Ngi ta s dng rt nhiu cht
km hm m in dch tm kim s hip ng trong cy ghp
(synergy) v lm ^ m thp s ri ro ca cc hiu qu ph khng
mong mun. Tt c qu trnh cy ghp c gim st lm sng

217

v gim st sinh hc rt u n nhanh chng pht hin cc

khng hong ca s thi b mnh ghp. Khi s dng cc cht
km hm min dch ngi ta cng lun lun theo di kh nng b
nhim trng c hi thng hay i km, c bit l nhim cyto m e g a lo viru s v nhiu loi virus gy bnh khc. Bn cnh
cc ri ro v ung th thng hay tng ln trong qu trnh cy
ghp thng c theo di v phng.
Mt s dng thuc km hm min dch c th c gii thiu
sau y:
A z a th io p r in \ thuic ny chng Irao i cht, tc ng nh l
chtt i khng pui'in, c chc nng ging nh tc nhn chng
tng sin h t bo. Thuc c s d n g trn hai th p k i vi

llgli.
C orticosteroid: c nhiu tc dng ln h min dch nh lm

giam s lng cc t bo ljmi)ho B tun hon, km hm s qua

li ca cc t bo mono, km hm s tng sinh v bc l cc gen
xitokin ca t bo T (cc ILl, IL2, IL6. INF-y v TNF-a). nh
liting ph ca thuc cng biu hin da, xng v nhng m t
lio khc.
P re d n izo n : dc s dng tc thi trc hoc ngay trong lc cy
Khp vi liu lng gim dn. Methylprednizolon c iu tr
ngay khi chn on l c hin tng thii b mnh ghp v s
(lng hng ngy ko di lin tip trong 3 ngy.
Mt s thut' km hm min dch khc cng c s dng ph
biMi l; Cyclrisporin A. Tacrolimus, Sirolimus. Sau y trnh by
tm tt mt s cr ch tc diig ca thub.
B n g 1 5 .3 . C c h l c ii' c a Ih u o k m h m m i n d c h

Tlui<-

Kiu t c (in^

A/athiopnn

K i

(\> rt ic o s lc T o h l

i a o

( ' \ 1(IS|)U)'1?1

l;n> V;'iy coi dn hoi lio t' hiM) '' p h ihu()c on

liAii

v y

un^"

])( l

l)

)u ri

c(*

x i t o k i n

'Pivcrulinius

Bao

S r o l i n i u s

Hao vAy s tiiK siil) t Imo (lo L-2 kch t h r h v bau vy c r tn

v y c o n d c'n h o t

h o n l

l)<) T

) h t h u r i o n ('"*

}u(}u i!n^ k ch th c h (UI tru n ^ a i (''TLA-4

218

M t s k h n g t h dn d n g v a (lng; l th u c k m h m m i n

dch cng c s dng chnt li s bc l phn t b

m t

c a o c t b o l y m ) h o T n h T('l)4". TCD8* h o c t c n g v f )
cc t h t h IL 2 ( C 25).

15.6. Mang thai l trng thi t nhin ca cy ghp d

gen
T h a i ( t h a i n h i v cc p h n ph ) l m t d n g m c g e n bc l
cc p h n t M H C dc m ho bi m t k iu n bi (h;i[)!otvpe) c a ngi cha, n h n g s p h t t r i n c a n kh n f b igi 1
c n t r o n g th i g i a n m a n g t h a i c a c th m. mcc d v n c si
t h i u h t m i n dch. Cc c h ca nghch l min dch n y cho (li 1
nay v n c h a s n g t.
N h a u t h a i do t o t h n h t cc t bo nui ( c y l o t r o p h o b l a s t e )

v hp bo nui (syncyliotrojhoblaste) ti) xc trc tip vi liii

h o n m u c a ngi m. T r o n g thdi g i a n m a n g t h a i , cc Iih n t i i

IgG c a ngi m c n g dc d m b o v n c h u y n v o h t u n
h o n c a phi d m bo chc n n g m i n dch b a n d u c tn l 1
c h t v a y mn c a th a i. Cc t b o n h a u c n g bc l co klini:^

nguyn HLA lp I (A, B, c v G) nhng c ch(! ph l)iK mL

dnf g lycopro loin l s i a lo m u x i n . Cc t bo lyiTi)ho c a m d
d n g v t q u a l u n lion m u c a i h a i tho o m t (<i c h i hii i
s n g t n h n g r t (' h iu q u cho p h p t r n h c hiii Unp
GVH. C c t b o hnt c u ( a tliai c n g c t h c h u y n s a n g m u
m t r o n g giai o n cui c a ihi k m a n g th ai. C c t b o n u i
v c t h c cc t b o l y m p h o c a t h a i c n g c h u y n s a n g t i i n
h o n m u m nfay t r o n g 3 t h n g d u ti n v g y r a s n x n l f(C'
k h n g t h c h n g li l L A (Idp I v lp II). K h n g Lh chiit l i
HL A c a Lhai dc p li t h i n 10% c a ngi m a n g t h a i lii dv-i
v 30% c a ngi m a n g t h a i ln t h ba. T u y n h i n , n h n g k h n g
th c a ngi m t h c t b h:Yp t h t r n t bo MUi v khtiy:
gy b t k m t n h h n g n o ti t h a i nhi.
S ln ln c a t b o nui c i u h o b n g cc x i to k i n d(C
k ch t h c h b n g cc I L 3 v y u t G M - C S F . Cc t h n g h i m l i
c h u t cho t h y IFN-y v T N F - a c t c d n g k m h m s i n h Irin:
t b o n u i g y r a hiii tiiig xy t h a i. Cc h o c m o n c a Iihai.i
t h a i c t c d n g (iu b in p n g m i n dch c a c t h m troiii
khong vi mi t r n g vng ti p xc s i a m v tliai n hi. Kh i

219

d. s lng cc th th tip nhn hocmon progesteron ca cc t

bo lympho ca m gim xung mnh m. Trong khi hot
ng NK ca cc t bo mng rng ca d con tng ln lc ban
u th thai, sau d gim xung khi c thai v tng ln mnh
khi ngi m lao dng.
Vic nghin cu cc hin tng min dch trong khi c thai v
mi quan h min dch gia thai nhi v ngi m s gip cho vic
sa cha mt s bnh bm sinh (tim khng th d phng chng
Rh*(D) chng xy thai) hoc mt s bnh ung th nhau, ng c
thai nghn...

221

I. Cu hi n tp min dch c s

Chng I
1. V s mi quan h gia min dch t nhin (min dch bm
sinh) v min dch tip thu (min dch c hiu hoc thch
ng). T nu r thnh phn t bo a nhn, c tnh ca t
bo NK, thnh phn cc i thc bo v cc thnh phn min
dch th dch (b th, xintokin, khng th).
2. Thnh phn v c tnh ca cc t bo lympho T v t bo
lympho B.
3. V sd bit ho v v tr bit ho ca t bo lympho T.
4. V s bit ho v v tr bit ho ca t bo lympho B.
5. Thnh phn v chc nng ca cc Xitokin.
6. Trnh by tm tt l thuyt la chn dng trong min dch v
v s km theo gii thch.
7. Nguyn tc c bn trong liu php tim chng vacxin. Cho v
d v cc dng vacxin c s dng hin nay.

Chng II
1. nh ngha v khng nguyn.
2. Gii thch r tnh khng nguyn (antigenecity) v tnh min
dch ca khng nguyn (immunologenecity). Khi gy min dch
cho ng vt nhn khng th, khng nguyn s dng cn c
nhng c im no?
3. T h no l mt hapten?
4. Nu c tnh sinh min dch ca mt s dng khng nguyn.

Chng III
1. V s mt phn t khng th v cho bit c im c a
chui nng, chui nh ca phn t khng th. Ch r v tr ca
Fab (mnh khng th kt vi khng nguyn). F(ab>2, Fc (mnh
peptit d kt tinh ca khng th. S lng cc cu lin kit
disunfua ca khng th IgG.
2. Phn loi cc khng th v chc nng ca tng loi khng th.
3. C s di truyn v tnh a dng ca khng th.
4. Thnh phn phn t, h gen v cc chc nng ca cc th th
lympho B (BCR).
5. Thnh phn phn t v cc chc nng ca cc th th lym pho
T (TCR).
6. Nguyn tc v s sn xut khng th n dng (monoclonal
antibody) v khng th ti t hp.

Chng IV
1. V s v cu trc phn t HLA - lp I v HLA - lp II v S(0
snh s khc nhau v cu trc v chc nng?
2. V s v s nh khu ca cc gen m ha cho cc phn tiii
HLA - I. HLA - II v nu mt s c im chnh ca cc ph(C
h gen ny.

Chng V
1. Cc t h n h p h n p r o t e i n c a b th.

2. V s d con ng hot ho b th theo c ch c in (c ch

c hiu). Nu r cc b th tham gia v cc yu t" iu h o
con ng ny. So snh vi con ng hot ho b th c lectim
MB tham gia vi con ng c in.
3. V s con dng hot ho b th theo c ch bn cnh (c
ch^ khng c hiu). Nu r cc b th tham gia v cc yu t('
iu ho.
4. Hiu qu sinh hc ca hot ho b th l g? V s km the <0
hiu qu tn cng ph v m ngt bo vi khun v t bo clh
c hai.

223

5. Nu m quan h gia ba con ng hot ho b th.

6. Cc bnh l pht sinh do thiu ht bm sinh cc loi b th.

Chng VI
1. Nu c tnh chung ca phn ng khng nguyn - khng th?
2. c im nguyn tc ca phng php khuch tn min dch
Ouchterlony?
3. Nguyn tc v c im ca k thut ELISA.

Chng VII
1. Thnh phn cc c quan min dch s cp (c quan lympho
trung ng) v vai tr sinh hc ca chng.
2. Thnh phn cc c quan min dch th cp (hay ngoi vi) v
chc nng sinh hc ca chng.
3. Thnh phn cc t bo trnh din khng nguyn (APC).

Chng VIII
1. Trnh by qu trnh hp tc gia cc i thc bo v cc lympho T.
2. V s s trnh din khng nguyn cho cc dng t bo T.
Nu r c tnh hiu qu ca cc cm bit ho khng nguyn
CD4 v CD8.
3. Nu s hp tc gia lympho T b tr (Th) v lympho B v hiu
qu sinh hc.
4. So snh hai dng iu ho min dch bng cc lympho T c ch
c hiu v khng c hiu.
5. Nu r c ch iu ho p ng min dch bng c ch mng
li Idiotip.
6. Vai tr ca h thn kinh v ni tit trong iu ho p ng
min dich.

224

Chng IX v chng X
1. C ch min dch ca hin tng qu mn phn v c s tham
gia ca IgE.
2. C ch min dch v hu qu ca qu mn c s tham gia ca
IgM v IgG.
3. Nu hai loi bnh qu mn kiu II: bnh tan hng cu v
ngng kt hng cu do truyn mu v do khng ph hp
khng nguyn Rhesus.
4. Nu tm tt cc c ch min dch chng li s xm nhp ca vi
khun (vi khun, vi nm) v k sinh trng.
5. Quan im hin i v ung th.
6. Nu cc kiu t bo v cc yu t" th dch p ng chng li
ung th.

7. Hi chng ung th ca dng t bo Lyiipho B: bnh u tu. uiig

th bch cu, Bnh u lympho (lymphoma).
8. Hi chng u dng t bo lympho T.
9. Nguyn nhn t bin gen v t bin nhim sc th ca c c
loi bnh ung th. c im lm sng ca mt s bnh uiig
th. Mt s" ch th ung th,ng dng trong chn on v theo
di bnh.
10.Liu php min dch khng th chng ung th.
11.Trnh by liu php gen chng ung th.
12.Trnh by liu php s dng Xitokin chng ung th.
IS.Trnh by liu php min dch t bo chng ung th.

Chng XI
1.Cc biu hin bnh thiu ht min dch (nguyn thu dng
lympho B do nhim trng ti din).
2.
Trnh by biu hin thiu ht min dch nguyn thu dng
lympho T do yu t' di truyn.
3. Trnh by cc con ng ly lan bnh thiu ht min dch mc
phi do HIV.
4. Trnh by cu trc ca virus HIV.
5. Nu cc giai on tin trin bnh l do nhim HIV ngi.
6. V sao khi nhim HIV, h min dch ca ngi b suy gim,
khng phng cu cha?

225

Chng XII
nh ngha dung np min dch l g?
1. Trnh by cc c ch c th gii thch hin tng dung np
min dch.
2. nh ngha v cc bnh t min, cho mt vi v d v bnh t
min.
3. Trnh by cc nguyn nhn gy bnh t min.
4. Nu mt s' phng hng iu tr cc bnh t min.

Chng XIII
1. c im h min dch ca lp c xng.
2. c im h min dch ca lp ng vt bin nhit.

3. c im h min dch ca lp chim.

4. c im h min dch t bo ca b linh trng (loi kh).
5. c im cc loi khng th v b th ca mt s loi kh.
6. So snh phc h ph hp vi t chc ch yu ca mt s linh
trng RhLA, CiLA, HLA.

Chng XIV
1. Nguyn tc min dch hc ca liu php cha bnh bng tim
chng (vaccination).
2. Nguyn tc chung ca sn xut vacxin.
3. Cc dng vacxin c sn xut hin nay trn th gii v Vit
Nam
4. C th sn xut vacxin cha bnh cho cc loi ng vt (gia
cm, thu cm) no c hiu qu tt nht? V sao?

Chng XV
1. C ch thi b cc mhh ghp.
2. Nu mt "s c im lm sng ch yu trong cy ghp.
3. V sao ni mang thai l trng thi t nhin ca cy ghp d
gen (alograft).

226

II. Mt s dng cu hi thi min dch

Cu 1: Cho bit cc trng hp

A = IgG
B = IgM
c = C hai loi trn
D = Khng c loi no c
Hy ch chn mt ch ci cho p n ng ca cc cu hi sau:
1. C cha chui X. v lin kt i sulfit (S-S).
2. C cha chui a.
3. C cha chui e.
4. i qua mng nhau thai.
5. C cha chui n (J).
6. C cha chui mnh tit s.
Cu 2: Cho bit cc trng hp
A = IgG
B = IgM
C = IgD
D = IgE
Hy chn ch mt ch ci cho p n ng ca cc cu hi sau :
1. Lp khng th quan trng trong bo v min dch, thng c
mt tuyn nhy ng h hp, ng tit liu tinh dc.
2. Lp khng th chim t l cao nht trong huyt thanh ngi
trng thnh.
3. Lp khng th c vai tr quan trng trong d ng typ I.
4. Lp khng th xut hin u tin trong tin ho v p ng
min dch s cp.
5. Lp khng th c thi gian bn hu di nh^t.
6. Lp khng th t bit r chc nng nhng lun c mt trn
mng t bo B chn v khng c trn mng t bo B ghi
nh.
Cu 3: Cho bit cc trng hp
A = C3b
B = C4b
c = Cho c hai loi trn
D = Khng c loi no c

227
H y c h n c h i m t c h ci cho p n n g c a cc c u h i sau:
1. T h a m g ia v o con n g h o t h o c i n .

2. C lin kt vi ion canxi (Ca'"^) trong qu trnh hot ho.

3. Tham gia vo con ng hot ho bn cnh.
4. C kh nng to ra hot ng ca anaphylatoxin.
5. Phc h b th CiQrs s b phn li l do:
A: C s tham gia ca Cl-inh.
B: B mt ion Canxi v c s tham gia ca Cl-inh.
C: B mt ion Magie.
D: c ba loi trn.
C u 4 : Cho cc trng hp ch ci sau v dng n la chn

cho cc cu hi di:
A = 1 , 2 v 3 l n g

c = 2 v 4 l ng

B = 1 v 3 l n g

D
= 4 l ng
E = Tt c l ng
a) Hy chn p n ng nht cho cc cu hi:
1. Cho bit c quan lympho trung ng?
2. Cho bit c quan lympho ngoi vi (a phng)?
- Tu xng (Bone marrovv).
- Lch (Spleen).
- Tuyn c (Thymus).
- Hch bch huyt (Lymphonodes).
b) Hy chn p n ng nht cho cu hi:
Nhng t bo min dch sau y loi no tham gia vo h t bo
min dch?
1. Bch cu c ht.
2. Te bo lym pho.
3. T bo mono.
4. i thc bo.
c) Hy chn p n ng nht cho cu hi:
Cc t bo ngun a nng c siiih ra t c quan (hoc cc c
quan no)?
1. Gan phi.
2. Ti non hong.
3. Tu xng ca ngi trng thnh.
4. Lch ca ngi trng thnh.

228

d) H y ch n p n n g n h t cho cu hi:

Cc t bo lympho B ca ngi v chim c gio dng v

trng thnh t cc c quan no?
1. Ti Pabricius hoc vng tng ng tu xng ca ng vt
bc cao.
2. Hch bch huyt.
3. Tu xng.

4. Lch.

Cu 5: Hy chn ch mt ch ci cho p n ng cc trng

h p s a u ;

A = IgCi

B = IgM

c = C hai loi gG v IgM

D = Khng c loi no c
1. Khng th no c cha chui 8.
2. Khng th no c cha chui .
3. Khng th no c cha chui K.
4. Khng th no c cha chui J.
5. Khng th no c cha mnh tit s.
6. Khng th no i qua mng nhau thai.
7. Cc khng th no c nhng c tnh sau:
- C cha cc chui n<ng ging nhau.
- C cha cc chui nh ging nhau.
- C cha gc ng saccacharide.
- Di ng trong in trng ging nhau.
Cu 6; Cho cc trng hp sau:
A : Vng bin i ca chui nng.
B ; Vng khng bin i ca chui nng,
c : C hai trng hp trn.
D : Khng c trng hp no.
H y ch n c h ci cho p n n g i vi g e n n o m h a cho
cc v n g c a p h n t k h n g th:

1. Gen J.

2. Gen D.
8 . G en L.

4. G('11 m ho vng c ca mnh Fc.

5. Cc gen exon m ho cho cc domain VH l.
6. Cc gen pxon m ho cho cc domain VH3 v VH4 ca IgM.
7. Cc gen intron ca cc Ig.

229
C u 7 : C h o c c tr n g h p:

A :T -C D 4 ^
C: C hai loi trn

B tT b o B
D: K hng c loi no

1. Lin kt vi t bo trnh din khng nguyn (APC) cha MHC

l p l.

2. Lin kt vi t bo trnh din khng nguyn (APC) cha MHC

lp II.
3 . T b o n o ti 't r a c c k h n g t h .
4 . T b o n o t i t r a I L l .
5 . T b o n o t i t r a y u t s in h t r n g B C G F .

6. T bo no sn xu't ra IFN-y.
C u 8 : Cho cc trng hp sau . hy chn m t ch ci;
A: CD4*

B: CD8*

C; C hai loi trn

D: K hng c loi no.

1. L o i t b o n o t h a m g i a v o q u t r n h t i p n h n s t r n h d i n
khng nguyn.

2. Loi t bo no tham gia vo qu trn h tip n h n s trn h din

k h n g n g u y n n i s in h .

3. Loi t bo no tham gia vo qu trn h tip n h n s trnh din

k h n g n g u y n n g o i s in h .

4. Loi t bo gy c Tc c cha cm b it ho k h n g n gu yn CD
no.

5. Loi t bo no c vai tr quan trng trong n h im khi p h t

virus HIV-1.
C u 9 ; So sn h cu trc phn t. chc n n g m in dch v h
gen oa ph c h H L A .

CulO ; C cli t bo hc v phn t ca s trnh din khn.u

nguyn.

C u l l : C hng m inh s a dn g ca k h n g th b n g C(f c h (li

t r u y n v t i t h p g e n .

C u 12 : c d ch t bo hc v phn t ca s trnh din khi

Iig u y n .
C u

1 3 : N u n g d n g c a c c x it o k in (c y t o k in e e ) t r o n g c h a

bnli tru yn nh im v bnh un g th.

C u 14 ; N u ng d ng k h n g th t i t hp tron g cha bnh.
C u 15 : P hii tch cc c c h th i b m anh ghp.
C u 1 6 : V sao trong cy ghp t n g (m t bo hoc c qua l)
cn phi s d ng liu php km htn m in dch.

231

PH LC

233

Ph ic I. c im cu trc v chc nng ca

cc khng nguyn CD

K h n g
ng u y n
cb

B iu h in (c
b o

T r n g
lng
p h n t
(k D a)

C c ch c n n g

CDl
a,b,c,d

Cc t' bo
luyn c v,
cc t bo
Langerhan,
cc t bo
lua. t bo B
(C D lc), biu
m rut, c
trn,
m ch
m u (C D ld )
C c t bo T,
cc t bo
luvn c, cc
t 'b o NK

43 - 49

Phn t ging
M HC lp I. kt
hp
vi
p2microglobulin.
C
\ai
tr
chuyn
ho
trong vic trnh

C c t bo
tuyn c, cc
t bo T

y: 2528
<S:20
e:20

CD2

CD3

d i n

cc

Cc tp hp
con t bo
tuyn c. Cc
t bo T:TH1

Imm unoglobulin

khng

nguyn cht bo
45 -58

Phn t dnh
bm, liCn kt vi
CD58 (LFA-3).
Lin kt vi Lck
ni bo v hot
ho t bo T
Kt hp vi th
th
khng
nguyn t bo T
(TCR). Cn thit
cho biu hin b
m t t b o

CD4

C c tn M i q u a n
khc
h h h n g

55

T ll,
LFA -2

T3

Immu-

noglobulin

Inimiinoglobulin

truyn tn hiu
nhT C R ,
ng th th 4 . L3T4 Immiic h o c c p h n t

M HC lp II.
Lin kt vi Lck

n o g lo b u lin

234

CD5

CD6

CD7

v
TH 2
(khong 2/3
cc t bo T
ngoi
vi),
bch cu om
nhn,
i
thc bo.
Cc t bo
67
tuyn c, cc
t bo T, tp
hp con cc
t bo B
Cc t bo 1 0 0 -1 3 0
tuyn c, cc
t bo T, cc
t bo B
bnh
bch
cu m n tnh
Cc t bo
40
to m u a
nng, cc t
bo tuyn c,
cc t bo T

trn b m t t
bo cht mng.
Thu
th
cho
g p 2 0 HIV-1 v
HIV-2.

ri,L y l

Lin
kt
CD166

vi r i

Cha r, dom ain

t bo cht lin
kt vi PI 3
kinaza bng lin
kt cho.
L
du hiu cho
bnh bch cu
cp tnh t bo T
v bnh bch
cu
t
bo
ngun a nng
ng th th T8,
cho cc phn t Lyt2.3
MHC lp I. Lin
kt vi Lck trn
b mt mng t

Th
thu
(n
thi)

th
dn
xc

Th
thu
(n
thi)

th
dn
xc

Im m u-

noglobulin

CD8

CD9

Cc tp hp a ;3 2 -3 4
con t bo p:32-34
tuyn c, cc
t bo T gy
c t bo
(khong 1/3
cc t bo T
ngoi vi)
Tin t bo
24
B,

cc

bch

cu
dn
nhn, t bo
ua axit, bch
cu a kim.

ImmU'
noglobulin

bo clt
Lm trung gian
cho s kt t
tiu cu v hot
ho
nh
PcyRIIa, c th
ng
vai
tr

Protein
vt
qua
m ng
4
ln. cng
c gi
l protein

235
tiu cu, CiC
t bo T hot
ho, no v
cc t bo
thn
kinh
ngoi
bin,
c irn c
rnch.
Tin thn t
bo B v T,
cc t bo
tu
m
xng.

trong s dch
chuyn t bo.

xuyn
mng
(TM4)

100

Proteinaza kim Endopep

loi km. L du idaza
hiu cho bnh
bch cu cp
tnh tin t bo
B (ALL)
bch cu
cp tnh
ph bin
CALLA

CDI la Cc t bo
lympho, bch
cu ht, cc
bch cu n
nhn v di
thc bo

180

C D llb Cc t bo
dng tuv v
t b a o N K

170

C D llc Cc t' bo
dng tu

150

Di n v a L
ca
integrin
LFA-1 (kt hp
vi CD18); lin
kl vi CD54
(ICAM-1),
CD102 (ICAM2), v CD50
(ICAM-3)
Di n v a M
ca
integrin
CR3 (kt hp
vi CD18): iin
kt vi CD54,
thnh phn b
th iC3b, v cc
protein
trong
cht nn ngoi
bo
Di n v aX
ca integrin CR4
(kt
hp
vi
CD18): lin kt
vi fibrinogen.

'c D lO

LFA-1

Integrin a

Mac-1

Integrin a
(cht kt
dnh
t
bo)

CR4,
p 150, 95

Integrin a

236

C D lld

Bch cu

125

CDw l2 Bch cu n
nhn,
bch
cu ht, liu
cu
CD13

CD14

Cc
bch
nhn
Cc
bch
nhn

t
cu
tu
t
cu
tu

90-120

Di cm v a D
ca integrin, kt
hp vi CD18;
lin
kt
vi
CD50
Cha r

bo 150-170 Proteinaza
cm
loai km
bo
ii

CD15

Bch
cu
trung
tnh,
bch cu a
axit,
bch
cu n nhn

CD15S

Bch cu, t
bo ni m

53-55

kim Aminopeptidaz N

Th th cho
phc
h
lipopolysacarit
v protein lin
kt lipopolysacarit (LBP)
Trisacarit
ln ^ewis
cng c biu (Le')
hin trn cc
glycolipit
v
nhiu glycoprotein b mt t
bo
Ligand (cu t Sialylgn)
cho '^v v is'

CD62E, p
CD15U

In t e g r in a

(sLe)

CD15 sunphat

Poly-Na c e t y l-

lactsa*
min
Cc cu
trc
cacbohy-

drat
CD16

Bch
trung
cc t
NK, i
bo

cu
tnh,
bo
thc

50-80

Thnh phn ca PcyRIII

th th Fc i lc
thp,
PcyRll,
lm ung gian
cho s thc bo
v tnh gy c t
b do t bo ph
thuc khng th.

Itimunoglobulin

237
CDvvl? Bch
cu
trung
tnh,
bch cu dn
nhn.
tiu
cu
CD18
Bch cu

Lactosyl
cera
mide, mt gly
cosphingolipid
b mt t bo
95

CD19

Cc t' bo B

95

CD20

Cc t bo B

33-37

CD21

Cc t' bo B
trng thnh,
cc t bo
tua nang

145

CD22

a c t bo B
trng thnh

a :i 3 0
p: 140

Di n v inIntegrin p
tegrin P2, kt
hp vi CDl la,
b,c v d
mmu'lo ihiih phc
noglobuhp vi C D 21
(CR2) v CD8i
lin
(TAPA -I). ng
th th cho cc
l bo B- domain nm trong
t bo cht lin
kt vi tyrozin
kinaza v P13kinaza t bo
cht.
Cc
oligomer
Cha
4
on proCD20 c th to
tein
thnh mt knh
xuyn
ion
c th
mng
dng vai tr
trong iu ho
qu trnh hot
ho t bo B
Protcin
Th th i vi CR2
iu
cc thnh phn
khin b
b th C3d, virul
th (CCP)
Epstein
-I;irr.
Cng vi C D I9
v CD81, CD21
to ng th th
di VI cc t
boB
Lin k vi Sia BL-CAM Immunoglobuloconjugate
lin

238

cn23
I

Cc l bo B
trng thnh,
cc i thc
bo liol ho.
bch cu ira
axit. cc (
bo tua nang,
cc tiu cu
CYic t bo B,
cc bch ciu
ht

11
1!
i
1
CD24

45

35-45

CD23

CD26

CD27

CD28

Cc t bo J
hot ho, Cik
t' bo B v
cc bch cu
n nhn
Cc t bo B
v T hot
ho; cc di
thc bo
Cc t bo
tuyn
c
thuc
tu
xng, cc l'
bo T. NK,
mt s' t bo
B
Cc tp hp
con t bo T.
cc t bo B
hot ho

55

L th th i lc Pcel^II
thp cho IgE,
iu ho s tng
hp IgE, l cu
t gn cho ng
thu Ih' CD19;
C D 21:C D I8

Lectin
dng c

1
i
1
I
i1
ii
1
i

Cha r

Th
tng
ng
ngi
ca
khng
nguyCMi
n nhit
chut
(USA)
CCP
Chui a ciia thu l'ac
th IL-2

i
1

110

55

DiXpti- Glycoiro- ;
c t c c d i p e p t i t dvl pep- tein
X-Pro hay X- i'daza IV xuyn
;|
mng
i
Ala u N t cc
polypcptit
dang 11.
Lin kt vi
Thu
Ihc
CD70, c th
TNF
hot ng nh
1
mt cht dng
kch thch i

vi cc t bo B
%rr^
!
v r.
1
Ffo]l lia ac l' bo Tp 44
Immu
T ngu>i iii. l
noglobu- ii
i tl \i ac
lin
v 1
ti liiii ng kch
CD86

idi (Un liiu 2), lin

(B7.2)
k virD80(B7.1)
\CD86(B7.2)
Exopcptidaza.

44

C)29

Bch cu

CD30
1!

Cc t' bo 'I'.
B. NK hoi
ho
. cc
bch cu tUtn
nhn

CD3I

CD32

CD33

CD34
1
CD35

Cc bch cn
n
nhn,
cc tiu cu.
bch cu ht.
tp hp con
t bo T, cc
t bo t bo
ni m
Cc bch cu
n
nhn,
bch cu ht,
cc t bo B,
bch cu a
axit

130

Di n \ in
tegrin i 1, k
hi \i CD49a
inicgrin VLA1
120
Lin k \ i Ki-1
CD30I.
(CDIfi3). CD30
1CI1 k cho
i tng cng s
nhn di ciia t
bo B \' T
130-140 L phn l kt PECAMdnh, l trung !
gian tng tc
gia bci cu t bo ni m \
t bo ni m t bo ni ni.
40

L tlui tl I'c i IcyRII

lc Ihp i \'i
cc
immuIioglobiiliii kt
hp \'i nhau:
phc
min
dich
1j n k vi Sialoconjugate

Iiitcgriii

riui
TNF

the

ImmuIioglobulin

Immiinoglobulin

67
Cc t bo t
tin
dng
tu, cc bch
cu tlii nhn
Cc tiii t' 105-120 l, cu l gn
bo to mu,
cho CD62L (Lseleciin)
ni mi mao
1
mach
250 'l li ihc b th CRI
llng cu, t
1. lin kt vi
bo B, bch
C3b v C4b. lm
cu clcm nhn,
trurm gian cho
hch
cu
s Ihc bo
truiig
tnh,
bch cu ira
axit, cc t
bo tua nang

j
1

Immunogobulin
Mucin

CCP

240

CD36

Tiu
cu,
bch cu n
nhn, cc l
bo ni m

8S '

I Phn t kcrdnh <PV,

I licu
cu: bao C P I l l b
gm
snhn
ilcHi cu
bil

\'

Ihc

bo cua cc l j
bo
chcl
c
i

CD37

| m h _________

Cc l bo B 40 cira ro C(> ilc

irirng Ihiih,
! li n l u a n d n s i
cc t bo ' I
Iruycn
tn liiu,

'
1
Irirng thnh, 1
1 lo itiiih phc
; li viVi CD53.
cc t bo
(')S1. t;i)82 v
dng tu
M lIC l p ll
Cc t bo B
43
NAI) glycohy- fn o
(.lrolaza,
lin
v T s cp,
cc l' bo ''
lng s nlin (ii
hot
lio,
; Ic bo l
hcli cu
Cc t bo \i
78
C lira , C ihc
hot ha, cc
lm iniim eiaii
t bo NK
cho SII kei dnh
ca cc l bo
hot ho, di
tlic bo .
cc t ba
tua
Cc t bo B.
48
l.in
kl \i
i thc bo,
CD154
cc t bo
(CD40L), l Ih
tua. cc t'
ttc cho (n hiu
bo biu in
(ig kch thch
c bn
di \i cc t
bo
B,
kch
ihch s sinh
irng, s bii
ho, s iig m
isolVX' ca cc
t bo l, \' s
lo ihnh cytoki ne bi cc i
ihc bo \ cc
l bo lua

_____

I^rolciii

xuyn qia
mng
4
ln

CD38

CD39

CD40

ii
1

>

rh
TNF

Ilc

241

Integrin a
Inlcgrin alb, kt GPIb
hp vi CD6I
to ihnli GPIIb,
liCn kt vi fibrinogcii.
fi1broneclin. yu t'
\on Willcbraiid,

thronibospcindin
l ' M2~ : ricLi ciL t ^a:2 3 l.in ki \'i yu i; Cl^IX on lp
nhn h: 135. l von Wille- b: GPIba giu Leula.b.c.d i bo
1
khng 16
hiaii(.l. thrombin, c: (Pbp cine
1 23
cn
ihit cho s d: GPV
c:
22
i

d: 85 1 kt dnh tiu cu
cc v tr tn
ihii
115-135
cu,
C cu trc ko Leuc:D43 Bch
Mucin
ngoi tr cc (bch cii di, di khong kosianin
1
t bo B imhi trung 45 mn \' c llie sialoi
tnh) l chl chng phorin
95-115 dnh
(cc t
bo T)
cu, 80 - 05 Liii kt vi axit <hng
C'D44 Bch
Protein
hng cu
hyalurronic, lm Iguycn
lin kt
trung gian cho Hemes,
s kt dnh ca Pgp-I.
cc bach cu
CD45 T c cc te 180-240 'IVnKii
phot- Khng
Pibronectin

bo to mu
(nhicu PIUUEUk'ui lngs nguyn dng 111
ng tniyCi tn hiu qiui ph bin
dng) U i kliiUig bach cu
nguvn CUI GC t (LCA),
bKiBvT.tiihiu r200.
diig (Lmg do s B220
!
pliiicatluipliin
c:D45 'lip hp con
180 ng dang ca
Pibronectin
RO l bo T, tp
CD45
khng
dng H
hp con l
cha exon A, B,
bo B, bch
c no
cu
dn

i
nhn,
di
Ihirc
bo
1
CD4I

tc Dinicr:
bo
nhn GPIlba:
khng 16
i25
GPIbb:
22

'riCHI Cu,

242

CD45
RA

CD45
RB

CD46

Cc t bo B
\ lp hp
con t bo
'Idc bo T
nguyn
thu), bch
cu n nhn
Tp hp con
t bo T, l'
bo l, bch
cu
n
nhn,
i
thc
bo,
bach cu hal
Cc l' bo c
nliii to mu
v khng to
mu

20^ - 2( ng dng ca
CD45 cha exon
A

Pibronectiri
dng l

190-220 ng dng ca 1200

CD45 cha exon
B

ribroneciini
dng II

56/66
(cc bin
ihc phn
ct)

CCP

L protein ng MCP
yu t mng,
!icn kl vi C3b
v C4b clio php
phn hu chng
Iih vu t I
CD47 '1't c cc t 47 - 52 Phn t kt AP,
bo
dnh, th th MKR6.
thrombospondin 0A3
CD48 Bch cu
4 0 - 4 7 Cu t gn gi Blast-1
nh cho CD244
CD49a C c t b o T
200 Integrin a l, kt VLA-1
hot
ho,
hp vi CD29.
bch cu n
lin kt vi conhn, t bo
lagen, lam inin-1

Siu
l(J
imniunoglobuliii
Immunoglobulin
Integrin a

thn kinh, c

trn
CD49b Cc t bo B;
bch cu n
nhn;
tiu
cu; t bo
nhn khng
l; cc t bo

thn

kinh,

biu mf ni

m; t bo
hu xng

160

Integrin a2. kt
h(;p vi CD29.
lin kt vi colagen. aminin

VLA-2,
Integrin
GPIa tiu
cu

(X

243

Cl)49c Cc t bo B,
nhiu t bo
dnh bm

j
|Cl)49d l^lin b rng
bao gm cc
1!
t bo B, t
i
bo tuyn c,
bch cu dii
nhn,
bch

cu ht, cc

j
t bo tua
Cl)49c Plin b rng
bao gm cc
t bo T ghi

nh.
bch
cu
n
nhn,
tiu
cu
c:i)49f T
bo
l m h o

CD50

125,30

150

Integrin a

Integrin a

135. 23

ntegrin 'x5, kt VLA-5

hp vi CD29.
lin kt vi fibronectin, invasin

Integrin a

125, 25

Integrin a 6 , ,.t VLA-6

hp vi C D l,
lin
kt
V. i
laminin, invasit.
merosine

Integrin a

130

Lin kt vi ICAM-3
CD 1U /CD I8
integrin

Immunoglobulin

T.

bch cu n
nhn,
tiu
cu. t bo
nhn khng
l,
nguyC11
bo
dinh
dng
r bo tuyn
c. cc t bo
B, cc t bo
T, bch cu
n
nhn,
bach cu hat

Integrin a 3 . kt VLA-3
hp \'i CD29,
lin
kt
vi
laminin -5, fibronectin, colagen,
entactin,
invasin
Integrin a 4 , k VLA-4
hp vi CD29.
lin k\ vi fibroneclm, MAdCAM-1
VCAM 1

244

CD51

CD52

CD53

Tiu cu, t
bo
nhn
khng l

125, 24

T bo tuyn
c, cc t bo
T, cc t bo
B (khng c
t
bo
plasma),
bch cu cm
nhn,
bch
cu ht, tinh
trng (spermatozoa)
Bch cu

25

3 5 -4 2

Integrin aV , kt
hp vi C D 61,
lin kt vi vitronectin, yu t'
von Willebrand,
ibrinogen,
v
ihrombospondin;
c
th l th th
cho cc t bo
cht c chng
trnh.
Cha r, l ch
cho cc khng
th m c s
dng lm suy
yu cc t bo T
t tu xng

Cha r

rh

th Integrin a

vitronectin

CAMPA

TH-1,
HES

MRC

DX44
CD54

CD55

Cc t bo
lo mu v
khng
to
mu

75-115 Phn t kt dnh ICAM-1

Cc t bo
to mu v
khng
to
mu

6 0 -7 0

ni

bo.

Protein
xuyn qua
mng 4 ln
Immunoglobulin

(ICAM)-l, lin
kt vi integrin
C D lla/C D 18
(LFA-1) v integrin
C D lib/C D 18
(Mac-1), Ih th
i vi rhinovirul
Yu t' tng cng DAF
pin hu (DAF),
lin kt vi C3b,
phn hu convertazaC3/C5

CCP

245
t bo 135 - 220 ng dng ca
phn t ict dnh
t bo thn kinh
(NCAM), phn
t kt dnh
CP57 Cc t bo
Oligosacarit,
c
tm thy
NK, Tp hp
trn nhiu glycon cc t
coprotein b mt
bo T, cc l'
t' bo
bo B, v
bch cu n
nhn
CP58 Cc t bo 5 5 - 7 0 Khng nguyn 3
kt hp chc
to mu v
nng bch cu
khng
to
(LFA-3),
lin
mu
kt vi CD2,
phn t kt dnh
19
Lin kt vi cc
CD59 Cc t bo
to mu v
thnh phn b
th C8 v C9
khng
to
ngn cn s kt
mu
hp ca phc h
tn cng mng
Disialyl
ganCT60a
glioside
D3
(GD3)
90-acetylCD60b
GD3
CP56

Cc
NK

crOc
CD61

7GD3
Tiu cu, t
bo
nhn
khng l, di
thc bo

110

O-acetyl-

Di n v P3
integrin, kt hp
vi
CD41
(GPlIb/lIIa)
hoc CD5I (th
th vitronectin)

NKH-1

Immunoglobin

H N K -l,
Leu-7

LFA-3

Immunoglobulin

Protectin, Ly-6
cht
c
ch Mac

Cu
trc
carbohydrate
Cu
trc
carbohydrate
Cu
trc
carbohyrale
integrin p

246

CD62E Ni m

140

CD62L Cc t bo B,
cc t bo T,
bch cu n
nhn, t bo
NK

150

CD62P Tiu cu. l

bo
nhtt
khng l, ni
m

140

CD63 Tiu cu hot

ho,
bch
cu
cm
nhn,
i
thc bo
CD64 Bch cu cm
nhn,
i
thc bo
CD65 Cc t bo
dng tu

53

Phn t kt dnh KLAMbch cu ni m 1.

E(LAM), lin selectin
kt vi sialylLewis\
lm
trung gian cho
s tng tc ln
ca cc bch
cu trung tnh
trn ni m.
Phn t kt dnh LAM-1,
bch
cu E(LAM), lin kt selectin,
vi CD34, Gly- LECAMCAM, lm trung 1
gian cho s
tng tc ln vi
ni m.
Phn t kt pdnh, lin kt vi electin,
GDI62 (PSGL- PADCiE
1), lm trung M
gian cho tng
tc ca tiu cu
vi cc t bo
ni m, bch
cu n nhn,
v bch cu ln
trn ni m
Cha r, l pro- Khng
tein mng ly- nguyn
sosom
chuyn pot ho
ti b mt t' bo tiu cu

Lectin
dang
EGF,
CCP

c,
v

Lectin
dang
EGF,
CCP

c,
v

Lectin
dang
EGF,
CCP

c,
v.

Protein
xuyn qua
mng 4 ln

sau khi hoat ho

72
Thnh phn oligosacarit
ca
ceramide
dodecasacarit

247

CD66a Bch
cu 160-180 Cha
r,
l
trung tnh
thnh vin ca
h
khng
nguyn phi ung
th (CEA)
Bch
cu
ht
CD66b
95-100 Cha r, thnh
vin
ca
h
khng
nguyn
phi ung th
(CEA)
cu
CD66c Bch
90
Cha r, thnh
trung
tnh,
vin
ca
h
ung th biu
khng
nguyn
m rut kt
phi ung ih
(CEA)
1

>

cu
CD66d Bch
trung tnh

CD66e Biu m rut

kt
ngi
trng thnh,
ung th biu
m rut kt
CD66f Cha r

CD68

CD69

1blycoprotein-1
mt
(BGP-1)

Immunoglobulin

CD67
Immutrc y noglobulin

Khng
Immunguyn
noglobulin
phn ng
cho
khng
c hiu
(NCA)
30
Cha r, thnh
Immuvin
ca
h
noglobulin
khng
nguyn
phi ung Ih
(CEA)
1 8 0 -2 0 0 Cha r, thnh Khng
Immuvin
ca
h nguyn
noglobulin
khng
nguyn phi ung
phi ung th th
(CEA)
(CEA)
Cha r, thnh 1GlycoImmunoglobulin
vin
ca
h protein
khng
nguyn c hiu
phi ung th thai
(CEA)
110
Cha r
MacroMucin
sialin

ci on
nhaithLCh),
biciDUgtih
, hch ci IK
kin, cc t bo
l>nr)lDii
Cc t bo B 28, 32 Cha r, khng
v T hot hom odim nguyn hot ho
ho, cc t
er
giai oan u
bo NK v
...........................

'

Phn t Lectin
cm mg dng
s hot
io

248

CD70

hoat ho
Cc t bo B
v T hot
ho, v cc
ai thc bo

Cu t gn cho Ki-24
CD27, c th c
vai tr ng
kch thch cc t
boB vT
CD71 Tt c cc t
95
Th th transfer T9
bo
ang homodim rin
nhn
i.
er
bch
cu
hot ho
CD72 a c t bo B
42
Cha r
Lyb-2
(khng phi homodim
cc t bo
er
plasma)_____
C)73 1'p hp con 69
Ecto-5't bo B. lp
nucieotidaza,
hp con l
dephotphoryl
ho cc niicleobT
til cho php thu
nhn nucleozit
CD74 Cc t bo B. 33, 35. Chui khng i i, ly
di thc bo, 4 1 ,4 3 kt
hp
vi
bch cu n (s khi MHC lp 1!
nhn, cc t du v
bo kt hp phn ct
vi MHC lp
lun
II
phin)
CD75 Tp hp con
Lactosamin, cu
cc t bo B.
l
gn
cho
cc t bo 'I'
CD22, trung ho
trirng thnh
s kt dnh t
bo B-t' bo B
CD75s
Lactosamin sialyl ho a-2.6
CD77

Cc
bo B
gia thi
kv phi thai

73. 95,
170

Glycosphingol- Nhm
ipit trung tnh mu Pk
lOlo(G a la l-
x)trao4Galpl^
4G alcpl -> ce- :yl- ceramide) lin kt amid
vi dc t' Shiga. (Gb3)

TNF

Lectin
dng

Cu
trc
cacbohydrate

249

vi c t Shiga,
lin kt cho
cm
ng ci
cht c chng
trnh
CD79 Cc t bo B a : 40 -45 Thnh phn ca
th th khng
a ,p
p :3 7
nguyn t bo B
tng ng vi
CD3, cn thi
cho s biu hin
b mt t bo v
s truyn tn
hiu
60
L cht ng
C'D80^ Tp hp con
kch thch, cu
t bo B
t gn cho CD28
v CTLA-4
26
Kt
hp vi
CD81 Cc t bo
CD19, CD21
lympho
to thnh dng
th th t bo B

CD82

Bi.ich cu

Cc t bo tua,
cc t' bo B,
cc t bo
Langerhans
CDw84 Bch cu n
nhn.
liu
cu, cc t
bo B tun
hon
c:d 83

CD85

Cc
tua

bo

g a. IgP

Immunoglobulin

Immunoglobulin

50 -53

Cha r

B7 (ngy
nay;
B7.1),
BBl
ch ca
cc
khng
th
khng li
ur nhn
doi
(TAPA1)
R2

43

Cha r

HB15

73

Cha r

GR16

Immunoglobulin

H ILT/LIR

GR4

Siu
h
Immunoglobulin

Protein
xuyn
mng 4

Protein
xuyn
mng 4
Immunoglobulin

250

CD86

Bch cu n
nhn, t bo
B hot htn.
cc t' bo
tua
CD87 Bch cu ht,
bch cu (l(n
nhn,
i
thc bK. cc
t bo T, NK,
mt lot cc
dng t bo
kling
to
mu
CD88 Bch
cu
nhiu
dng
nhn.
i
thc bo. t
bo Mast
CD89 Bch cii (Icrn
nhn,
ilai
thc
b.o.
bch cu liat.
bch
I..III
trung
tnli.
tp hp Cdii
l bo B. tp
hp con tc
bo T
CD90 Tin C' bo
tuyn
c
C34*
(ngi).
t'
bo tuyn c,
l
bo
1
(chut)
CD91 Bch cu (tn
nhn, nhiu
t bo khng
tao mu
CD92 Bch
cu
trung
tnh,
bach cu om

80

35 - 59

Cu t gn cho B7.2
CD28
\'
C1LA4

Immunoglobulin

Th th cho cht iiPAR

hot
ho
urokinazu plasminogen

Lv-6

I
43

50 - 70

Th
th
cho C5aR
thnh phn b
th C5a

rii
tli
cp
(li
\ i
protein G

Th th IgA

Immii
noglohiilin

F caR

18

Cha r

Thy-1

515. 83 'Ih
ih
u2
; inacroglobiiliii

.........
if

Immunoglobulin

1
11
1
!

70

Cliira r

GR9

i
<Thu
iIK|
; l-Xil-. i .ni

251

nhn,
tiu
Cilu, ni m
cu
C l 3 Bch
Iriiiig
tnh,
bch cu (t(n
nlin, Iii m
C IW 4 ' Tp hp con
1i
1 t bo 1 \ tc
bo NK
lot
( t o "i Mt
(liig l bo,
phn b' in
1
vivo cha r
riii
i
C'1X>(> Cc l hau T
.
i

! liiiat KK. t
bioN K
1

C'D97

........

120

Cha r

G R ll

43

Cha r

KP43

45

Lin kt vi cu Apo-1.
t gn Fas ging Fas
TNF, gy ra ci
cht c chng
trnh
Cha r
Biu hin
mun
tng hoi
ho
t
bo
T
(T A C riL
)
U n
kt
vi G R l

160

Cc t bo B 75 - 85
1 \
1 hot
1
1 ho.
bch
i
cu
dn
1(
Iihn.
bch
cu hat
Cc t' bo 80. 45
hetB;r. t ho
git l nhin, erodim er
bch cu ht,
lt c cc (lng
t' bio ngi
Cc t bo
c: )9 9
32
lym pho mu
ngoi vi, t
bo tuyn c
150
Cc
t bo
CDIOO
to mu
hom oim
er
120
CDIOI Bch cu n
nhn,
bch homodim
cu ht. t'
er

Lectin
dng c
Thu
INI-

th

Immunoglobulin

E-GF. ch
th
cp
di
vi
protein G

C th l cht 4F2,
vn chuyn axit FRP-1
amin

i a r

M .C 2,

Cha r

C.R3

Semaphorin

Cha r

BPC#4

Im m unoglobulin

252

CD102

CD103

CD104

CDI05

bo tua, t
bo T hot
ho
Gc t bo 55 - 65 Lin kt vi ICAM-2
CDlla/CD18
lympho ngh,
(LFA-1), nhng
bch cu n
nhn, cc t
khng lin kt
vi
bo ni m
CDlIb/CD18
c
mch
(mnh nht)
(Mac-1)
Cc t bo 150, 25 Integrin aE
HML-1,
lympho ni
integrin
biu m, 2a6, aE
6% cc t
bo lympho
mu ngoi vi
T bo tuyn 220 Integrin P4 ktlK
c 0 4 . CD8,
hp vi CD49f, tegrinP4
cc t bo thn
lin kt vi cc
kinh, biu m,
laminin
v mt s' t
bo ni m,
cc t bo
Schwann,
nguyn bo
dinh dng.
Cc t bo
90
Lin kt vi Endoglin
ni m. cc homodim TGF-P
er
bch cu n
nhn v i
thc bo hot
ho , tp hp
con

cc

Immunoglobuiin

Integrin X

Integrin(;

bo
tu
xuomg
CD106 Cc t bo 100-110
ni m
Phn t kt

CD107 Tiu cu hot

a
ho, cc t
bo T hoat

110

dnh, cu t gn
cho VLA-4 (integrin 043 ,)
Cha r, l pro-

VCAM-1 Immu-

F*rotein
tein mng ly- mng 1
sosom
chuyn lin kt

noglobuln

253

ho,
bch
cu
trung
tnh
hot
ho, ni m
hoat ho
CD107 Tiu cu hot
ho, cc t
b
bo T hot
ho,
bch
cu
trung
tnh
hot
ho, ni m
hoat ho
CD108 Hng
cu,
cc t bo
lympho tun
hon, nguyn
bo lympho

ti b mt t bo lysosom
sau khi hot ho (LAMP1)

120

Cha r, l pro- LAMP-2

tein mng lysosom
chuyn
ti b mt t bo
sau khi hot ho

80

Cha r

CD109 Cc t bo T
hot ho, tiu
cu hot ho,
ni m mach
C D llO Tiu ciu
C D lll Cc l bo
dng tu
CD112 Cc t bo
dng lu
CD114 Bch cu ht.
bch cu n
nhn

170

Cha r

CD 1I5 Bch cu n
nhn,
i
thc bo
1

150

CD116 Bch cu n
nhn,
bch
cu
truii 2
tnh,
bch
1
cu a axit,
tii m

70-85

GR2,
Khng
nguyn
nhm
mu John
MillonHagen
Nhn t
hot ho
tiu cu,
GR56

MPL, TPO R
PPR l/N ectinl
PRR2
150

Th th yu t'
kch thch dng
bach cu hat (GCSF)
Tli th yu t
kch thch dng
ai thc bo (MCSF)
Chui a th th
yu t kch thch
dng bch cu
hat - ai thc
bo (GM-CSF)

Immunoglobulin,
ibronectin
dng III
M-CSPR Immuc-fms
noglobulin,
tyrozin
kinaza
Th th cyGMtokine, fiCSFRa
bronectin
dng III

254

CD117 T lin t
bo to mu
j

145

Th th yu t t C-Kit
bo
ngun
(SCF)

Immunoglobulin,
tyrozin
k in a 7 .a

Th th inter- INFCD118 Biu hin t

bo rng
a.PR
feron a,3
CDI19 i thc bo, 90-100 Th th inter- 1NF-R Pibronectin
dng III
bch cu n
feron-
nhn, t bo
B. ni m
l
CD120 Cc t bo 50-60 'lli th TNF, TNPR-l Thu
lin kt \i c
TNF
to mu v
a
khng
to
TNF-a v TN-mu,
cao
p
nht cc t

bo biu m
th
CD120 Cc t bo 75-85 Th th TNF, TNFR-[[ Thu
i 'I-NIlin kt vi c
to mu v
b
!

khng
to
TNF-a v TNFi
mu,
cao
p
nht cc t
i
bo dang tu
80
Th Ih inter- IL-IR
CD Cc t bo
ImniuI
noplobulin 1
121a tuyn c. t
leukin- dng I, dng I
lin
kt
vi
ILboT
1
lavIL-13
CDw Cc t bo B, 60^70 Th th inter- IL-IR
Immii121b i thc bo,
leukin-l dng II. dng II noglobulin
lin kt vi ILbch cu n
nhn
lavIL-10
CD122 Cc t bo
75
Q iui p thu th IL-2RP ITi th cyNK, tp hp
tokine, fiIL-2
con t bo T
bronecthn
ngh, mt s
dng III
dng t bo
B
CD123 a c t bo
70
Q iui a thu th IL-3Ra TTi th cyngun
tu
tokine, fiIL-3
xung, bch
bronectiin
cu ht, bch
dng III
cu n nhn,
t bo nhn
khng l

255

IL-4R
CD124 Cc t bo B 130-150 Th the IL-4
v T Irirng
thnh, cc t

bo tin to
mu
IL-5R
CD125 Bch cu a 55-60 Th th IL-5
axit,
bch
cu a kim,
cc t bo
hoat ho
80
CD126 Cc t bo B
Di n v a IL-6 R a
hot ho \'
th th IL - 6
cc t bo
plasma
(mnh), phn
ln bch cu
(yu)
1
IL-7R
GDI 27 Tin lymplio 68-79 Th th lL-7
tuv xirng, tc c kh
bo ticii B, t nng to
!
bo T trng homodim
ihnh, bch
er
cu dn nhn

CDw
128

Bch
cu
Irung
tnh,
bch cu a
kim, tp hp
con t bo T
CD129 Vn
cha
c
xc
inh
CD130 Phii ln cc
dng t bo,
mnh
trn
cc t bo B
hot ho \'
cc t bo
plasma

.S8-67
1

Th ih cytokine, fibroncctin
dng 111
Immunoglobulin.th th
cytokine,
ibronectin
dng Ili
Hibronectin
dng III

Tli th IL - 8

1L-8R

Tli
th
cp i vi
protein G

Di dn v
chung ciia lL- 6 ,
IL -II
on
costalin-M
(OSM) v a c
th Ili yu t c
ch bnh bch
cu (LIF)

iL- 6 Rp.
ILIIR P .
OSMRp,
LIFRp,
IFRP

Iiiimunoglobulin.
th ih cytokine,
ibronectin
dng III

130

Th Ihc cytokine. fibroncctin

dng III

256

CDvv
131

T tin t
bo tu, bch
cu ht

CD132 Cc l' bo B,
cc t bo T,
t bo NK, t
bo
Mast,
bch
cu
trung tnh
CD133 Cc t bo
ngun/
t
tin
CD I34 Cc t bo T
hot ho

140

64

Di n \' p
chung ca IL-3,
IL-5, v cc thu
th GM-CSF

IL-3RP,
lL-5Rp,
GMCSFRp

Th th cy
tokinc. fi
broncctin
diig 111

Th ih cylokinc

Chui 7 th th
IL-2, di dn
vi chung ca cc
thu th IL-2, IL4, IL-7, IL-9, v
lL-15
AC133

50

C
th
hot 0X 40
ng nh mt
cht ng kch
thch phn t kt
dnh
CD135 Tin ihn t 130.155 Th th yu t FLK 2 ,
bo a nng,
sinh trng
STK -1
t tin t bo
B v bch

Thu
TNF

i1

ilni
!

Iinmu-

noglobulin.
tyrozin
kinaza

cu n nhn
dng tu
CDu
136

CDw
137

Bch cu n
nhn, t bo
biu m. h
thn
kinh

trung ng
v ngoi vi
T bo lympho B v T,

bch cu n
nhn, mt s

t bo biu
m

180

Ho
hng MSP-R,
dng, s thc kO N
bo. sinh trng

Tyrozin
kinaza

t bo, v bit
ho
Cht dng kch ILA
Thu
thch s nhn (c
TNF*
i l bo T
cm ng
bi
s
^ot ho
t
bo

lympho),
4-lB B

th

257

( D138 'I' bo B

T bo B
C D I40 T bo m,
a,b
mt s t bo
ni m

Cc t bo
ni m c
mach

CD14I

Cc
iin kt
hepran sulphate
prteoglycan,
collagen dns 1
209, 228 Cha r
a: 180 Chui a v p
b;180 th th yu t
sinh
trng
ngun gc tiu
cu (PDGF)
105
Cht
chng
ng, lin kt
vi
thrombin,
phc h sau
hot ho protein

Syndecan -1

Thrombo Lectin
modulin dng
toEGF
modulin

CD142 T b kera- 45 - 47
lin biu m,
cc ( bo
biu m khc
nhau, t bo
dng sao, t
bo
Sch\vaiin.
Khng c
cc t bo
lin h trc
tip \'i bo
tng.tr khi
c to ra
bi cc cht
trung
gian
phan
ng
v i m . _____
03143 Cc t bo 70'-180
ni
m,
ngoi Ir cc
mch
mu
ln v thn,
cc t bo
bicu m ca
m p llii v

Nhn t khi
du chnh ca
hin tng dng
cc. Lin kt vi
yu t Vlla,
phch ny
hot ho cc yu
t VIi, IX, v X

Yu
to Pibronectin
m,
dng III
hromboplastin

Pepiidaza
kim
loi Zn dipeptidyl peplidaza
, phn ct angiotensin I v bradykinin t cc
dng lin thii

enzym
chuyn
ho angiotensin
(ACE)

258

rut non, t
bo
thn
kinh.
i
thc bo hot
ho v mt
s t bo T.
Dng ho tan
trong
bo
tng
CD144 O c t bo
ni m

CD145 Cc t bo
ni m, mt
s' t bo
m
CDI46 Ni m

CD147 Bch
cu,
hng
cu,
liu cu, t
bo ni m

CD148 Bch cu ht.

bch cu n
nhn, t bo
tua, t bo T,
nguyn bo
si, t' bo
thn kinh
CDI50 Cc t bo
tuyn c. cc
t bo lympho hot ho
CD151 Tiu cu, t
bo
nhn
khng l, t
bo biu m,
t bo ni m

130

25. 90,
110

Thit lp ch
ni ki dnh
cc t bo ni
m
ia r

1 Plin t c kh
nng kt dnh,
nh v ch ni
t bo - t bo.
55 - 65 Phn t c kh
nng kt dnh
130

Cadherin-5,
VEcadherin

Cadherin

MCAM. ImmuMUC18, noglobulin

S-ENDO

M6, neu- Immurothelin, noglobulin

EMMPR
IN.
pasigin.
bX -47
Pibronectin
2 4 0 -2 6 0 c ch lin h s HPTPri
dng
111
sinh trng ca
protein ty
l bo
rozin phot
phataza

75 - 95

32

Cha r

SLAM

Kl hp vi in- PETA-3,
SFA-i
tegrin pl

Immunoglobulin

Protein
xuyn
mng 4

259
CD152 Cc t bo T
hot ho

33

Thu th cho CTLA-4

B7.1
(CD80).
B7.2
(CD86);
cht iu ho
m tnh s hot
ho t bo T
Cu t gn cho CD30L
CD30, c th
ng kch thch
cc t bo T

CD153 Cc l ba T 38 - 40
hot ho, i
thc bo hot
ho,
bch
cu
(rung
tnh, t bo B
CD154 Cc t bo T- 30 dng Cu t gn cho
CD4
hot trimer CD40, cht cm
ng ca s hot
ho
ho v nhn i
t bo B
nng
CD155 Bch cu n 8 0 - 9 0 Chc
thng
thng
nhn,
i
cha r. th th
thc bo, t
cho poliovirut
bo tuyn c,
cc
noron
CNS
69
Cha r, c th
cu
CD156 Bich
lin quan n s
a
trung
tnh,
trn dch bch
bch cu dn
nhn
cu integrin (integrin leukocyte
extravasation)

CD
I56b
CD157 Bch cu ht,
bch cu n
nhn, t bo
m
tu
xng, t bo
ni m c
mch, t bo
tua nang

CD40L,
TRAP,
T-BAM,
gp39

Immunoglobulin

TNF

Thu
t n 'f

th

Th th ImmuX)10noglobulin
virut

MS2.

ADAM 8
(mt proteaza kim
loi
v
khng
phi inegrin)

TACE/ADAMl
7; cu trc kt
dnh
4 2 - 4 5 ADP-ribosyl cy- BST-1
(50
c!aza,
ADP
bch cu vng-ribo7. hydolza
dn
nhn)

260

CD158 T boN K
CD158 Tp hp con
tb oN K
a

Ho KIR
50 hoc c ch tnh c p50.1,
58 ' t bo NK trn b58.1
cc
phn
t
MHC lp I lin
kt

CD158 Tp hp con
b
t bo NK

50 hoc
58

CD159 Cc
NK
a

bo

CD160 Cc t bo T
CD161 a c l b o N K ,
cc t to T
CD162 Bch
cu
trung tnh, t
bo iympho,
bch cu n
nhn
CD162 Cc t bo
NK
R
CD163 Bch cu n
nhn,
i
thc bo
CD164 Cc t bo
biu
m,
bch cu n
nhn, cc t
bo m tu
xng
CD165 T bo tuyn
c, t bo
biu
m

c ch tnh c p50.2,
t bo NK trn b58.2
HLA-Cw3 lin
kt v cc alen
iin quan
Lin kt vi NKG2A
CD94 to
thnh th th
NK; c ch tnh
c t bo NK
trn cc phn t
MHC lp I lin
kt
BY55
44
iu ho tnh NKRPl
c t bo NK
120 dng Cu t gn cho PSGL-1
homodim CD62P
er

Immiinoglobuliri

Immunoglobulin

Lectin
dng
Mucin

PEN5
130

Qia r

M130

80

Qia r

MUC-24 Mucin
(protein
24 c
da glycosyl ho)

37

Kt dnh gia t Gp37,

bo tuyn c v AD2
biu m tuyn

261

tuyn rc, cc
noron CNS.
o tu, v
Bowman
CD166 Cc t bo T 100 -105
hot
ho,
biu
m
tuyn
c,
nguyn bo
si, cc noron
CD167 Cc t bo 63, 64
a
biu m bnh
dng
thng
v dimer
bin oi

Cu t gn cho
CD 6 . bao gm
s ko di dy
thn kinh integrin

ALCAM, ImmuBEN,
noglobulin
DMGRASP,
SC-1

Lin kt vi co- D D R l,
Tyrozin
lagen
rkE, cak, kinaza th
eddrl
th,
discoidin lin
quan
CD168 Cc t bo 5 ng Phn
t
kt RHAM
ung th v
dng;
dnh. ITi
M
58, 60, th cho s vn
64, 70. ng c trung
84
ho bi axit hyaluronic
s
dch chuyn t
bo trung gian
CD169 Tp hp con
185
Phn
t
kt Siaload- Siu
h
i thc bo
dnh. Lin kt lesin
immuvi cacbohydrat
nogobulin,
sialyl ho, c
h siaoadth lm trung
hesin
giaii cho s lin
kt i thc bo
vi bch cu ht
v t bo lympho
CD170 Bch
cu 67 dng Phn
h
t
kt Siglec-5. Siu
trung tnh
hornodim dnh.
Lectin 0BBP2, immuer
ging Ig lin kt CD33L2 noglobulin,
axit
sialic
h siaload(Siglec).
ui
hesin
nm trong vng
t bo cht cha
motif (vng bo
th) ITIM

262
Phn
t
kt L l.
200 CD171 Noron, cc t
dnh, lin kt vi NCAM220
bo
CD24, L l
Schwann, cc TLPT CD9,
CD56, cng l
t bo lymchnh
pho v bch xc thay lin kt liomocu cfn nhn i theo philic
dng tu, cc dng t
bo
t bo B, cc
t bo T CD4 (khng
phi t bo
T-CD8)
115-120 Phn
t
kt SIRP,
CD172
dnh,
proiein SHPSl,
xuyn mng l IMYD-1.
c cht ca ty- SIRP-arozin kinaza th 1. c cht
th hot ho dng
(RTKs) v lin chng thi
kt vi cc do- th
rolein
main SH2
yrozin
hot>hataza I
PTPNSl)!
CD173 Tt c cc t
Nhm mu H
bo
type 2,
phn
hydratcacbon
CD174 Tt c cc t
Nhm
mu
bo
Lewis y, phn
hydratcacbon
CD175 Tt c cc t
Nhm mu Tn,
bo
phn
hydratcacbon
CD175 Tt c cc t
Nhm mu Sias
bo
lyl-Tn. phn hydratcacbon
CD176 Tt c cc t
Nhm mu TF,
bo
phn
hydratcacbon
CD177 Cc t bo 5 6 - 6 4 NBl
l mt NBl
dng tu
khng
nguyn
c hiu bach

Siu
h
iinmunoglobulin

Siu
h
Immu1
noglobulin

263
cu

tru n u tnh

lin kt ( i r i , chi
c tm iliay

bch cu nung

1
1

tn h

ngi
Ihnh

int
iniVmg
c

N B l(0 7' r imiri

1
cho kho) NM
(lc hiu tii
u lii giai
j
' Aoim w bo tuv
ciia qn rlnh
bil ln (l.im
ILIV

3S
42
C

c
t
bo
1
Cu
lu nn l*as, J asL
S ic u
ho
CD178
lin k( vi F;is
hot ho
'1NF
IIa\ ra Ciii ch!

^____
co chu\i^i
liili

^
_ . . w.L
.
- .,
1
6
-IS
CI
1
U
1
niiiiu! C I ) 1 7 9 Cc t bo B
VpivB,
S ic u
h
noglobiii kl hp jI(VPM,
nguyn thu
iinmu
k l n g cong ho ilgi
noglobulin
1!
ir v i C)179b
1
i!c tao ilnh ml I
i

CD179

r bo

chui nho thay

tl^ ll \l m(M
thnh plin cua
th ih lin t
ho B ciim \'ai
Ir quan Irni
1 giai don u
1 bit ho l bo H
I\>lypc|nit
1
\ uing
immu-

11

>

S ic u

IGLl .l.

X5(IGI.5< immii noilobulii;

1 loglohiilin kct

1iip

khng cni: I G V P B . t
1
ho
iri
\\ 4.
\
CD179a cc to
thnh mi chui
!

i
i

Iih ihav th
c b iai hin
mi cch chon
lc giai don

1
11
1

264

u ca s pht
trin t bo B.
Cc t bin
trong
gen
CD 17% dn ti
lm suy yu s
pht trin t bo
B v bnh thiu
globulin
gama
huyt ngi
CD180 T bo B

95-105

Protein
mng LY64,
dng 1 bao gm RP105
cc on lp
giu

Th
thi
ging loi
(TRL)

Leucin

ngoi
bo
(LRR). Kt hp
\i 1 phn t
c gi l MD1 v to thnh
phc h th th
b mt t bo
RP105/MD-1
.
hot ng phi
hp vi TLR4
iu khin s

nhn bit t bo
B v s truyn
tn hiu ca
lipopolysacarit

(s) '
CD183 c bit trn
cc t bo B
c tnh t
bnh ri lon
nhn
di
lympho mn
tnh

46 -52

CD184 Biu hin u

tin trn cc
t bo ngun
tao
mu

46 -52

Th th chtho
vn ng cxc,
lin quan n
ho hng ng
ca cc t bo
lympho B c
tnh. Lin kt
vi INPIO v
M IG'
Lin kt vi SDF1 (LESTR/usin),
hot ng nh
mt
cofactor

CXCR3,
th
th
cp i
protein G
9 (GPR9)|

Cc th thC
cht
ho
vn ng
Siu h th
th cp i
protein (

ICXCR4,
NPY3R,
LESTR,
fusin.

Cc ih th
cht
ho
vn ng
Siu h th

265

CD 34' cha
trng thnh
hn

CD195 Cc t bo
tii dng tii

40

(iig nhn t) HM89

cho s hp nht
v s tip nhn
dng l bo T,
chng dinh dng
caHIV - 1 .
Th th cho cht

ho \ii ng
dng cc. Lin
kt vi M lP -la ,
M lP -lp
v

RNTES.
C
th ng vai tr

th cp i
prolein C)

Cc th th
ho
vn
ng, Siu
h th th
cp
i
protein G

iu khin s
nhn di v bit

ho dng bch
cu ht. Hot
ng nh mt
dng th th vi

CD4 c lp
hng kch thch
i thc bo s
cap ca HIV-1
Th th cho cht
ho vn ng
MIP-3p. C the
ng vai Irl
yu t' trung
gian ca nhng
nh ling EBV
Icii cc t' bo
lympho B hay
cc hot ng
ca t bo lympho
bnh
thng.________
CD200 Cc dng t 41 (t bo Khng
nguyn,
bo B v no tuyn c uc nhn bit bi
chut), MoAb
MRC
bnh thng
47 (no 0X2. a c phn t
chut) khng cng dng
(nonlineage).
Chc nng cha r
: dw
197

Cc t bo
lympho B v
T hot ho,
diu
ho
m nh ln t'
bo
B
b
nhim EBV
v t bo T b
nhim H H V 6
hay7

46 -52

:CR7,
BIK
genl
dc cm
ng bi
virut EpsteinBarr),
ICMKBR
7, BLR2.

Cc th th
cht
ho
vn ng,
Siu h th
ih cp i
protcin Ci

MOX-2.
MOX -1

Siu
h
Immunoglobulin

266
CD 201

Cc

bo

49

ni m

T h th b m t E P C R

H phc h

bo

ni

p h h p t

co

kh

ch c

(E P C R )

n n g li n k t i
l c

cao
v

ch

yu C D 1

p r o ie in

p r o t e in

hot

ho.

i u

ho

g i m x u n g n h
ti p x c

ni m

v i y u t h o i
t u n g th ________
CD 202
b

Cc

bo

140

ni m

Tyrozin kinaza
th th, lin kt
vi
angiopoi-

VM CM ,
TEK

S i u h

(ty - im m u -

r o z in

n o g lo b u -

e tin -1,
quan k in a z a ,
lin , ly r o trng Irong vic n i m ), z in k in a?.a
hnh
thnh T E 2 (ty -

mch, c bit

r o z in

cho hnh thnh k in a z a c

h thng mch c c
dotrong cc t bo m a in

ni m. Nhng

t n g

khuyt
lt
ng
Ig
T E K i km vi v E G F ) .

nhng c th d
tt tnh mch di
truyn,
con
ng truyn tn
hiu TEK quan
trng cho s lin
c t bo ni

VM CM

m-t bo c
trcm trong qu
trnh to hnh
tnh mach
CD203

Cc

dng

tu (

cung,

bo
t

101

Thuc

m t

enzym

lo t

p r o t e in
xuyn

bch

bo

li n

quan

c u a k i m ,

th u

v c c t b o

phn

m a st)

c le o t it

cc

Cc

ngoi

nungoi

bo. C h n g x c

m ng
dng
h
p h o t-

II,
p y ro -

267

CD204 Cc t bo
dng tu

220

tc cho s phn
phataza/p
ct cc lin kt
hotphodiphosphodieste
esteraza
nucleotit.
v lin kt photngoi bo
phosunphat ca
cc phn t bao
(Egm deoxynuNPP)
cleotit, NAD v
cc gc ng
ca nucleotit
L m trung g ia n Yu
tc
H Ih
cho s li n kt, hu dr th n xc
s
tip
thu n xc thi (thu
( n u i) , v x l hi) dn).
mt lot cc i hc bc ging cop h n t tc h i n R
lagen
m. Lin quan ^M SR l)
n
s
lng
ng

bnh

hc

ca cholesterol

cc
thnh
ng
mch
trong qu trnh
h n h th n h b n h
x

v ia

ng

mach
Khng nguyn
CD205 Cc t bo
205
t bo lympho
tua
75. th th bt
gi
khng
nguyn gi nh
trn cc t bo
tua
CD206 i thc bo, 175-190 Glycofyotein
mng dng 1, v
t bo ni m
d bit duy
nht v lectin
diig c
cha
nhiu Q D duig
(cc domain
nhn bit cacbohydrat), n lin
kcl vi cc cu

ILY75,
DEC205,
IGP200V1R6

Protein
xuyn
mng
dng I

Siu h
Th th
mannoza lectin
i thc dng c
bo

(MMR),
MRCl

268

trc mannoza cao

trn b mt ca
cc vut, vi khun
v nm. c kh
nng Ry bnh.

CD207 Cc t bo
Langerhans

40

CD208 Cc t bo
tua an vo
nhau trong
cc bo quan
lympho

70-90

Protein
xuyn ^angerin Siu
hc
mng
mng
lectin
dng II, lectin
dng c
dng c c hiu
t bo Langerhans; cht cm
ng hiu qu
superimposiiion
and
zippering
mng dn n s
to thnh cc ht
birbeck - BG.
Tng ng vi ^otein
H phc
CD68^
DC mng k h
ph
LAMP l mt lp vi hp
t
ly- chc ch
protein lysosom D
yu
lin quan n sosom,
vic t chc li x : cc khoang x .AMP
l khng nguyn
chuyn ho v
trong trnh din
khng
nguyn
gii hn MHC
lp II, iu ho

mnh ln cc
DC trng thnh
c cm ng

bi

CD40L,

T N F-a v LPS

CD209 Cc t bo
tua

44

Lectin dng C;
lin kt vi v
ngoi ICAM3 v
HIV-1 glycoprotein gpl20 cho
php rng buc
th th t bo T
bng cch lm

DCSiu
ho
SIGN
lectin
p h i in- dng c
kgrin bl
gi
CAM3
c hit
t___ to

269

CD
W 210

Cc t bo B,
cc t bo T
b tr, v cc
t bo ca
dng
bch
cu
n
nhn/i thc
bo

90-110

CP212 Cc t bo
CD4, CD 8 ,
v NK hot
ho

130

C D 23 Cc t bo B,
al
bch cu dn
nhn, nguyn
bo si, t
bo ni m.

60 - 70

n cnh vng ua)

lin h DC-t
bo T, kch thch
s nhim hiu
qu cc t bo
trans m biu
hin cc th th
CD4 v th th
cli ho hng
ng;
protein
xuyn
mng
dng II_________
Th th inter- IL-IO Ra
leukin 10 a v p
ILlORA,
HILlOR. ILlORp.
IL-IORB,
CRP2-4,
CRFB4
Chui p th th IL-12R
IL-12,
protein 1L-12RB
xuyn
mng
dng 1 lin quan
n s truvn tn
hiuIL-12
Th th ICmi kt ILi lc thp vi 1 3 R a l,
IL-13, cng vi 1NR4. ILIL-4Ra c th 13Ra
to thnh mt
ih th chiic
nng cho iL-13.
cng c coi
nh l inl protcin ph tr thay
i
i
vi
chui
gamma
th th cytokine
chung cho qu
trnh truyn tn
hiu 11,-4

H
th
th cytokine lp II

Siu
h
th
th
cytokine
to mu

Siu
h
th
th
cytokine
tao mu

270
CD 213
a2

C c t bo B.
bch cu n
nhn, nguyn
bo si, cc
t bo ni m

CDw
217

C c t bo T
ghi nh hot
ho

120

C D 2 39

C c t bo
hng cu

78

Th IL-13 nh
mt moncxiier lin
fc i lc cao \i ii>terteukin-13
( IL-13), nhung
khng lin k vi
ILr4; cc t bo
ngui biu hin Lr
13RA2 cho thy
lin k IL-13 c
hiuviiliiccao
Hom odim er th
th
interleukin
17

h
IL -1 3 R a Siu
Ih
2,
IL- th
cytokne
13BP
to mu

U1-17R,

C c th
lcTLA-8 th cy lo kine/ cht
ho
hiig
dng
Siu
ho
Proteiii
mng B -C A M
dng I. Khng (Phn t im n iiinguyn P8/G253 ct dnh noglobulin
ngi,
bo B),

B-CAM, l mt . 11.

glycoprotein b ihm
mt t bo c nu Lubiu hin vi mt her
kiu phn b hn

ch trong cc m
trng thnh v
bo

thai

bnh

thng v c
diu ho mnh

ln sau s bin
i c tnh trong
mt s' dng t
bo.

Cu

trc

lon th ca n
ging vi cu
trc ca du hiu
ung th ngi
MUC18 v phn

t kt dnh thn
kinh g SCI

271

C D 2 4 0 C c t bo
hng cu
CE

45.5

C D 2 4 0 C c t bo
hng cu
D

43,5

Nhm mu RhssiK. R H C E ,
khng nguyn Q fe . R H 30 A ,
C 6 tfi l ic phn IRHPI.
ca phic h ogome Rh4
c chc nng knh
hay xnchuyi trong
mng tTg cu. N
ctiiknuccaov
giisulicnglpkip
M

C D 241

C c t bo
hng cu

50

H Rh

______ ________

Nhm
mu
Rhesus. khng
nguyn D. C
th l mt phn
ciia phc h oligome c chc
rvng knh hay
vn
chuyn
trong
mng
hng
cu.
K hng c mt
kiu hnh khng
c R H D ngui
da trng_________

H Rh

Glyeoprotcin kt
hp nhm mu R H 5 0 A
Rhcsus RH50,
ihnh phn ca
phc h nhiu
di cm v

H Rh

khng

nguyn

RH. cn thit
cho
s vn
chuyn v s kt
hp phc h
mng Rh vi b
mt t bo hng
cu, c tnh
tng ng cao
vi RH, cc
thnh

phn

30kD.

Cc

272

khuyt tt
RhAg l nguyn
nhn ca bnh
thiu mu kinh
nin i km vi
stomatocytosis
v spherocytosis, lm gim
tnh thm lc, v
tng tnh thm
CD242 Cc t bo
hng cu

42

CD243 Cc t bo
ngun
/t
tin

170

CD244 Cc t bo
NK

66

Phn t kt dnh ICAM-4,

ni bo 4, nhm Lw
mu
LandSteiner-Wiener.
Cc phn t LW
c th gy ra tc
mch kt hp
vi au cp tnh
bnh hng cu
hnh li lim
Protein 1 IMDR-1.
khng a thuc 170
(Glycoprotein
P-gp s dng
ATP bcrm cc
thuc k nc ra
khi t bo, v
vy nng ni
bo v tnh c
ca chng tng
ln. Gen MDRl
c nhn trong
cc dng t' bo
khng a thuc.
2B4 l mt gly- Cu t
coprotein b mt gn cm
t bo c quan ng s
h vi CD2 v lot ho
trong iu ho 2B4, t
chc nng t bo bo NK
git t nhin v KNAIL),
t bo lympho

Siu h
immunoglobulin, phn
t
kt
dnh ni
bo
(ICams)
Siu h
ABC ca
cc protein vn
chuyn
lin kt
ATP

Siu
h
immunoglobulin

273
T. Chc nng s
cp ca 2B 4 l
iu chinh tcmg
tc th th-cu
t gn khc
tng cng hot
ho bach cu.
CD 245

C c t bo T

220 - 240 Protein tng tc NPAT

cy clin E /
Cdk2
p220. N P A T lin

quan n s kin

pha s cha kho

v lin kt
tnh kinaza
clinE/ Cdk2
hon vi

hot
cytun
qu

trnh phin m

gen histon ph
thuc sao chp.
Gen N P A T cn

thit cho s duy

tr t' bo v c
th l thnh vin
ca

thng

CD 246

c
biu
hin rut
non,
tinh
hon v no
nhng khng
biu hin
cc t bo
lym pho bnh
thng

cc gen

trc

(housekeeping
gene)___________
177 kDa; Kinaza
lympho A L K
sau khi ghp (t bo ln
ng CD30*), ng vai
ha to tr quan ng
mt giy- trong s pht trin
coprotein no, lin quan n
trng cc bnh Hodgkin
thnh
hay
Iym fio
200 kDa khng
phi
Hodgkin nt ghp
vi s hon v
t(2;5)(p23,q35)
hay inv2(23,q35).
S pht sinh ung
th nh chc nng
kinaza uc hoat

H
th
th insulin
ca
protein tyrozin
kinaza

274
ho bi s oligomer h a ca
N P M l-A L K u c
lm trung gian bi
p h n N t i
CD 247

C c t bo T.
NK

16

Th th t bo C h u i
T.
c vai tr
trong tp hp v
biu hin phc
h T C R cng
nh truyn tn
hiu nh vo s
khi ng khng
nguyn. T C R ^
cng
vi

|cD3Z

T C R a P v heterodimer yS v
CD 3- ,-S, v -8
to thnh ^ c
h
T C R -C D 3 .
Q iu i ng
mt vai tr quan
trng trong vic
nhn bit khng

nguyn cp i
vi mt vi con
ng truyn tn
hiu ni bo.
Biu hin thp
ca
khng
nguyn dn ti
p ng min
dch sai hng.

Siu
ho
im m unoglobulin

275

Ph lc II. Gii ngha danh t min dch.

ABO: Cc khng nguyn ca h thng nhm mu ABO c

bc l trn b mt mng hng cu ,chng c s dng phn
loi cc nhm mu cho truyn mu. Nhng c th khng biu
hin cc khng nguyn A v B t bo hng cu s hnh thnh
cc khng th chVig li chng.
Accessory effector cells: C mt trong min dch tip thu
hoc min dch thch ng l nhng t bo tr th trong p ng
min dch nhng khng c kh nng nhn bit khng nguyn
c hiu. Chng bao gm cc t bo thc bo (phagocytes), t bo
Mast, v t bo NK.
AIDS: Hi chng suy gim min dch mc phi (Acquired immune deficiency syndrome), l mt bnh do nhim virus
HIV(Human immunodeficiency virus).
Acute Lym phoblastic leukenia: l mt bnh ung th mu
c tnh ca dng lympho khng bit ho bt ngun t nhng t
bo tu xng, c th lan truyn i vi c hai dng dng t bo
B v T. Hu nh t't c nhng bnh ung th bch cu ny u
biu hin ch yu dng t bo B c bit ho mt phn (k
hiu B-ALL) trong khi mt t l nh ca ung th c biu hin c
tnh ca dng t bo T (k hiu T-ALL).
A cquired im m unc response: p ng min dch tip thu
hoc p ng min dch thch ng. Vic tim chng vi mt loi
Vacxin hoc mt khng nguyn no c gi l gy min dch
ch ng, c th phn bit vi vic truyn mt khng th vo mt
c th cha gy min dch. Cch lm gi l gy min dch th
ng.
Acute-phase Proteins: l nhng protein c tm thy
trong mu ca mt c th b ly nhim vi khun xut hin trong
giai on sm ca bnh. Nhng protein ny tham gia bo v cho

276

vt ch chng li tc nhn nhim trng giai on u. V d

mt dng Lectin lin kt vi Mannose.
A daptor Proteins: L nhng protein thch ng quan trng
to s lin kt gia cc th th (receptor) v cc thnh vin ca
mu trn con ng truyn tn hiu.
Adenoids; l nhng m Lympho lin kt vi th nhy, nm
khoang nhy mi.
Adhesion molecules; Cc phn t kt dnh lm nhim v kt
dnh gia t bo ny vi t bo khc trong qu trnh hp tc t
bo. Chng bao gm cc Integrins, Selectins, cc thnh vin ca
mt h gen ln Globulin min dch,...Chng tham gia hp tc
trong p ng min dch.
Adjuvant: T cht l mt cht bt k no c kh nng lm
tng cng p ng min dch vi mt khng nguyn c
gy min dch. Ngi ta thng trn t cht vi khng nguyn
gy min dch c hiu qu.
Adoptive im m unity: L tnh min dch chp nhn c c
nhng c th nhn cha bit p ng min dch hoc b chiu x.
c tnh min dch ny c to ra bng cch truyn cc t bo
Lympho ca nhng c th cho gy min dch
A fferent lym phatic vessels: Mch dn lympho tr li ca
mt hch bch huyt. Cc i thc bo v cc t bo c tua t
nhng v tr nhim ca cc b phn c th c th tr v hch
bch huyt theo ng dn ny.
Afinity: i lc, kh nng hp dn v lin kt ca phn t ny
vi phn t khc mt v tr nht nh trn phn t. V d
s lin kt ca mnh Fab ca phn t khng th vi mt khng
nguyn (xem thm thut ng Avidity).
A ffin ity chrom atography; sc k i lc, mt kiu sc k
tinh ch mt cht da vo i lc ho hc ca n vi mt cht
khc c lm bt ng trn mt gi th rn. V d mt khng
nguyn c th c tinh ch bng sc k i lc trn mt ct c
cha mt cht gi th gn vi cc phn t khng th c hiu vi
n.
Agammaglobulinemia; Bnh thiu ht gammaglobulin
trong huyt thanh. Bnh ny l do nguyn nhn r lon di
truyn trong dng t bo B ch pht trin giai on tin R
(pre-B), khng pht trin thnh B trng thnh. Bnh ny l do
thiu ht v gen m ho cho mt Protein Tyrosin Kinasc' f)fk.

277

Agglutnation: S ngng kt hin tng thng xy ra khi c

cc phn t khng th lin kt vi cc phn t khng nguyn
trn b mt ca cc ht cc tiu th hoc t bo st cnh nhau.
V d cc phn t lectin khi lin kt vi mt s phn t Glycoprotein trn mng hng cu c th gy ngng kt hng cu.
Agonist peptides: L nhng khng nguyn peptide gy hot
ho nhng t bo T c hiu tit ra cytokinee v sinh sn cn gi
l cc peptide ng vn. Tri li, Antagonist peptides i nhng
peptides i khng, gy tc dng ngc li.
Alleles: Alen l dng biu hin khc ca mt locus gen.
Allergens: L nhng khng nguyn gy ra hin tng qu
mn hoc cc phn ng d ng. C th gi l khng nguyn gy
d ng, hay cn gi l d nguyn.
A lle rgic reaction: Phn ng d ng p ng li vi cc tc
nhn khng c ca mi trng hoc cc khng nguyn gy d
ng. Phn ng ny l do nhng khng th hoc do cc t bo T
khi thu tn ti t trc. C nhiu c ch min dch khc
nhau ca phn ng d ng nhng biu hin chung nht l s lin
kt ca Allergens vi khng th IgE nm trn t bo Mast gy ra
hin tng hen suyn, st, nn ma, ngt mi, sc phn v v c
th t vong (qu mn typ I).
Allergy: Hi chng d ng i vi khng nguyn khng c
ca mi trng.
Alloantigens: D khng nguyn, c th nh ngha nh l
biu hin a hnh mc cc locus MHC. Chng kch thch s
thi b m ghp d gen mnh m.
A llograt; Ghp m t bo d gen
Allotypes: Kiu a hnh alen c th c pht hin bng cch
s dng khng th c hiu i vi cc sn phm gen a hnh.
Trong min dch hc, nhng s khc nhau allotypes cc phn
t immunoglobulin rt quan trng vi s gii m di truyn
ca cc khng th.
Altered peptide ligand: Cu t gn peptide bin i, c th
l mt cht c cu trc ging mt phn cht ng vn Agonist ,
hoc mt peptide thng lin quan cht ch vi ch*t ng vn v
trnh t axit amin. iu ch gy ra s p ng mt phn ca
t bo T i vi peptide ng vn.
A lternative pathway: Con ng hot ho b th bn cnh
khc con ng hot ho c in (classical pathvvay). Con ng
ny dc khi u t protein b th C3b lin kt vi b mt ca

278

tc nhn gy bnh. Do , con ng hot ho b th ny c c

im min dch bm sinh(innate immunity).
A naphylactic shock: Sc phn v (lin quan n bnh qu
mn typ I c s tham gia ca IgE).
Anaphylatoxins ; L cc mnh peptit nh ca cc protein b
th b phn hu v c gii phng ra trong qu trnh hot ho
b th (c th c gi l cht phn v). Cc mnh peptit ny
c th th (receptor) c hiu nhn bit v c tc dng lm
huy ng cc t bo gy vim tp trung n v tr c mt cc cht
phn v ny. Cc mnh C5a, CSa. v C4a u l nhng anaphylatoxin.
Anchor residues: Cc gc rii neo l gc cc axt amin ca
mnh peptit khng nguyn dc ch bin v c lin kt vi
rnh lin kt peptit (groove) cc phn t MHC lp I c hiu.
Anergy: S mt ng, l mt trng thi khng c phn ng
vi mt khng nguyn. Ngi c trng thi mt ng l nhng c
th khng th c cc phn ng qu mn mun vi nhng
thch thc ca cc khng nguy n. Tng t, cc t bo T, B c
trng thi mt ng khi chng khng th p ng li i vi
nhng khng nguyn c hiu ca chng di nhng iu kin
kch thch ti u.
Antagonist peptides: Peptit i khng, l nhng peplit
thng c quan h rt cht ch v trnh t sp xp cc axit amin
vi cc peptit ng vn (agonist peptides).
Antibody: Khng th, l mt Icp globulin min dch c bn
cht glycoprotein kin kt c hiu ' i khng nguyn.
A ntibody com bining site: L v tr lin kt vi. khng
nguyn nm trn b mt phn t khiRg th.
A ntibody repertoire; Kho d t r khng th bao gm tng
th cc khng th trong c th ca mt khng th.

Antibody - dependent cell - mediated cytotoxicity

(ADCC): Kh nng gy c t bo q la trung gian t bo ph
thuc vo khng th, y l qu trnh tit cc t bo ch gn vi
khng th c thc hin bi cc t bf* git t nhin (NK) thng
qua s nhn bit ca th th Fc. Hu nh tt c cc ADCC u
c thc hin bi cc t bo NK thng qua th th Fc gamma
R III hoc CD16.
Antigen; Khng nguyn, l nhng phn t b't k c kh nng
lin kt c hiu vi khng th hoc vi th th khng nguyn.

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Nhn chung, cc khng nguyn khi xm nhp vo c th u c

kh nng lm sn sinh khng th. Tuy nhin, mt s khng
nguyn ch c c tnh lin kt vi khng th nhng khng lm
sn sinh khng th. Cc khng nguyn ny thng c phn t
rt nh c gi l Hapten cn phi lin kt vi mt loi protein
mang (carrier proiein) tr thnh mt immunogen c kh nng
sn sinh khng th.
A ntigen - capture assay: Xt nghim bt gi khng nguyn,
l mt k thut to ra s lin kt ca mt khng nguyn vi mt
khng th c hiu. Phc h ny c lin kt vi mt khng th
th hai c nh du enzyme hoc phng x sau thc hin
phn ng enzyme to mu c trng tip theo o mu hoc o
phng x pht hin khng nguyn. Xt nghim ny c thc
hin nh k thut ELISA hoc k thut RIA.
A ntigenic determ inant: Quyt nh khng nguyn, cn c
gi l epitop, l mt phn ca phn t khng nguyn lin kt c
hiu vi mt phn t khng th hoc vi th th khng nguyn.
Epitop ca mt phn t protein.
A ntigen receptors; Cc th th ca khng nguyn. l
nhng phn t protein nm trn b mt mng t bo T v t bo
B c kh nng nhn bit c hiu s trnh din khng nguyn.
M t qu trnh bc l mt peptit khng nguyn c ch bin
lin kt vi mt phc h ph hp m ch yu (MHC: Major
Histocompetibility) trn b mt mt t bo trnh din khng
nguyn (APC: Antigen pregenting Cell).
A ntigen Pregenting Cell: T bo trnh din khng nguyn
(APC) l nhng t bo ca h min dch bao gm ch yu l cc
t bo thc bo n nhn (Mononuclear phagocytes), cc i thc
bo (Marcophages), cc t bo c tua (dendritic cells v folicule
dendritic cells) t bo Langerhan ca da, v t bo B.
A ntigen Processing: S ch bin khng nguyn. Qu trnh
tiu ho cc prtin khng nguyn ngoi sinh bng cc protease
ca lyzosom v bng mng ca t bo sau khi nut khng
nguyn. Qu trnh ny cng c thc hin vi cc khng
nguyn virus nhim ni bo hoc vi cc khng nguyn ca
bn thn (autoantigen) nh tc dng ca mt c quan c bit l
proteasome ca t bo ch. Peptit khng nguyn sau khi c
oh bin s trnh din cho cc t bo T.CD4^ hoc T.CD8^.

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A nti-im m unogobulin antibody: Khng th khng li vng

khng bin i ca immunoglobulin dng pht hin cc phm
t khng th lin kt vi chng trong xt nghim min dch.
Antiserum (antisera): Khng huyt thanh (hoc cc khng
huyt thanh) l huyt thanh ca ng vt c gy min dch
khng li mt khng nguyn no . Trong huyt thanh c mt
tp hp bao gm nhiu khng th a dng (polyclonal antibodies), trng mi mt khng th lin kt vi mt epitop nht
nh ca mt khng nguyn. V vy mi mt khng th trong
khng huyt thanh u c mt cu trc ring b i t.
Apastic anemia; S thiu mu do khng pht trin dng t
bo ngun tu xng. Thiu mu do b hu hoi tu xng. C>
th iu tr bnh ny bng cy ghp tu xng
Apoptosis. Cht theo chdng trnh l mt hnh thc cht ca
t bo theo mt chng trnh c kch hot ni ti. c im
ca apoptosis l s phn hu nhn t bo v ngng t nhn
trong cc mnh nhn c bao bc bi cc bng mng cha c
t bo cht, sau c cc i thc bo tiu ho. Cc t bo
trong qu trnh tng sinh lun lun chu apoptosis l mt qui
lut t nhin ca s pht trin v cng din ra trong qu trnh
p ng min dch. Tri li, ci cht hoi t (necrosis) xy ra do
t bo b u c, b nhim c hoc thiu oxy. Hoi t li
mt s" lng rt ln cc mnh v t bo.
Appendix; Trong gii phu gi l rut tha, l mt m
lympho lin kt vi rut r gy ra hin tng vim rut tha.
A rthus reaction: Phn ng min dch do arthus tim ra. Phn
ng xy ra do khi tim mt khng nguyn l vo lp biu b. Khi
khng nguyn l s phn ng vi khng th ngoi bo gy ra
hot ho cc b th, t bo thc bo v hin tng p ng vim
ti ch.
Artefact: Vt lm gi, m hnh lm gi nhm minh ho mt
iu gi .
A topic allergy, atopy; C a, mt tnh trng nhy cm tng
ln vi s qu mn tc th, qua trung gian khng th IgE
Attenuated: Lm yu i mt tc nhn gy bnh, chng hn vi
khun gy bnh, virus bnh c lm yu tc dng gy bnh khi
c a vo c th vt ch gy ra p ng min dch nhiig
khng gy bnh lm sng nghim trng.
Autoantibodies: Cc t khng th l nhng khng th c
hiu chng li khng nguyn ca bn thn c th (autoantigen).

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Autog^rat: T ghp, s cy ghp ln mt khng th bng

chnh m t bo ca bn thn.
Autoim m une diseases: cc bnh t min, l nhng bnh
pht sinh do h min dch chng li bn thn.
Autoim m une hem olytic anemia; Bnh thiu mu do tan
mu t min, do t khng th lin kt vi khng nguyn trn b
mt hng cu to cli ph hu hng cu
Autoim m une response: p ng min dch, s p ng
min dch chng li cc khng nguyn ca bn thn, cng gi l
tnh t min (Autoimmunity).
Autoim m une throbocytopenic purpura: Bnh xut huyl
t min do thiu ht hng cu. Cc t khng th pht sinh trong
bnh nv lin kt vi cc tiu cu to ch ph hu tiu cu, lm
gim s lng tiu cu.
A vid ity; Ho tnh, l tng cc lc lin kt i lc ho hc gia
hai phn t hoc gia cc t bo vi cc t bo khc c nhiu v
tr lin kt.
A zathioprine: Mt loi thuc km hm min dch mnh c
kh nng dit cc t bo tng sinh nhanh. Cc t bo ny gm
cc t bo lympho gy ra p ng thi b m t bo cy ghp.
p sheet: L gp p, mt dng cu trc bc 2 c bn ca phn t
protein.
Bacteria: Vi khun, mt dng vi sinh vt nhn s (procariote)
bao gm nhiu loi v nhiu chng khc nhau. Vi khun c th
sng trn b mt t bo khong khng bn ngoi mt t bo vt
ch, trong cc bng mng (vesicles) hoc trong ch't dch t bo
(cytosol). Rt nhiu loi vi khun gy ra cc bnh truyn
nhim khc nhau.
Bare lym phocyte syndrome: Hi chng thiu ht nghim
trng dng t bo lympho, trong MHC lp II khng c biu
hin trn b mt t bo do thiu ht mt s gen diu ho khc
nhau. Bnh nhn mc bnh ny b thiu ht min dch c tnh
,ch c mt s t t bo TCD4^
Basophils; L dng t bo bch cu (Leucocyte) cha cc ht
nhum mu vi thuc nhum base, c chc nng gn giVig t
bo Mast. l t bo a kim.

B-cell antigen receptor hoc B - cell Receptor (BCR): Th

th ca t bo B l mt phn t immunoglobin xuyn qua mng

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(IgM v IgD hoc IgG) lin kt khng cng ho tr vi cc chvii

ga(CD79a) v IgP(CD79b).
p*cell corona: Vnh t bo B nm trong l lch (spleen) l
mt vng th t c mu trng kt hp s b vi cc t bo B.
p-cell mitogens: Cht kch thch s phn chia t bo B, lm
tng sinh t bo B.
Bool group antigens; Cc khng nguyn nhm mu.
Bone marrovv: Tu xng, l mt c quan lympho trung n,'
c chc nng to mu. sinh ra cc t bo mu khc nhau bao
gm hng cu, tiu cu. t bo mono. cc t bo bch cu nhn
a hnh (polymorphonuclcar leucocytes), cc t bo lympho (lym
phocytes). Tu xng cng l ni pht sinh v pht trin t bo
B ng vy c v v cng cha ng cc t bo ngun (stom
cells) sinh ra co dng t bo T kh tu. V vy, s cy ghp tu
xng c th sa cha c tt c thnh phn c bn ca t bo
mu, cn thit cho p ng min dch.
Booster im m unization: Gy min dch nhc li. Tim khng
nguyn gy min dch nhc li sau khi tim ln u lm tng
trng thi min dch
Bronchial-associated lym pho tisues: Hoc BALT. Nhng
m lympho lin kt vi ph quan. Nhng m ny rt quan trng
vi s p ng min dch vi cc khng nguvn l) ht vo v
i vi nhim trng h hp.
Bursa o f Pabricius: Ti Pabricius, mt c quan min dch
ca lp chim, l ni cn thit cho s pht trin ca t bo B cui
lp chim. Nu c quan ny b ct i chim non th s gy ra s
mt i cc t bo B chim trng thnh. Ngi ta khng tm
thy c quan tng ng ny ngi.
C l in h ib ito r; (Cl-INH), cht km hm Cl, l mt proloin cch s hot ho b th Cl, lm mt hot tnh enzyme ca phc
h C lr: Cls. Thiu ht Cl-INH l nguyn nhn ca bnh ph
mch di truyn.
C3/ C5 convertase: Enzyme lm bin i C3/ C5. S to ra
enzyme ny ti'n b mt tc nhn gy bnh hay trn t bo dch
cn ph hu l mt giai on quan trng ca con ng hot ho
b th. C3/ C5 convertase sau xc tc cho s loi b mt s' ln
cc phn t C3 trn b mt tc nhn gy bnh gip cho s
opsonin ho v to ra nt dy phn ng gy tn thnj mng l
bo tc nhn gy bnh (vi khun).

283
C 5 a r e c e p to r ; T h th ca b th C 5a, l m t th th c by
vn g xon xu yn qua m ng lin k t vi protein G h eterotrim e.

Calcineurin: L mt photphataza serin/ threonin ca t bo

(;ht ng v a i tr quan trng nhng cha c xc n h r trong
vic tru y n tn hiu qua th th T C R . Cc thuc km ch m in
doh n h cyclosporin A v FK 506 to ra cc phc h vi cc protein c a t bo gi l im m u n o p h ilin c tc dng lin kt v gy
b t h o t calcin eu rin s lm km c h p n g m in dch ca t
bo T.
C a ln e x in : L m t protein 8 8 kD a c tm th y li ni ch t
(ER: E n dop lasm ic R eticulum ) c kh n n g lin k t vi cc th n h
vin p rotein c gp np m t phn thuc si u h globu lin m in

dch v gi cho cc protein nv li trong li ni cht cho n

k h i ch n g c gp np hon lon, cn gi l protein "bo m u .

Capture assay: Xt nghim bt gi min dch.

C a r r ie r : C ht m ang c bn ch t protein l, lin k t vi m t
k h n g n gu yn phn t nh khng c kh n n g p ng m in
dch (khng sin h m in dch). D ng kh n g nguyn n y c gi l
h a p ten . In vivo, cc protein ca bn th n c th c n g c th c
dn g lm cht m ang nu chng c ci bin n g bng mt
hapten. i u n y quan trng trong h in tng d ng vi thuc.

Caseation Necrosis: Hoi t trong li, mt dng hoi t c

thy gia cc khi u ht trong bnh lao phi. Ngi ta thy
xut h i n cc v n g trn g nh phom at gia m hoi t.

CD: Cm bit ho (Cluster of Differentiation).

C D 4 5 : L mt cm bit ho kh n g nguyn chung cho cc bch
cu c bn cht l mt tyro zin photphataza bc l nhng dng
ng p h n kh c nhau trn b mt cc lym pho T k h c nhau. Cc
dng ng phn ny ni chung biu th mt chc nng nh CD
45R do m t exon m ho c m t k iu lin k t n h t n h vi mt
k h n g th c hiu.

CDR; Vng xc nh b sung (Complementarity determining

regions).
C D R l , C D R 2 , C D R 3 : L ba vng xc n h tn h b sung ti
v t r tn cng ca k h u vc biVi i (V .D o m ain) trn cc phn
t k h n g th hoc trn cc T C R . Ba v n g n y to nn cc thng
lng (loop) tip xc trc tip vi kh n g nguyn hoc peptit.

284

Cell adhention molecules; Cc phn t kt dnh t bo, gi

tt l CAM. l nhng protein b mt t bo, to ra s lin kt
gia cc t bo vi nhau trong cc m.

Cell-mediated iininunity hoc Cell-mediated immune

r e s p o n s e : T n h m in dch tru n g gian qua t bo hoc s p
ng m in dch qua tru n g gian t bo. M t s p n g m in
dch thch ng trong khng nguyn c h iu vi t bo T ng
v a i tr ch yu. p ng m in dch n y bao gm tt c tn h min
dch th ch ng nhng khng bao gm qu trn h tit kh n g th.

Cell-surface Immunoglobulin: Globulin min dch trn b

m t t bo. l th th t bo B (BCR).
C e llu la r I m m u n o lo g y : M n hc m in dch ch u y n n gh in
cu tn h m in dch trn c s t bo.

Central lymphoid organs; Cc c quan lympho trung ng

l nhng v t r pht trin ca cc t bo lym pho ngvi, tuyn
c, (thym us) l nhng c quan lym pho tru n g ng.
C e n t r a l t o le r a n c e : S du n g np mc tru n g ng. S
d u ng np c th i t lp trong qu trn h p h t tri n ca cc t bo
lym pho cc c quan lym pho tru n g ng kh c vi d u n g np
mc ngoi v i (p e rip h e ral tolerance).
C e n t r o b a s t s : N guyn bo tru n g tm. l nhng t bo c
k ch thc ln ang phn chia nhanh, c tm th y cc tru n g
tm m m , c n g l nh ng t bo t b in som a mc cao.
C c t bo B ghi nh v cc t bo tit k h n g th u bt ngun
t cc t bo ny.

Centrocyte; T bo trung tm. L cc t bo nh khng chia

tru n g tm m m bt ngun t n gu yn bo tru n g tm . C hng c
Ih ch n (trng th n h ) thn h cc t bo p lasm a tit k h n g th
hoc tr th n h t bo ghi nh, hoc c th cht theo chng trn h
(apoptosis). i u n y p h thuc vo s tng tc gia th th
ca ch n g vi k h n g nguyn.

Chedak - Higashi Syndrome; L mt hi chng thiu ht

chc n n g ca t bo thc bo, cha r nguyn nhn, nh ng
t bo ny, lysosom e m t k h nng dung hp vi cc th th n
bo(p hagosom e) v kh n n g g it vi k h u n ca nh ng t bo
thc bo n y b su y gim .

Chemokines: L cc xitokin c phn t nh gip cho s di

ng v h o t ho t bo, c b it l cc thc bo v cc t bo
lym pho. C h n g c v a i tr quan trng trong p ng vim .

285
C h r o n ic g r a n u l o m a t o u s d is e a s e : B nh u h t m n (u h t
m n tn h ). l b n h th iu h t m in dch, trong c n h iu u
h t h n h th n h do vic loi tr khng y ca cc t bo thc
bo. Bnh do thiu h t h tliVig cnzym e N A D P -H oxidase dng
to ra gc sup e ro xit tham gia dit vi kh un.

ClassII - associaed invariant Chain, CLIP: Peptit lin kt

vi phc h ph hp m ch yu lp II ti rnh lin k t ca
M H C lp I I sau k h i b ct gt bng cc protease. Peptit ny
sa u c ly khi rnh lin kt nh protein HLA - DM trong
c ch lin kt vi m nh poptit. khng nguyn s c trn h din
cho lym pho T C D 4 .

Class svvitching: Xem isotyi^e svvitching.

C la ss; X em isotype.
C la s s ic a l p a th v v a y : Con ng hot ho b th kinh in
c bt d u nh k h n g ih lin kt vi k h n g n gu yn , tip theo
cc th n h phn b th C l, C4. C2 c bin i to C 3 / C 5
convertase (xem thm a lte rn a tiv e pathvvay).

Cional deletion: S loi b dng, s loi b nc t bo lympho cha c h n bng cch lin kt vi cc t k h n g nguyn(auto
antigen). Lo i b dng l mt c ch' ch yu ca s dung np
tru ng ong v cng x y ra s dung np ngoi vi.

Clonal expansion: S lan truyn dng. l s tng sinh

ca dng t bo lym p h o c hiu vi m t k h n g n gu yn kch
thch. Q u Lrnh trn xy ra trc kh i (; s bit ha thn h t bo
hiu qu. l g iai on c bn ca dp ng m in dch thch
ng cho php cc qu trn h c hiu kh n g nguyn tng s lng
chin u c hiu qu vi tc nhn gy bnh.
C lo n a l s e l e c t i o n t h e o r y ; L th u y t la chn dng. L l
th u y t tru n g tm ca m in dch thch ng trong s p ng
m in dch thch ng bt ngun t cc t bo lym pho rin g bit
ctc hiu k h n g nguyn. N hng t bo n y tng sin h p ng l i
kh n g nguyn v bit ho thnh cc t bo h i u qu c hiu
khng nguyn loi b tc nhn gy bnh v to ra cc t bo
thi nh (m em ory cells) lm bn vng tn h m in dch. L thuyt

ny c Niels Jerne v David Talmage nu ra u tin, sau

c M acrlan e B u rn et hon thin.
C lo n e : M t qun th t bo bt ngun t m t t bo t tin .

Cloned T- cell line: Tco mt dng t bo T hay clon mt dng

T. N ui cy tip tc dng t bo T bt ngu n t m t t bo t

286
tin. Dng t bo T clon cn p h i c k ch th ch thng
xu yn b n g m t k h n g ngu yn duy tr s t n g tr n g ca
chng. D n g T clon s c d ng tron g n g h in cu tn h c
h iu, s t n g trng v cc chc n n g gy h i u qu c a chng.
C lo n t y p ic : M t k iu clon, ni ln c im duy nh"t ca m t
dng t bo ri n g bit. V vy, mt k h n g th n dng (monoclon al antibody) p h n ng vi m t th th b m t dng T ny
l k h n g th n h n bit c hiu k i u clon T.

Clusters of Diffentiation (CD): Cm bit ho khig

n gu yn . L n h n g phn t bc l trn b m t t bo, c n h n
b it bi n h n g k h n g th n dng c h i u vi ch n g. S lng
CD h in nay ca cc t bo h m in dch c tm ra ln
n h n g trm loi (C D 1-C D 247).
C o -d o m in a n t: n g tri. M t gen c biu h i n kh i c h ai

alen ca mt locus u c biu h in nh n h au trong cc d hp

t. H u nh tt c cc gen c c tn h n y bao gm cc gen c

tnh a hnh cao ca phc h ph hp m ch yu (MHC).

C o d in g jo in t: on n m , ch ni m c to th n h bn g

cch ni khng ch n h xc ca m nh gen V vi mt m nh gen J

(hoc D) trong p hn t globulin m in dch (Im m un o globin) hoc
ca cc gen m ho cho th th ca t bo T.
C o - is o g e n ic : Xem congenic.
C o lle c t in s : L m t h cc lectin lin k t vi ng ph thuc

canxi, hoc l nhng lectin cha cc trnh t ging collagen. Cc

protein li n k t vi m an n ose c n g l cc collectin .
C o m b in a t o r ia l d iv e r s it y : S a d n g do t hp. Cc th th
m in dch b iu h in hai k iu a d n g do t hp c p h n b it vi
nh au. S a d n g do t hp sin h ral do s k t hp cc n v

thng tin di tru yn tch bit. C c m nh gen ca th th ni vi

n h au th eo n h iu cch t hp k h c n h au t o nn cc ch u i th th
khc n h au , sau h ai chui th th (chui n n g v ch u i nh
ca Ig, chui v p hoc y v c a TCR) s k t hp vi n h a u to
ra v tr n h n b it k h n g ngu yn .
Common lyphoid progenitors: cc t tin ch u n g c a t bo
lym pho. l cc t bo ngun sin h ra tt c cc t bo lym pho.

287
C hng b t du t cc t bo ngun to m u a n n g (p lu rip oten t
h em a to p oietic stem cclls),
C o m m o n v a r ia b le I m m u n o d e lc ie n c y : S th iu h t m in
dch bin d n g chun g, ] s thiu h t ch u n g trong vic s n
xu t cc k h n g th. trong nguyn nhn pht sin h bnh cha
r. C s lin quan rt m nh m vi s xc lp bn gen ca
phc h M HC.
C o m p e t it iv e b i n d i n g a s s a y s : Cc xt nghim lin k t cnh
tran h, l nhng xt nghim huyt than h hc trong nhng

khng nguyn cha bit s dc pht hin v nh lng nl

k h i n n g k m h m s li n k l c a c h n g l vi m t c u t g n

(lig an d) nh d\i d bit vi mt khng th c hiu vi chng.

(/O m p le m e n t: B th. I. nhng i)rotein h u y t tng phn
ng vi nhau nhm tn cng cc dng tc nhn gy bnh ngoi
bo. I3 th c th c hot ho t )ht di vi m t s tc nh n
gy bnh (con ng hot ho bn cnh bt u t C3b) hoc do
kh n g th li n kt VI tc n li n gy bnh (con ng hot ho
k in h in bt u t C l) . H iu qu ca cc con ng hot ho
b ih l to ra phc h tn cng mng (M A C ) v opsonin ho tc
nhn gy bnh to iu kin d dng cho cc thc bo tiu dit
tc nh n gy bnh.
C o m p le m e n t R e c e p t o r s (CR): Cc th th ca b th. L
n h ng p rotein trn b m t m ng t bo lin k t vi cc b th
Kn vi cc tc n h n gy bnh. Cc th th ca b th cc thc
bo (p h agocytes) cho plip ch n g nhn bit tc n h n gy bnh v
ph hu chng.
C o m p le m e n t a r it y d e t e r m i n i n g r e g i o n s (C D R s): Cc v n g
xo nh b sung. L mt phn phn t th th tip xc vi cu
t (lig an d) c h i u v xc nh tnh dc h iu ca chng. C D R s
l phn d bin i nht ca protein t th, to cho cc th th
tn h a dng cu trc. V n g ny bao gm su vng thng lng
(loops) u tn c n g xa ca cc khu vc (dom ain) d b in i
ca th th, ba vng thng lng l hai dom ain ca th th.
C o n f o r m a t io n a l e p i t o p e s , d i s c o n t i n u o u s e p it o p e s : Cc
(uy nh k h n g n g u y n khng gian hoc gin on. Cc ep ito p es
ny dc h n h th n h t int s vn g lch b it tron g trn h t cu
trc bc n h t ca m t phn t protein k h n g n gu yn gp li
tron g kh ng gian. Cc phn t kh ng th ch lin k t vi n h n g

288
epitopes khng gian cc khng nguyn t n h in khng b b i n
tnh.
C o n g e n ic s t r a in s : Cc ch n g chut n h t giVig n h au v di
tru yn t t c cc locus nhng ch khc n h au m t locu s. M i
chng n y c to ra bng lai cho lp l i gia cc chut m an g
c im m ong m un tp tru n g vo m t ni ch u t c u n g cp f
s di truyn cho mt b su tp cc ni congenic.
C o n s t a n t r e g io n s ; Cc vng khng bin i. v n g h n g nh.
C o n t a c t h y p e r s e n s it i v i t y : Qu m n tip xc. L m t d n g
qu m n m un, trong cc t bo T p n g li cc khnK
n gu yn gy di n g khi tip xc vi da. V d: M t c h t c per.itad eca-catecol l cy leo Ivy (cy thng xun ) kh i tip xc vi
da s gy h in tng qu m n tip xc.

Continuous epiopes hoc inear epitopes: Cc quyt nh

khng nguyn lin tc hoc cc quyt nh khng .nguyn thtiS
bao gm trnh t lin tip cc gc acid- amin ca mt epitopes.
C o n v e r t a s e : H ot tn h en zym e lm bin i p rotein b th>
th n h dng c hot tnh. Vic to ra C 3/ C 5 convertase l mt si
k in quan trng n h t trong h ot ho b th.
C o o m b te s t; X t nghim coomb. L x t n gh im k h n g th lim
k t vi t bo h n g cu. H ng cu kh i c bao bc b n g c.c
k h n g th . s b ng ng k t nu ch n g bc l i vi m t khig
th k h n g li Ig. X t ngh im coomb kh quan trng p h t hiin
cc k h n g th k h n g ng ng k t chng li cc t bo h n g cu (ic
s n x u t c m t k h n g ngu yn RH k h n g ph hp tron g khi ci
th ai.
c - R e a c t i v e p r o te in : P rotein phn ng c , m t d n g proteiin
ca pha cp tn h lin k t vi phthorylcholin, tron g phot ph orylch olin l th n h phn c - p olysaccharid e c a vi khuin
Strep tococcu s p n eu m on iea. N h iu loi vi k h u n c n g c p h o tphorylcholin trn b m t t bo c th k t hp vi p rotein phin
n g c . V v y c - reactive protein c th lin k t vi n h iu loi v i
k h u n to iu k in opsonin ho hp n cc thc bo. ProLoiin
k h n g th lin k t vi cc m ca ng v t c v.
C r o s s - m a t c h in g : m t xt nghim phn loi nh m m u V

xt nghim tnh ph hp m c dng trong truyn mu V

tron g cy ghp m t bo.

Cross - reaction; Phn ng cho. Phn ng lin kt gia mit

khng th v mt khng nguyn khng gy p ng tng hP

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k h n g th d. Do (l. nu m l kh ng ih k h n g li k h n g ngu yn

A. cng lin kt VI khng nguyn 13, ngi ta ni rng khng

tho n y p h n ng' cho vi khn n gu yn B.
C u t a n e o u s ly m p h o id a n t ig e n ; K hng ngu yn lym pho (CLA)
ca da l m t phn t tham ^ia vo (lAn dat t bo lym pho quay
tr li da ca ngi.
C u t a n e o u s T- C e ll ly n ip h o m a : u lym pho ca t bo T da,
s siiih trn> c tnh ca cc t l)o T da.
C y c lo p h o s p h a n iid e : Thuc km hm m in dch c bn cht

l tc nhn alkyl ho c Lc (lng dit nhanh chng cc t bo

(lang p hn chia, bao gm c cc t bo lym pho tng sin h dp ng
VI khng nguyn.
C y c l o s p o r i n A: Thuc km hm m in dch m nh, km hm s
Iruyn tn Inu t cc TCR, ngn ci hot lio t bo T v chc
Ii n ^ gy hiu f|u;i. Thuc ny lc dng vi C y clo p h ilin lo ra
phc h gy b l hoi phcspliotase sorin/ treonin ca lcin e u rin .
C y t o k in e e s : P roteiii li l ('a cc l bo gy tc ng vo cc
t bo khc. X ito k in dc t bo lym pho tit ra c gi l lymhok in hoc in te rleu k in (vit l t l IL), X itokin tc dng ln cc
t.h th dc hiu VI xitokin c ml t bo m chng nhm ch.
C y t o k in e r e c e p to r s : Cc th tl! n h n b it xitokin. S lin
k t Ra th tl v xito k in to ra cc hot dng mi trong t bo
nh; t n g triig , bit lio, hoc cht.
C y t o t o x i c T c e lls : ('c' l bo T gy c. L nh ng t bo clil
c c t b o k h c . T t c cc t b o T g y c u l c c T- C D 8 cli
n h n bit M HC - lp I. Iihiig t bo TCD4 cng c th dit cc
t bo kh c d m t s tn n g hp. Cc t bo T gy c c vai tr
(]uan trng trong vic bio v vt ch chng l i cc c n li n gy
c ni bo.
C y t o t o x in s : Cc ch t c d vi t bo, l n h ng )rotein do
t bo T c ti t ra d ph huv l bo dch (nh im tr n g hoc:
bin d n g b t thng). Perforin, gran/.ym o hoc p ram en tin t
n h n g c tt bo c xc nh.
D e f e c t i v e e n d o g e n o u s r e t r o v ir u s e s ; L nh ng phn genom
ca re tro v iru s ci v genom ca t bo vt ch v hot ng nh

cc gen ca VI chv. C rt nhiu nhng b phn gon ca retrov iru s c ci Lrong genom ca chuL nht.

Delayed - type hypersensitivity: Qu mn mun. L ml

dng m in dch qua tru n gian t bo do mt kh n g nguyn l
tiep xc vi da, lm huy dng cc t bo T- C D 4 gy ra hin

290
tng vim . c gi l qu m n m un l do phn n g din b i n
t h n g gi n h n g ngy sau khi tim k h n g n gu yn dii da.
phn b it vi cc qu m n tc th (im m ed iate h y p e r se n sitiv ity )
trong p h n ng di da tn h theo p h t n gay sa u kh i tirn
k h n g n gu yn di da.
D e n d r i t i c c e lls : T bo c tua, cng c gi l cc t bo li
x th u (in te rd ig ita tin g reticu lar cells). l tm thV trong k h u
vc t bo T ca cc m lym pho. C hng l n h n g t bo c tirii
n n g kch thch m nh n h t cc p ng m in dch ca t bo T .
Cc m k h n g phi lym pho cng cha cc t bo d en d ritic n h n g
dng nh k h n g c kh n n g kch thch p n g t bo T trc
khi ch n g c h ot ho v di ch u yn n cc m lym pho. T b o
c tua bt ngun t t bo tin thn tu xng, c n p h n bi*t
vi t bo n an g c tu a (follicuIar dend ritic cell) l loi c chc
n n g trn h d in k h n g n gu yn cho t bo B.

Dendritic epidermal cells (dEC). T bo tua biu b. L

m t lp t bo ch u y n b it ca t bo Ty, , tm th y da (;.a
ch u t n h t v m t s loi ng vt khc, k h n g c ngi. Tt, c
cc CEC u c th th T dn g y. (y TCR).
D e s e n s it i z a t i o n ; Lm m t tnh nh y cm . M t phng ph.p

hay to cho cc th hay b d ng biu hin liu lng cht gy dli

n g t n g ln hy vng km hm phn n g d n g c a chng.
iu ny c th cho vic chuyn i cc k iu t boT -C D 4 v ciO
l b in i tn g hp k h n g th IgG th ay cho IgE.

D. gene segments, diversity gene segments: Cc mnh

gen to a dng. L cc trn h t ngn A D N ni cc m nh gen V
v J tron g cc gen chui n n g ca Ig v cc g en chui p v o.a

TCR trong qu Irnh pht sinh soma cua int exon vng bin clu
Diacylglycerol (DAG): Diaxylglyxerol l mt sn phm phin
hu ca lipit c gii phng ph bin t phospholipit inosital
nh tc ng ca p h osp h olip ase C-y. Vic s n xut DAG do plin
ng tip n h n ni ghp ca nh iu th th k ch th ch to ra. (/ic
DAG tip theo s h ot ho protein k in a se c tron g t bo v SI
tru yn tn h iu xa hn.
D ia p e d e s is ; S di ch u yn ca cc t bo m u , c b it l bclh
cu t th n h m ch m u n cc m t bo.

Differential Signaling Hypothesis: Gi thuyt truyn tin

h iu b it ho. G ii th ch con ng khc b it gi a cc qu trinlh
la chn m tn h v dng tnh (n egative, p o sitiv e selectiom )
tron g qu trnh chn ca t bo T lu y n th y m u s.

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D i f f e r e n t i a l a n t ig e n s ; Cc kh n g n gu yn bit ho, c p h t
h in m t s' t bo nh cc k h n g th c h iu. N h i u k h n g
n g u y n b it ho c vai tr quan trng c trng cho cc ph en otyp

bit ho ca t bo m chng bc l, chng hn nh cc Ig b

m t ca t bo B.

DiGeorge Syntrome: Hi chng DiGeorge, mt bnh thiu

h t di tru y n th e o gen ln, dng nh biu h in s th iu h t
p h t trin cc ch m t bo th n kin h quan trng. H u qu bnh
cn l s th i u h t tru yn hoocm on parathyroid dn n m t
k h n n g p h t tri n biu m tu y n thym u s.
D i r e c t c o o m b s te s t: X t ngh im (test) coomb trc tip, s
d n g a n ti-Ig t o n g n g k t cc t bo hn g cu n h m p h t h in
cc t k h n g th bao quanh t bo hng cu trong b nh t m in
hoc p n g m in dch k h n g thai nhi ngi m (xem in d irect
coom bs test).

Discontinous epitopes; Cc quyt nh khng nguyn gin

on (xem com form ation al epitopes).
A D N - d e p e n d e n t p r o t e i n k in a s e : P rotein kinase ph thuc
A D N , c m t tiu n v xc tc (c hot tn h en zym e) ng vai
tr q u an trn g tron g ti t hp cc m nh gen V D J. t b in lm

thiu yu t ny s a n phenotyp thiu ht min dch t hp

c tn h hoc b n h Scid (S everere C om bined Im m u n od ecien cy).
D o u b le - n e g a t i v e t h y m o c y t e s : Cc t bo c m tnh kp,
l n h n g t bo T ch a ch n (cha trng thn h) bn trong tu yn
c k h n g biu h i n c hai loi ng th th CD4 v C D 8 . V ic
bc l chn lc ch n g d in ra so n g son g vi s p h t trin ca t
bo T. C 4 q u n th t bo T ch yu bn trong tu y n c l:
qun th e m tn h kp, qun th dng tn h kp, qun th ch
cha m t loi C D 4 v qun th ch cha m t loi C D 8 .

Double positive thymocytes: Cc t bo c dng tnh kp.

L qun th t bo T nm tron g tu yn c u bc l c h ai loi t
bo l CD4 v C D 8 .

Early induced responses or early non adaptive res p o n s e s : Cc p ng c to ra sm , l m t lot p h n n g bo

v ca v t ch tron g giai on u ca n h im trng. C h n g
phn b it vi m in dch bm sin h (in n ate im m u n ity) v c c pha
cm n g v p h n b it vi m in dch thch n g (ad ap tive im m unity) v k h n g xy ra theo c c h chn lc dng cc t bo lym pho c h iu vi k h n g n gu yn .
E a r ly P r o B c e ll: xem P rotein-B -cell.

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E f f e c t o r c e lls : Cc t bo h iu qu, l cc t bo lym pho c
th to qu trn h ho gii tru n g gian lo i b t c n h n g y
bnh ra khi cd th. Cc t bo ny kh ng cn b i t ho xa hn.
tron g k h i n h n g t bo ghi nh cn ph i c b i t h o v p h n
chia trc k h i tr thnh cc t bo hiu qu. C c t bo lym pho
h iu qu cn c gi l cc t bo h iu qu c v tra n g .
E f f e c t o r m e c h a n is m : C c h h iu qu, c s d n g loi
b cc tc n h n gy bnh thc h in trong p n g m in dch bm
sin h v p ng thch ng.
Efferent lymphatic vessel: M ch bch h u y t i ra, ng ra
ca cc t bo lym pho ri khi hch bch h u y t i vo h tu n
hon.
E L IS A : xt ngh im h"p ph m in dch li n k t en zy m (xem
en zy m e-lik ed Im m uno Sorbent A assay).
E L I S P O T a s s a y : X t nghim ELISA ci b in , trong cc t
bo c t ln trn cc k h n g th hoc k h n g n g u y n gn
ln b m t ca m t gi th nha cm by p h t h in cc s n
phm chn lc ca t bo. Cc s n phm b y c sa u p h i
h in b n g m t k h n g th gn vi m t en zym c th p h n h u
m t c c h t to m u to -a v t c m u khi th m c c h t ca enzym e.
E m b r io n ic S t e m C e lls (E S c e lls ) : Cc t bo phi gc, cc t
bo phi ngu n. l nh ng t bo ang p h t tri n lin tc c
kh n n g b it ho th n h t t c cc dng t bo k h c. Cc t bo
ES c th c s d ng trong thao tc di tru y n , n u i cy m,
sa u c ci t thn h cc bng phi n g u y n b o (b la sto c y sts)
d n g d to cc dng t bin chut nht. Cc g e n tron g t bo
ES c loi b b n g k th u t ti t hp c n g n g u n ( hoc t i l
hp gen tng ng: hom ologous recom b in ation ), sa u t bo
ES c d n g to ra dng ch u t c gen k n ock -ou t.
E n c a p s u l a t e d b a c t e r ia : Vi k h u n c v bao b n g m t lp o
cacb ohydrat dy nh m bo v cho ch n g k h i b th c bo. Vi
k h u n c v bao ny c th gy ra n h im tr n g n goi bo. N cli
b th c bo v b ph h y b n g cc i thc bo k h i lp v ny
c lin k t vi k h n g th v b th c to ra c th b
nh im .

Endogenous pyrogens; Cht gy st ni sinh l nhng cytok in e c kh n n g lm t n g n h it c th. N c p h n b it vi

cc ch t en d otoxin ngoi lai ca cc vi k h u n gram m c n g gy

293
ra hin tng SL ('hnh nhnf (ndotoxin vi k h u n ny cng
khi dng co pyio^^Mi ni siiih .
E n d o t o x in ; L
ni (lc t vi khuan rhi ic giii )hiij ra

khi t bo VI khun 1) chL Iront c th b nhim bnh, tri vi

ngoi c t (exotoxin ) dc vi k h un tit ra khi cli n g cn sng.
Mt ni c t (uan ti-n< nht ca vi k h un gram Am l
lip o p o lysacch arid c ( L I S) c lc dnf r m nh gy tnp h) cytokino v gy ra hin ing sc ni dc t.
E n h a n c e r s ; L Iihn< ti nh t (lc hiu nm trong A D N gonom c tc d n g hot ha s |)hin m (transcrtion).
E L IS A : X t n gh im miM dch hp ph lin kt en zym , l k
thut dc s dn g ru ri ti-ong sinh hc, y hc cng nh min
(lch hc.
E o s i n o p h il s : L nhiig t bo bch cu a axit c tc d n g
bo v ch n g li nhim bnh k sin h trng. Cc t bo ny c
liot ha b n g cc t bo lym ])ho trong p ng m in dch thch
ng. B n h th n g m t t bo a axit trong m u rt thp
nhng s c tn g ln rt cao trong trng hp b d ng hoc b
nhim trng.
E o t a x i n 1 , E o t a x i n 2: l cc chem okin, cc ch t ti t c bn
ch t ha hc tc ng c h iu ln bch cu a axit.
E p it o p e ; Q u y t nh k h n g n gu yn l m t triih t cu trc
nm trn p h n t kh n g nRuyn dc nhn bit bi cc k h n
th hoc cc th th ca k h n g nguyn. Mt Epitoj)e ca t bo
T l m t trn h t p ep tit ngn t mt kh ng ngu yn c bn cht
])rot(*in c lin k t vi phn t MHC v c n h n b it bi mt
t bo T r in g bit. Cc epilox* ca t bo B l n h ng q u yt nh
khng n g u y n dc cc t bo H nhn bit. (,'c o))itope ny c
cu Irc g i n on, in hnh nha l c cu trc kh ng gian
Iiht nh.
Epitope spreading; S lan ta ep itop e c m t m t thc
t l cc p n g m in dch d vi cc t k h n g n g u y n (A utoanligon) c k h u y n h hng da dn g hn v dai dn g hn.
E p s t e i n - B a r r v ir u s (E B V ): L n h n g h erp e sv iru s gy
nhim chn lc ln cc t ho B ca ngi b n g cch lin kt vi
cc; th th c a b th (('R 2 hoc cn gi l C D 2 1 ). EBV thng
li n q u a n c h t c h v i b n h u n g t h v m h n g .

E q u i li b r i u m d ia ly s is : S thm tch cn bng, l m t k

th u t tron g cc k h n g th trong ti th m tch dc bc l ty
theo s Kng th a y i ca cc phn t k h n g n gu yn c th

294
k h u ch tn qua m n g thm tch. S lng ca k h n g n gu yn
bn trong v bn ngoi ca ti ti thi im trn g thi k h uch

tn cn bng s c xc nh theo s lung v i lc ca khng

th.
E -r o s e tt e s : P hn ng to hoa hng ca t bo ting cu cu.
P hn ng ny X3^ ra khi cc t bo T ca ngi c x l VI
cc t bo hn g cu cu. P hn ng to hoa hng vi hng cu cu
th n g d n g tch t bo lym pho T ca ngi.
E rp 5 7 ; L phn t bo m u tham gia vo qu trn h gn m nh
p ep tit k h n g n gu yn ln trn phn t M HC lp I li ni cht.
E r y t h r o b l a s t o s i s e t a lis : Bnh tan m u ngu yn bo hnf
cu c tn h , l m t dng bnh tan m u c tnh do Rh tron g do
k h n g th k h n g Rh ca ngi m xm nhp vo thai nhi lm
tan m u di dng nguyn bo hng cu (E ry th ro b la st) c th'
thai nhi.
E - s e le c t in : Xem se lec lin
E x p e r im e n t a l a l le r g i c e n c e p h a l o m y e l i t i s (E A E ): B nh
vim h th n g th n kinh trung ng thc ngh im , c to ra
sau kh i chut n h t c gy m in dch vi cc k h n g n gu yn
th n k in h c n g vi t cht m nh.
E x t r a v a s a t io n : L s di ng ca cc t bo hoc th dch t
cc m ao m ch m u n nh ng m xun g quanh.
F a b fr a g m e n t; M nh c t ca phn k h n g th lin k t vi
k h n g ngu yn , c to ra bn g cch x l k h n g th vi papain.
F (a b >2 : M nh k h n g th lin kt vi k h n g n gu yn khi x l
k h n g th vi tripxin.
F c fr a g m e n t: M nh kh n g th v n g kh ng bin i khi x
l k h n g th b n g papain.

Pactor B, factor D, factor H, factor I, factor P: L nhng

th n h p h n ca con ng hot ha b th bn cnh (a ltern a tiv e
p ath w ay). P actor B c vai tr l l ging vi vai tr ca C 2 b tron g
h ot ha c in, p^actor D l mt p rotease sorin gy ra phn h y
actor B. Pactor H l m t protein c ch c vai tr ging vi yu
t thc y p h n r. Pactor I l m t p rotease lm phn h y cc
th n h p h n khc n h au ca con ng h ot ha bn cnh. Factor
p gi l properdin l m t th n h phn iu ha dng tn h ca
con ng h ot ha bn cnh, lm n n h C3 co n v erta se trn b'
m t t bo vi k h u n ca con ng hot ha bn.
F a r in e r s iu n g ; L m t bnh qu m n do s tng tc ca cc
k h n g th IgG vi m t s' Ivng ln cc d n gu yn (allergen ) xm

295
nhp vo ng h h p v i vo th n h ca phi gy vim phi
v lm b in i trao i kh.
F a s; M t th n h vin ca h th th tip n h n T N F (Tum or
N ecrosis Factor). N c bc l trn m t s t bo to cho cc
t bo d n h y cm i vi nhng t bo bc l cu t F as tiu
d it ch n g.
F c r e c e p t o r s : Cc th th i vi m nh Fc. Cc th th n y
hao gm FcyR, FceR. Cc FcyR bao gm FcyRI, RII, RIII l n h n g
t h th b m t lin k t vi phn Fc ca cc phn t IgG. Cc th
t.h Fcy c bc l trn b mt t bo thc bo lym pho B, t bo
KK v cc t bo n an g c tua. C hng ng vai tr quan trn g

t rong p ng min dch th dch.

FACS: M y p h n h n g t bo bn g tia h u n h q u a n g h ot ha
(F lu o rescen ce-a ctiv a ted cell sorter). M y d n g o kch thc
l bo, tn h ch t c h t v ph t qu ang khi cc t bo ny lin
k t vi k h n g th nh du hunh qu ang kh i ngi ta cho 1 t
bo i qua m t m y p h t h in quang hc c chm tia ch iu qua.
V ic p h n tch m t t bo th eo cch ny c gi l o dng ch y
t bo (flow cytom etry) v m y ny c gi l flow cy to m eters
lioc gi l cell sorters.
P o ll i c u le r c e n t e r c e ll ly m p h o m a ; B nh u lym pho dng B
Iiang lym ph o hoc cc m lym pho.
F r a m e w o r k r e g io n s : Cc v n g gi k h n g b in i nm
xen gi a cc k h u vc bin i ca p h n t Ig v cc th th t
bo T. V n g ny gi p cho phn t protein tng n n h cc
khu vc siu b in c th tip xc vi k h n g ngu yn .
G protein: L m t dng protein nm bn trong m n g t bo
lin k t vi G TP v lm bin di G TP th n h G D P trong qu
trn h tru yn tn h i u t bo. C 2 k iu protein G, k iu 1 heterotn m e (vi 3 tiu n v l a,p , y), kiu 2 l p rotein G nh hn v
d nh protein G R as v Raf, n tc d ng xui ch iu vi n h iu s
k in tn iy n tn h iu xuyn qua m ng.
G A LT; Cc m lym ph o lin k t vi rut.
G E F ; G u an in e nu cleotid e exch an ge actor: Y u t trao i nuc le o tit G uan in .
G e n e c o n v e r s io n : S bin i gen, xy ra chim v th to
ra tn h a d n g ca cc ih th nhn b it im m u n oglob u lin . S
bin i gen th ng xy ra vn g V.

296
G e n e k n o c k o u t ; L m t b it ng ch r s ph b m t gen

bng phng php ti t hp ging nhau.

G e n e t h e r a p y ; Liu php gen, phng php cha b n h b n g

cch lm bin i gen ho<c a mt gen mi vo thay th cho gon

gy bnh.
G c n e t ic im m u n iz a t io n ; Gy m in dch di tru yn , l m t k
th u t vi to ra s p ng m in dch th ch ng.

Germinal centers: Cc trung tm mm, l nhng v tr

c c t bo B t n g sin h (phn chia m nh m ), c chn lc dng,
dc chn trng th n h v xy ra ap op tosis (ch t th eo ch ng
trnh).
G e r m lin e d iv e r s it y : T nh da dn g dn g m m , th n g ni v
s cla d n g ca cc th ih n h n b it k h n g n gu yn l nh s
tha k ca n h iu m nh gen m ha cho cc khu vc V. K iu a
dn g ny khc vi kiu da dng do s sp xp li ca gen hoc do
s biu hin t bin som a ca gen.

Goodpastures syndrome: L mt bnh t min trong cc

t k h n g th (au toan tib od ies) p h t sin h ch n g li lp m n g c
bn hoc cc collagen kiu IV y ra b nh ph h y m ch m u.
B ny n h an h chii chuyn sa n g c tnh.
G r a ft r e j e c t io n ; S thi b m nh ghp.
G r a n u lo c 3'te; Cc bch cu n h n a h n h cha n h iu h t.

Granulocyte - macrophage colony - stimulating factor

(GM - CSF) : L mt cytokine tham gia vo qu trnh sinh
trng v b it ha ca cc t bo dng bch cu v dn g m ono
cng tham gia Vo bit ha v sinh trng cc t bo c tua
(d en d rilic cells), di thc bo v bch cu dng ht.

Graves disease: L mt bnh t min trong xut hin cc

khng th chng li th th nhn hocmon kch thch thyroid, t
d gy ra s sn xuL (u mc hocmon thyroid v gy bnh
cng nng tuyn gip (hyperthyroidism).

H antigen, histocompatibility antigen; Khng nguyn ph

hp t chc (k h n g n gu yn ph hp m). V d M H C (M ajor his-

tocompatibility complex) l khng nguyn ph hp m ch yu

c vai tr quan trng n h t trong p ng m in dch. M H C ca
chut dc gi l H - 2 .
H a p lo t y p e ; K iu n bi.
H a p te n s ; L nh ng phn t nh c tn h k h n g n g u y n n h n g

kling gy ra p ng min dch. Hapten cn c lin kt vi

297
mt p ro tein m an g (protein carrier) s to th n h m t k h n g
n gu yn (Im m u n ogen ) gy ra p n g m in dch sin h k h n g th
hoc p n g m in dch dng t bo T.

Hashimotos thyroiditis: L mt bnh t min pht trin

dai d n g cc k h n g th chng li cc k h n g n gu yn c h iu thyroid. C h n h n h n g k h n g th ny s huy ng t bo N K xm
nhp v o cc m v lm tn thng m hoc gy vim .
H a lp e r C D 4 T c e lls ; L nhng t bo T CD4 b tr (TH) gip
cho cac t bo B s n x u t kh n g th trong p n g m in dch th
dch. Cc lym p h o TH bao gm T H l v T H 2 trong TH 2 sn
xu t c y to k in e IL-4 v IL-5.
H e m a g g lu t in in : C ht gy ng ng kt, v d cc lectin .
H e m a t o p o le s is : L qu trnh to ra cc yu t t bo ca
m u bao gm hng cu, bch cu v tiu cu. T t c n h n g t
bo m u u c bt ngun t cc t bo ngun to m u a
nn g (p lu rip o ten t hem atop oietic stem cells).
H e m o l y t ic d i s e a s e o f t h e n ev v b o rn : L m t b nh tan m u
(ta tr s sin h . B n h ny xy ra do bt ng k h n g n gu yn
nhm m u Rh gia c th m v tr s sinh.

Hereditary angioneurotic edema; Bnh ph mch thn

kinh di truyn, do thiu ht gen ca cht c ch Cl (Cl inh)
Irong h thng hot ha b th.
H e t e r o z y g o u s : D hp t biu h in n h n g c th m an g 2
alen k h c n h a u ca cng 1 gen.
Heymanns nephritis: L bnh vim th n c to ra cho
dng v t k h i tim vo chn g cc t bo biu m Vig.

Hgh endotheian vemeles: Mao mch ni m. L nhng

m ao m ch c bit c tm th y cc m lym pho. Cc t bo
lym p h o di c h u y n t m ch m ng i vo cc m lym p h o b n g cch

lin kt v di ng i qua cc t bo ni m theo nhng ng

m ao m ch n y.
H ig h - z o n e t o le r a n c e : S d u ng np liu k h n g n gu yn cao.

(S dung np khi tim khng nguyn c th cc liu thp v

cao).

Hinge region: Vng khp ni ca phn t khng th, c th

dc gi l vng bn l, gip cho phn t khng th mm do
linh n g cho php cc "cnh tay" Fab d an g ra gc rng hp
khc n h a u lin k t vi cc epitop k h n g n gu yn .

298
H is t a m in : L m t dn g am in dn x u t c a h istid in c ti t

ra cc ht ca t vo Mast. Khi khng nguyn (thng l allergen) lin k t vi IgE trn t bo M ast s lm gii ph ng h ista m in
cc t bo ny, gy ra hin tng co m ch v co c trn, to ra
hin tng qu m n phn v (qu m n typ I).
H IV: V iru s gy bnh su y gim m in dch (H u m a n Im m u nod e-

ficiency Virus), bnh do virus gy ra l hi chng suy gim min

dch mc phi (AIDS).
H LA: (H u m an L eulcocyte A ntigen): K h n g n g u y n t bo bch
cu ca ngi; cn c n gh a l M HC (M ajor H isto co m p a tib ility
C om plex) ca ngi. Cc ch ci t sa u H LA, v d H LA-A l
ch r cc locus rin g cho c th , cn cc s' l chi r a len , v d
H L A -A 0 2 0 1 .
H L A -D M : L m t phn t tham gia vo qu trn h loi b

chui bo mu li v t mnh peptit khng nguyn vo rnh ca

p h n t M HC lp II trong c c h trn h d i n k h n g n g u y n ca
M HC II cho lym ph o T-CD 4.
ch u t n h t protein tng ng l H - 2 M.

Hodgkin's disease: Bnh Hodgkim, l bnh ung th ca h

m in dch c c im l dng t bo B b t b in to ra cc t

bo to ln, gi l t vo Reed - Steinberg. C t nht hai dng t

bo rt k h c nh au, l u lym pho H odgkim v h ch u s
(nod ular sclerosis).

Homeostasis: Trng thi sinh l bnh thng, trng thi

ny, cc t bo lym ph o ngi k h n g b n h im k h u n lu n lun

c s lng bnh thng v n nh.

H o m o o g o u s r e c o m b in a t io n : S t i t hp t n g n g cc
gen ca t bo c th b ri lon hoc b ph hy b n g k th u t
t i t hp tng ng vi cc bn sao c a v o tro n g c
cc trn h t c lm sa i lch. K hi a cc gen c trn h t sai
lch vo t bo, ch n g s t i t hp chn lc vi cc g e n c a t
bo qua cc v n g cn li ca trn h t t ng ng, th a y t h gen
chc n n g b n g m t bn sao k h n g c chc nn g.
Host - versus - graft disease (HVGD): B n h ca phn ng
th i b m n h ghp d gen k h i m n h gh p ch n g l i v t ch.
T h u t ng c d n g ch yu trong cy ghp ty x n g b th t
bi.

Humanization: To ra c tnh ca ngi thut ng ch ra

kh n n g ca cng n gh gen s d n g gen c a ch u t n h t m ha

299
"ho v n g siu hiii ca khng th ddn dng c chn trong th
/i n b iu h in trn phage c ci vo cc v n g k h u n g ca cc
?en Ig ca ngi. K hng ih Li t h|) iy c tn h c h iu m ong
m un n h n g kling gy ra d] ng m in dch kh i a vo cd th
"a ngi c cha bnh.
H u m o r a l I m m u n ity : M in dch th dch, c to ra c hiu
qua tru n g gian k h n g th. Tnh m in dch th dch c th c
'khuyn cho cc c th nhn khng gy m in dch bn g cch dng
n u yt th a n h m in dch c kh ng th dc hiu.
H y b r id o m a s : Th lai. c to ra d s n x u t k h n g th n
'lng (M onoclonal anti body). C hng l dng t bo lai nh s
'iung hp gi a cc l bo B sn x u l k h n g th c h iu vi cc
l bo n tu nyelom "sng bt t". N h vy th loi c hai u
'im l cc kh n n g sin h sn cao v lin tc sn x u t ra k h n g
ih dn dng dc hiu theo m un.
H y p e r a c u t e g r a ft r e a c tio n : S th i b m nh ghp cp tc
do k h n g th t nh in hnh th n h t c th n h n ch n g li
khuig n g u y n ca m nh ghp.
H y p e r e o s in o p h ilia : T rng thi bt bnh thng v s lng
'u cao ca cc bch cu a axit trong m u.
H y p e r im m u n iz a t io n : G y m in dch lp li t trn g thi
m in dch m c cao hdn.
H y p e r s e n s i t iv i t y ; S qu m n cm , qu m n. Cc phn ng
<ju m n c phn loi th n li 4 kiu: Q u m n typ I c s tham
a ca IgE lm khi dng cc t b<o M ast tit h ista m in gy
phn ng co m ch v co c trn, qu m n typ II c s tham gia
ca IgG ch n g li cc k h n g ngu yn ca b m t t bo hoc
k h n g n g u y n tru n g pian, qu m n ty) 111 c s th am gia ca
phc h k h n n gu yn -k h n g th v qu m n typ IV l qu m n
c s th am gia ca cc lym pho T.
H u p e r v a r i a b l e r e g io n s : Cc vn g siu bin, nm p h n b
th n h ba v n g nh t khu vc bin i (variab le dom ain) ca
phn t k h n g th to ra s tip xc vi k h n g n gu yn .
iC 3b : M n h b th bt hot dc to ra t s p h n hy c 3 b.

ICAMS (Inter cellular adhesion molecule); Cc phn t

kt dnh lin k t gia cc t bo, l n h ng cu t gn (ligan d s)
li vi cc c h t in tegrin ca t bo bch cu, c vai tr rt quan
Irng trong s lin kt gia cc t bo lym pho v cc t bo bch
cu k h c vi m t s L bo trong c cc t bo trn h din

300
k h n g n gu yn (APC) v cc t bo ni m cc ICAM l th n h
v in ca m t h ln cc Ig.
IC A M l: L m t cu t gn quan trn g n h t i vi cc integrin C D ll a , C D 18 hoc L FA - 1 . N n h a n h c h n g to cm np
trn cc t bo ni m b nh im v c va i tr quan trn g tronp
p ng vim .
IC A M 2: Lin tc bc l mc thp ni m.
IC A M 3: Ch bc l cc t vo bch cu v c vai tr qiiaii
trng tron g s k t dnh gia cc t bo T v cc APC, C7 C bit VI
t bo c tua.
I m m u n o g lo b u lin ; Cc globulin m in d
I c c o s o m e s : L cc m nh nh ca m n g c bao bc b n g cc
phc h m in dch, trong phn b cc qu trn h tin trin ca
cc t bo n an g c tua ca cc nan g lym pho.
IC O S: L m t protein c quan h vi C D 28. C m t cc t
bo T h ot ha c th gip tn g cng p n g m in dch qua
tru n g gian t bo T. Protein .ny lin k t vi m t cu t gn khc
l LICOS p h n v it vi cc phn t B7.
I d io to p e s ; c coi l m t epitop ca m t d n g k h n g th
rin g bit. M i phn t Ig u c kh n n g lin k t vi h n g hot
k h n g th hng ti nh ng c im duy n h t v c gi l cc
id iotyp e (m t typ k h n g th rn g b it, idio: c tn h c bit). M l
idiotyp c to ra t h n g lot cc idiotope.
I d i o t y p i c n e t w o r k : M ng li idiotyp, l tp hp cc th th
n h n b i t k h n g n gu yn ca cc t bo lym p h o hoc c a k h n g
th c h n h th n h do s tng tc n h n b it m in dch ln
nhau gi a chng.
I g a , Igp: T h th ca t bo B hoc C D 79a, C D 7 9 b.
IL: In terleu k in s.
I m m a t u r e B C e lls: Cc t bo B ch a c h n l n h n g t bo
ch mi sp xp l i cc gen chui nn g, ch u i n h v v n g V v
mi ch bc l IgM b m t (m lgM cha bc l y m lgD ).

Immediate hypersensitivity reactions: Cc phn ng qu

m n tc th , l n h n g phn n g qu m n xy ra tn h th eo p h t
p n g li k h n g n gu yn l.
I m m u n e c le a r a n c e : S "khai quang" m in dch l h i n tng
loi b n h a n h ch n g k h n g n g u y n l xm n h p nh k h n n g
tn g hp n h a n h k h n g th h n h th n h phc h k h n g n g u y n

- khng th.

;oi
I m m u n e c o m p le x : Pho h m iii dch.
I m m u n e d e v i a t io n : S phn k m in dch, xy ra s p ng
m in dch i vi m t kh ng nguyn c u th do cc l bo T i|l
hoc T |2 (la m n h i m .

I m m u n e n io d u la t io n : S diu hin m iii dch, bao gm

nhng bin di k h c nhnu truiig p ng m in dch, Im n iu n e responso goiius (Ir gcn os). Cc
(l|) ng m in dch, biu h in
ln h a hnh v di tru yn tron> kim sot cng p n g m in
(ich di vi m t kli;ui< Iituyn rin< bit. Thc t, t t c cc
|)honot.ii|) (biu hin kiu hnh) ca gen Ir l do s lin k t khc
l)it ('a cc m nh )0 |)tit khng ngu yn i vi cc phn t M HC
(lc l)t l M IIC -II. S thiu ht ca cc gen Ir (Ir g en e defect)
thng xy ra n h n g khng phai lun lun nh vy. l do m t
kh n n g lin kt. vi mt popliL k h n g ngu yn n mc kh n g
th y x u t hin p n g m in d c h l a cc t bo T.

Immune snrveillance: S gim st min dch, y l mt

qu trn h c coi l tn ti li-on c th p h t h in v loi tr
(c khi u n g th c thc hin qua tru n g gian cc t bo lym ph<' dc hiu.
I n im u n e s y s t e m : H m in dch, c m t v cc m. cc t
l)o v cc p h n t ih am gia p ng m in dch v i khi c
coi l tn g th ca c ch bo v v t ch.
I m m n ity : T nh m in dch, l kh n n g k h n g li s n h im
bnh.
I m m u n iz a t io n : G y m in dch, m t phng php ch n g
to ra p n g m in dch thch ng b n g cch a m t k h n g
ngu yn l vo c th . phng php ny th h in 2 kiu: gy m in
dch ch dng (active) gy m in dch th ng (p a ssiv e im m unization) nh a m t lng khri th hoc h u y t th a n h m in
dch vo c th n on di v m in dch.
I m m u n o b lo t t in g ; C huyn thm m in dch. y l k th u t
bao gm cc ))rotein dc tch bn g din di trn gel poly acrylam ide (PAG E), sa u dc chuyn th m ln m t m n g nitrocellu lose v c p h t h i n bng s lin kt ca ch n g vi cc k h n g
th c h iu c n h du (v d k h n g th n h d u p h n g x,
ch t h u n h q u an g hoc k h n g th cng hp to p h n n g en zym
ph t m u c trng).
I m m u n o d e f i c i e n c y d is e a s e s : Cc bnh th iu h t m in dch.
Cc b n h n y c th do di tx-uyn (in h erited ) hoc c th tip thu

302
c (acquired) trong i sn g c th. Cc bnh biu h in rnni
kh n n g t bo v m in dch.
I m m u n o d if f u s io n : S khuych tii m in dch, l h in iii^
k h uych tn ca k h n g th v k h n g ngu\'n khi p n h au s
to ra cu n g k t ta, nu k h n g th v k h n g n gu yn c tn h t'
hiu tng tc vi nhau. H in tng ny c n g d n g nhn
dn g k h n p th hoc kh ng n gu yn trong k th u t O u ch torlon g
I m m u n o e le c t r o p h o r e s is : in di m in dch, l m t k th u i
trong , cc k h n g ngu yn c phn t n h n g in di. sau (
dc p h t h in b n g k h n g th c h iu nh kh n n g kh uych
tn ca chn g.
I m m u n o A u o r e s c e n c e : M in dch h u n h q u an g l m t k
th u t p h t h in phn t k h n g ngu yn nh s d n g cc khnt
th n h d.u b n g ch t m u h u nh quang.
I m m u n o g e n e t ic s : Di tru yn m in dch, l m t k h a cnh
n gh in cu phn tch di tru yn cc k h n g th k h n g li cc plirm
t a hn h v di tru yn nh cc k h n g n gu yn nhm m nu, hoc
cc phn t protein ca M HC. M n hc ny c n g d n h cho vic
phn tch di tru yn hoc s d ng k th u t di tru yn ht k no
p h n tch cc phn t quan trng trong m in (lch hc.
I m m u n o g lo b u lin d o m a in s : Cc khu vc Ig l c tnh
c h u n g cho cc protein thuc h ln cc Ig m in dch bao gm cc
k h n g th , cc th th t bo T, cc phn t M HC v n h iu phn
t t ng t c a h m in dch cc khu vc m in dch bao gm h
l gp p c duy tr bn g m t cu d isu lt, cn c gi l np
gp Ig (Im m u noglobu lin fold). C hai k iu dom ain Ig ch yu l
cc dom ain c ( v n g kh ng b in i) vi m t l gYp 3 n h n h v
m t l gp 4 n h n h v cc dom ain V (vn g bin i), mi dom ain
cha thm m t Iihiih ngoi.
I m m u n o h is t o c h e m is t r y : H o m m iii dch, m t k thut
m in dch nh m p h t liin cc k h n g n gu yn m t bo bng
cch s d n g k h n g th cng hp en zym c h iu k h n g n g u y n
p h t h i n di k n h h in vi q u an g hc, kn h h i n vi h u n h
q u an g hoc k n h h in vi in t.

Immunoligical Ignorance: S yn lng min dch, mt hin

tng t d u n g np trong , cc t bo lym pho p h n n g v
k h n g n g u y n ch ca ch n g u c p h t h in tron g m t c
th n h n g k h n g th y s tn cng ca bnh t m in .
T t c cc b n h t m in xy ra khi s y n l n g m in dch b
ph v.

303
I m m u n o l o g i c a l m e m o r y : S ghi nh m in dch. l c
im quan trng ca tnh bo v m in dch, khi da m t k h n g
n u yn vo c th, s ) ng m in dch tip thu v thch ng s
c th h in v c ghi nh li trong cc t bo v ph n t ca
h m in dch. S ghi nh m in dch c tiih c h iu cao v c i
s n g lu di.
I m m u n o l o g i c a l ly p r iv ile g e d s it e s ; Cc v tr c quyn
m in dch. M t s m t bo m t s v tr trong t bo nh no,
k h n g gy h in tng thai b minh ghp. l cc v tr c
q u yn m in dch v do hiu qu ca h n g l o v t l i vi s di
n g t bo v k h n g ngu yn v do c s n cc c h t ha gii ha
ta n nh xitok in c kh n.ng km hm m in dch.
I m m u n o p h ilin s : L nhng p rolein c hot tn h en zym peptidyl - prolyl cis - tran s isom eraso to lin k t gia cc thuc km
h m m in dch cyclosporin A, FK 506 v rapam icin.
I m m u n o p r e c i p i t a t i o n a n a ly s is : P hn tch k t ta m in
'dch l phng php s dng k h n g th c h iu p h t h in cc
p ro tein k h n g n gu yn ho tan hoc irotein m n g ta n tron g ch t
t y ra (d etergen t) c nh du, sa u s d n g tip k

thut in di SDS - PAGKI pht hin bng phng x t ghi

(autoradiography).

Immunoreceptor tyrosine - based activation motis

'(IT A M S): Cc hn h thc hot ha th th m in dch da vo tyrozin. Cc th th ca t bo T v t bo B lun lin k t vi cc
loi p h n t xu yn qua m ng c hot tn h T y ro sin ek in a se. Mi
m t hn h thc ITAM bao gm m t cp YXXL to ra m t k h on g
trn g nh k h on g 1 0 axit am in. C h n g l cc v tr phot
iphoryl ha tyrozin v lm k t hp ty so sin e k in a se vi cc p h n
lin k t ph ot photirozin khc, tham gia vo qu trn h tru yn tn
h iu c a th th.

Immunorcgulation: S iu ha min dch.

I m m u n o s u p p r e s s i v e d r u g s : Cc thuc km hm m in dch.
'ic d n g hn ch s th i b m nh ghp v cha bnh t,
m in c tnh .
I m m u n o t o x in ; c t m in dch.
M t d n g k h n g th c kt hp v ha hc (cng hp) vi cc
,phn t c h t c c ngun gc thc v t hoc vi sin h v t c kh
n n g n h n b i t v lin k t vi k h n g n gu yn c h i u ca t bo
u n g th d i t khi u, cng c th di d n g thu c km hi
m in dch.

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I n d i r e c t C o o m b s te s t: X t ngh im Coomb g i n tip, m t
k iu x t n gh im trong mt dng h u y t th a n h cha bit r
k h n g th c x t nghim bn g cch trn vi cc t bo hng
cu bnh thng. S au ra t bo h n g cu v li trn tip theo
vi m t k h n g th k h n g Ig. N u k h n g th tron g huyt th an h
cha b it r lin k t c vi hng cu th s n g n g k t dc k h n g
th k h n g Ig s c xy ra. T rong khi x t n gh im Coomb
trc tip s d n g k h n g th k h n g Ig gy n g n g k t cc t bo
hng cu p h t h in c hay khng m t d n g k h n g th bao ly
hng cu in vivo trong bnh t m in hoc tron g p ng m in
dch do b t ng k h n g ngu yn nhm m u gi a c th m v th ai
nhi.
I n f e c t i o u s m o n o n u c le o s is : M t b n h gy s"t do nhim
tr n g v iru t E p steim Barr c km theo ni hch lym p h o v m t
mi.
I n A a m m m a tio n : V in sng ty, th u t ng ch h i n tcng tch
ly ch t dch, protein h u y t tng, cc t bo b ch cu b khi
ph t b n g s tn thng c th, b n h im hoc p ng m in
dch t i ch. H in tng ny c gi l p n g v im (in flam m atory resp on se), khi cc t bo c chc n n g m in dch xm
nhp vo m b vim c gi l s th m n h im vim (inflam m tory in iltra te).
I n f lu e n z a ; B n h thng hn.
I n n a t e im m u n ity : T nh m in dch bm sin h , l tnh m in
dch c s n ngay sa u khi m t c th ra i, c m t m i thi im
v k h n g c k h n n g p ng p h n b it c h iu .
I n o s i t o l t r i p h o s p h a t e (IP 3 ): L s n ph m p h n hy ca
in ositol ph osp h olip id di tc d ng ca p h o sp h o lip a se C7. 1P3
lm g i i p h n g ion can xi t ni d tr bn trong t bo li ni
ch t (en d op lasm ic reticu lu m ).
I n t e g r in : L n h n g protein h eterod im e trn b m t t bo
tham gia vo s tng tc t bo, t bo v t bo - c h t n ln gian
bo. C h n g c va i tr quan trng tron g tng tc k t dnh gi a
cc t bo lym p h o v cc t bo trn h d in k h n g n g u y n (APC),
cng n h vai tr di ng cc t bo lym ph o v t bo bch cu
vo m. |3, - in te g rin cn gi l k h n g n g u y n rt ch m (very la te
a n tig en - VLA) l m t h cc in teg rin c cc chui Pi, v Q to ra
k t dn h gi a cc t bo kh c v vi cc protein gian bo.

Interdigitating reticular Cells: Tng t dendritic Cells.

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I n t e r e r o n s ; L nh ng xitokin (cytok inees) to cho cc t bo
km hm s nhn ln ra viru s.
I n t e r f e r o n a: (IF N -a) v in tereron (IKN-P) tng n g c
bch cu v n gu yn bo si (ibroblast) c n g nh cc loi t bo
khc, s n x u t ra tron khi intererom 7 (IFN-y) l s n phm ca
cc t bo TCD4" (h l), T C D 8 " v cc t bo NK. IFN-y c tc
n g h o t ha khi ph t i vi di thc bo (m acrophage).

Interleukin (IL): L thul ng chung cho cc xitokin c

bch c s n xut ra trong d in te rleu k in - 2 (IL- 2 ) l m t xitokin
q u an trn g n h t i vi s pht trin ca p ng m in dch
thch ng.
I n t r a c e l l u l a r c y t o k i n e e s t a in in g : N hum xitok in ni bo l
k th u t cia thm vo trong t bo mt k h n g th k h n g xitok in
c nli du hunh quang.
I n t r a c u t a n e o u s in je c tio n ; Tim vo da, su b c u ta n eu s injection l tim vo di da, in tram u scu lar in jection l tim vo
m ch m u.
I n v a r i a n t c h a in (li): L mt chui p ep tit k h n g bin i
th am gia vo vic hng dn v bo v s lin k t ca phn t
M HC lp II vi m nh p eptit k h n g n gu yn s c trn h din.
C hui p e p tit li c coi l phn t bo m u (chaperon) cho qu
trn h lin kt M H (M I p ep lit khng ngu yn .

ISCOMS: L cc phc h kch thch min dch ca khng

riXuyn c gi trong ch t nn lipit. C ht nn lip it ny ng vai
tr n h m t t ch t v cho php k h n g n gu yn i vo t bo
c li t. S au khi dung hp lip it vi m ng sin h ch t t bo.
I s o e l e c t r i c f o c u s in g : in di hi t an g in, in di phn
v n g d a n g in , l k th u t din di trong d cc phn t protein
di ch u y n tron g mt grad ien t |)H c to ra bn g m t d u n g dich
cc a m p h o lit. Khi mi m t protein t dn m t v tr n h t n h
mt pH no d tr n g vi pH im dn g in ca p rotein th n s
k h n g tch in, khng di chuyn, s hi t ti im n g in
ca ch n g.
I s o t y p e s : Cc bin dn g phn t Im m u n oglob u lin thuc v
cc lp k h c nhau bao gm: IgM, IgG, IgA. IgA, IgE, mi ch n g
c m t chui nn g phn bit nhau do cc gen v n g c quy nh.
M t Isotyp e ca k h n g th xc nh cd c h h iu qu lin k t vi
k h n g n g u y n . Cc chui n n g c cc khu vc c k h c n h au c
m ha t cc exon 3 ni vi cc v tr V (D) J c sp xp li.
T cho p h p mt phn t k h n g th c m t khu vc V b in i

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ca chui n n g lin kt vi cc Isotyp e cha v n g c k h c nh au
to ra s ti t hp som a.
I s o t y p e s v v itc h in g : Khi ng tn g hp cc d n g Isotyp e. M t

khng th u tin c sn xut trong p ng min dch th

dch l IgM. Tuy nhin t bo B c hot ha tip theo s
khi ng tn g hp cc k h n g th Isotyp e khc n h a u n h IgG,
IgA, IgE v.v. V ic khi ng tng hp cc Isotype k h n g t c n:

vo tnh c hiu ca khng the nhng lm bin i chc ni

gy hiu qu ca khng th v kh nng ny l do s ti t hp
trong qu trn h sp xp li cc v n g gen V v cc exon v n g (

ca chui nng.
I s o t y p i c e x c lu s io n : S loi tr Isotype. M t vic s dri',
ch m t chui nh

K
hoc

t r o n g p h n t k h n g t h d o t b o H

tng hp ra.
J g e n e s e g m e n t ; M nh gen ni vc tm th y m t s
k h on g cch 5 ca cc gen c trong Ig v trong locu s c a th th

t bo T. Chng hn cc chui TCRp v TCR cn c mt mnh

gen D (d iversity gene: gen to tn h a dng) c s p xp cu n g
vi m n h gen J h n h th n h m t exon y v n g V.
J a n u s k i n a s e s (JA K s): L m t ty ro sin e k in a se c h o t ha
b n g s k t hp vi cc th th xitok in . Cc k in a se n y phot-

phorin ha cc protein nh bit l: cht truyn dn tn hiu

v cc cht hot ha phin m (Signal Transducers and Activators o f T ran scrip tion - STATs). Cc STAT ly bn h th n g c
tm th y trong cytosol nh ng s di ng vo n h n t bo khi c;
photphorin ha v s hot ha h n g lot gen.
J u n c t i o n a l d iv e r s it y : S a d n g cc m nh g en ni (xcin

mc gen J)
Killer activatory receptors (KARs): L th th b mt t
bo ca cc t bo NK hoc cc t bo T gy c. C h n g l n h n g

th th hot ha cc qu trnh dit t bo.

K ille r T c e ll' D an h t ch u n g ch cc t bo gy c
K in in s y s t e m : M t dy phn ng en zim ca cc p rotein b
tng c t( ra do s tn thiiR t bo. gy nn m t s hii)
tng vim , c n g bao gm c qu trn h h ot m ch p e p tit bra-

dykinin.
C-Kit: N i v th th C-Kit c m t tron g qu trn h p h t trin
cc t bo B v n h n g t bo bch cu khc lin q u an n m t

yu t t bo ngun nm cc t bo ly xng. Kit c hot ng

protein kyrosine kinaso.

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K it: B sin h phm thng c d n g trong xt n gh im ha
sin h v m in dch.
K u p f f e r c e lls ; L cc thc bo nm gan chc n n g thu
dn rc th i v t bo cht t mu n h in g cha r c hot ng
khi dn g p n g m in dch.
L a n g e r h a n s c e lls ; L nhng thc bo c tua (phagocytic
d en d ritic cells) c tm thy lp biu b. C hng c th di ng
t biu b dn cc hch bch huyt kh u vc, chng dc bit
ha th n h cc t bo c tua.
L a r g e p r e -B c e lls ; Cc t bo tin n kch thc ln thng c
tli tli tin B v sau ny s m t di khi ch u yn d n g th n h cc t
bo tin B nh.
L A T ; X e m L i n k e r o 'a c t iv a lio n in T c e lls .

L a t e n c y : S y n lng. Mt s viru s khi xm nhp vo l bo

kh ng n h n ln hoc ti ban v trn g tlii yn lng. Khi viru s
c ti h oi ha v nhn bn chnf s gy ra bnh tt.
L a t e - p h a s e r e a c tio n : Phn n )ha chm : l n h ng ])hn
ng qu m n qua trung gian lyp 1 din ra dai dng v thng di
k h n g vi th u c a n tih ista m in e.
L e n t i v ir u s e s : L mt nhm cc retrovirus (viru s cha gon om e AR N ) bao gm HIV gy bnh A ID S ngi. C hng c thi
gian bnh lu di.
L e p r o s y : B n h i)hong (hui) do vi khun M yco bacteriu m leprae
gy ra n h iu d n g bnh phoiif. C 2 d n g phong khc nhau l:

le p ro m a to u s le p ro sy I)1U hiii kli nng nhn lii ri cao ca

vi k h u n gy bnh v sn xut rt n h iu k h n g tli m khnt
gy dp ng m in dch qua trung gian L bo. D n g th 2 l
t u b e r c u l o i d le p r o s y Irng d bnli nluu hu nh kh ng c
k h n g th hoc rt l kh ng th nh ng m tn thng v c
b iu h in m n h tn h m in dch qua Irung gian t bo.
L e u k e m ia ; U n g th bch cu, m i d n g ung th c tnh biu
h in s lng rt: cao I( l bo c lin h trong m u. li n h I th
biu hin cc t bo lym])ho. cc l ho ty myolocyLic hoc
m onocytic.

Leukocyte: Thut ng ch cc t bo l)ch cu ni rhung bao

gin ly m p liocyte, polyinorphonuclear Icuk ocytes v m onocytcs.
L e u k o c y t e c o m m o n a n t ig e n ; Cm b it ha C D 45 ch u n g cho
bach cu

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L e u k o c y t e u n c t i o n a l a n t i g e n s hoc L F A s: L n h n g p h n
t k t d n h . Ch.ng h n L F A 1 l m t P 2 in teg rin ; L F A 2 l m t
th n h vin c a h ln Im m u noglobu lin ; L F A 3 l C D 58. L F A 1 c
vai tr q u an trn g lm k t dnh t bo T vi cc t bo ni m v
cc t bo trn h d in k h n g n gu yn .
L e u k o c y t o s i s : B n h b iu h in t n g s lng t bo bch c u
tron g m u. B n h ny ni ch u n g xv ra tron g tr ng hp n h i m
tr n g c tn h .
L e u k t r ie n : L n h n g c h t ha g i i c b n c h t lip it g y
v im . Cc c h t ny b t ngu n t a x it arach id on ic, C h n g c
cc i th c bo v n h n g t bo k h c s n x u t ra.

LICOS: L mt cu t gn (ligand) ca ICOS, mt protein c

li n q u an n C D 28 do cc t bo T h o t ha c k h n n g g y
t n g h p c h n g

n h n g t b o c t u a h o t h a h o c c c t b o

B.
L i g h t z o n e : X em g erm in a l con ters.
L i n e a r e p i t o p e : X em co n tin u o u s ep itop e.

Linkage disequilirium; S khng cn bng trong lin kt,

ni v cc alen nhng locus ca phc h MHC c di truyn
lin k t vi n h a u n h i u hn so vi d bo th eo t n s" li n k t c a
m i c th .
L i n k e d r e c o g n i t i o n : S n h n b i t li n k t, cc ep ito p c t
bo B v t bo T b tr c n g c n h n b i t li n k t vi n h a u
h o t ha t bo B.

Linker of activation in T cells (LAT); L mt dng protein

th ch n g n m tron g t bo c h t c ch a m t s gc ty ro sin e. C(C
gc n y c th c p h otp h orin ha b n g ty ro sin e k in a se ZAF-70'.
P rotein n y li n k t vi tp hp lip id m n g v iu ha h t h p
cc s k i n tr u y n tn h iu tron g s h o t h a t b o T.
L o w - z o n e t o l e r a n c e : S d u n g n p v n g th p (xem H igh-zon(e
to leran ce).

LPS-binding protein (LPB): Protein lin kt vi LPS

(L ip o p o ly sa cch a rid e-n i c t th n h t bo vi k h u n ), L P S tr(C
k h i t ng tc vi C D 14 c a i thc bo, n c n li n k t vi L P B .
L - s e le c t in ; L m t p h n t k t d n h th u c h s e le c tin (C
tm th y tron g cc t bo L ym pho. L -se lec tin li n k t vi C D 3 4
v G lyC A M - 1 n m trn cc m ao m ch x en k cc t bo ni m('
g i p khi n g s di c h u y n c a cc t bo L ym p h o s k h a i (na -

309
iv e ly m p h ocytes) i vo m lym pho. L -selectin c n g c gi l
C D 62L .
L y m e d i s e a s e : B n h n h im tr n g m n tn h xon k h u n Bor-

reliaburgdorferi,

x o n k h u n n y c th t r n t h o t s p n g

m in dch.
L y m p h : D ch ngoi bo c tch ly tron g cc m v c
v n ch u v n th eo m ch lym ph o tr v h th n g bch h u y t di qua
Vig ngc vo m u.
L y m p h n o d e s : H ch bch h u y t, c quan lym p h o th cp
hoc ngoi vi.
L y m p h a t ic s y s t e m : H thVig lym pho, bao gm Ce k n h
lym p h o v m t bo gm cc h ch lym ph o, m P ey e r v n h n g
th n h p h n h^mpho c t chc trong lch.
L y m p h a t ic v e s s e l s h o c ly m p h a t ic s : Cc m ao m ch lym pho cha dch lym p h o vn ch u y n vo h thVig lym ph o.
L y m p h o b la s t : M t d n g t bo lym p h o kch thc ln c qu
Irnh tng hp A R N v p rotein m n h m.

Lymphocytes: Cc t bo lympho bt ngun t ty xng v

c b it ha th a n h 2 dng lym ph o B v lym ph o T.
L y m p h o c y t e u n c t i o n - a s s o c i a t e d a n t i g e n s : X em L eukocyte u n ctio n a l a n tig e n s.
L y m p h o c y t e r e c e p t o r r e p e r t o ir e : K ho d tr th th ca
t bo lym pho, l tn g th t t c cc th th k h n g n g u y n nm
trn t bo B v T ca c th.
L y m p h o c y t i c c h o r i o m e n i n g i t i s v i r u s (L C M V ): L m t
d n g viru s gy b nh vim m n g no d chuL v i kh i xy ra

ngi. Vi khun ny c dung trong nghin cu thc nghim.

L y m p h o id d e n d r i t i c c e lls : N h n g t bo bch cu c tu a b t
ngun t cc m lym ph o, khi b t ngu n t cc t bo m yeloid th
c gi l t bo tu a dng tu m y e l o i d d e n d r i t i c c e l ls .

Lymphoid organs: Cc c quan lympho.

L y m p h o k in e : L n h n g xitok in c sn x u t t cc t bo
lym pho.

Lymphomas: Cc khi u (ung th) ca cc t bo lympho,

nm tron g cc m lym p h o hoc tron g cc m t bo k h c n h n g
kh ng i vo m u. C rt n h iu k iu lym phornas b iu h i n s
bin d n g cc g ia i on phat trin kh c n h au ca cc d n g t bo
lym p h o B v T.

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L y m p h o p o ie s is : S bit ha cc t bo b t n gu n t m t t
tin ch u n g ca dng lym pho.
L y m p h o t o x in (LT); c t' lym pho, ch n g h n y u t hoi t
u n g th TN F-P (P-tum or n ecrosis factor), m t x ito k in do cc t
bo TC D 4 vim ti t ra nhm gy c trc tip i vi m t s bin
dn g t bo.
L yn ; Xem tyrosin e k in a se.
L y s o s o m e s : Cc bo quan c tnh a x it ch a r t n h i u en zim
th y ph n. Cc k h n g ngu yn l khi b th c bo c bao bc
t r o n g b c m n g e n d o s o m e s d u n g h p v i c c t h ly s o s o m e v b

tiu ha.
L y t ic g r a n u le s : Cc h t phn gii ch a perforin v gran zym e
c c tn h q u an trng ca n h ng t bo T g y c.
M c e lls : N h n g t bo c np gp lin k t vi cc m lym pho
ca rut (gu t-a sso cia ted lym phoid tissu e-G A L T ) tip n h n cc
k h n g n g u y n v tc n h n gy bnh. C h n g c n g c th l con
ng l y n h im HIV.
M a c 1 ; C ht k t d n h in tegrin C D llb : C D 18 h oc C R 2
M a c r o g lo b u lin : N h n g globulin c trn g l ng p h n t ln,
thng l cc protein bo tng bao gm IgM v a 2 m acroglobulin.
M a c r o p h a s e a c t iv a t io n ; S hot ha i thc bo, n g vai
tr quan trn g trong vic kim so t n h im tr n g v c n g gy ra
s tn thng cc m xu n g quanh.

Macrophase mannose receptor: Th th nhn bit mann o se c a i th c bo.

M a c r o p in o c y t o s is : S un g bo m c cao. c thc hin

bi cc t bo c tua (dend ritic cells).
M a d C A M - 1 : M t d n g phn t k t d n h c a cc t bo nim
m c c n g i l m u c o s a l a d h e s in e , c n h n b i t b i c c p r o t e i n
b m t c a t b o ly m p h o

M a jo r b a s i c p r o t e in : M t dn g p rotein b a se ch y u c cc
bch cu a a x it (E osin op h ils) ti t ra n h m khi n g cc t bo
m ast, gy v cc h t trong t bo ny gii ph ng ra h ista m in .

Major histocompatibility complex (MHC); Phc h ph

hp m ch yu , ngi c gi l H LA (H u m a n L eu k ocyte Antigen ).

Original antigenic sin: S vi phm khng nguyn gc, m l

kh n n g p n g m in dch k h n g th c a ng i i vi nhng

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q u y t n h k h n g n g u y n (epitopo) b sai lch gi a ch n g v iru s
n g u y n g c v c c v i r u s c in i ( u a n h t r o n g k h i b q u a e p it o p e

c tn h sin h m in dch cao.

P a n n in g ; gn lc. cc di qun the t bo lym ph o c th c
p h n lp b n g cch gn lc trn cc da petri ph cc k h n g th
n dn g chVig li cc du hiu (du n m arker) b m t ca mi
loi t bo t c th tm ra nhng qun th lym ph o rin g
b it lin k t c hiu.
P a r a c o r t i c a l a r e a hoc P a r a c o r te x : L m t v n g cha t
bo T ca hch bch h u y t nm ngay bn di p h n n a n g ca v
m y ch y u bo gm t bo B, vn g cn v.
P a r a s it e s : T h k sin h

Paroxysmal nocturnal hemoglobinuria (PNH): L bnh

th iu h t cc p rotein iu h.a b th vi phm vo con ng
h ot ha dn n h i n t n g ta n m u tc thi.
P a r t i a l a g o n i s t p e p t id e s ; Xem altered p ep tid e ligands; Cc
pop tit n g v n m t ph n
P a s s i v e h e m a g g l u t i n a t i o n : S ngng k t h n g cu th ng
l k th u t p h t h in kb ng th trong h n g cu c bao
ph k h n g n g u y n v cc kh ng th c p h t h in s gy
ng ng k t cc t bo h n g r^u ph kh ng ngu yn .

Passive immunization. Gy min dch th ng, bng cch

tim k h n g th h oc k h ? n g h u yt than h vo c th tip n h n
cha h b i t p n g m in dch ( lp vi gy m in dch ch
ng c th c h in cc c th bit p ng m in dch).
P a t h o g e n i c m i c r o o r g a n is m hoc p a t h o g e n s ; Cc vi sin h
vt gy bnh.
P a t h o lo g y : M n bnh, l hc l mt klioa hc n g h in cu bnh
P a t t e r n r e c o g n i t i o n r e c e p t o r s (P R R s): Cc th th n h n
d n g m u, th u t ng dng chi cc th th lin k t vi cc
m u phn t c q u an h vi vi sin h vt gy bnh.
P a t t e r n r e c o g n i t i o n m o le c u le s : li cc p h n t th th ca
h m in dch bm sin h d ng d nhn bit b m t k h n g n gu yn
ca vi sin h v t g y b n h .
P E C A M (C D 3 1 ); M t phn t k t dnh t bo c tm th y
cc t bo ly m p h o v khp ni ca cc t bo b iu m. S tng
tc gi a cc C D 31 gi p cho cc t bo bch cu ri khi m ao
m ch m u v i 'vo m.

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P e n t a d e c a c a t e c h o l : L m t ch t ha hc tron g l cy
T hng x u n (D ichroa febrifu ga) c c t, c h t ny gy ra hin

tng qu mn do nhim cht c ca cy thng xun.

P e n t r a x in s : M t d n g lectin c bn c h t protein bao gm 5
tiu n v ging nhau. V d protein phn n g c v m t s' pro-

tein huyt thanh amyloid cng l nhng pentraxin.

P e r f o r in : L m t protein to ra l th n g ca m n g kh i dc

polyme ha, c ngha quan trng trong c cht dit t bo VI

k h u n . P erforin c cc t ba T gy c v N K ti t ra kh i cc

t bo ny tip xc vi cc t bo ch c hiu.
P e r l a r t e r i o l a r ly m p h o id s h e a t h (P A L s): P hn bn trong

ca vng li l lch cha ch yu t bo T.

Peripherial blood mononuclear cells (PBMN); Cc t bo
n n h n ca m u ngoi vi bao gm cc lym p h o v cc m ono i

vo mu ngoi vi.

Peripheral or secondary lymphoid organ: Cc c quan

lympho ngoi vi hoc th cp: hch bch huyt, lch, cc m lym-

pho, nim mc.

Peripheral tolerance; Dung np ngoi vi, mt qu trnh tip
nhn cc t bo lympho trng thnh m ngoi vi tri vi dung
np tru n g ng (Central tolerance) l qu trn h tip n h n cc t

bo lympho cha chn trong qu trnh pht trien ca chng.

P e y e r s p a t c h e s : m Peyer, l tp hp cc t bo lym pho

dc theo rut non

Phage display library: Th vin biu hin trn thc khun
th, mt k thut c s dng pht trin nhng khng the
mi c tnh c hiu bt k da vo qu trnh tch dng (cloning)
cc gen m ha cho v n g V ca Im m u n oglob u lin dc b iu hiii
trn cc p h age.
P h a g o c y t o s i s : S n bo, m t qu trn h n u t cc v t th l

ca cc t bo thc bo. V d i thc bo, bch cu trung tnh.

Cc vt th khi c nut vo nhng t bo ny c th c bc
li b n g cc bc m n g (vesicle) c gi l p h agosom e. T ip theo

cc phagosome ny s dung hp vi mt hoc nhiu lisosome

h n h th n h m t th gi l ph agolisom e. T rong th n y cc tc

nhn gy bnh hoc vt th l s b tiu ha, b ph hy bng cc

enzim ca lisosome.

313

Phosphalidylinositol bisphosphate (PIP2): L mt photpholipid lin kt mng, b phn hy bng phospholipase C-y to
ra cc phana t tn hiu diacylglycerol v Inositol trisphosphate.
Phospholipase C-y; L mt enzim quan trng truyn tn
hiu. N dc hot ha bng protcin tyrosine kinase. V phn
mnh tyrosine kinasc li c hot ha bng s kt hp gia
khng nguyn v th th ca t bo.
P la s m a : L m l cht dch ca m u cn gi l h u y t tng.
P la s m a c e lls ; T bo plasm a l dn g b it ha cui c n g ca t

bo B ch yu c chc nng tit khng th. Cc t bo plasma

c tm thy trong phn ty ca hch lympho, trong phn li
mu ca lch v c ty xng.
Plasmablast: Mt dng t bo B nm trong hch lym pho c
nhiu c im ca t bo plasma.
P l a t e l e t a c t i v a t i n g f a c t o r (P A F ): Y u t h ot ha tiu cu.

l cht ha gii lipid tham gia vo dy chuyn ng mu.

P la t e le t s :

L cc tiu cu c vai tr quan trn g trong ng

mu c hnh thnh t cc t bo c nhn khng l (megakaryocytes), cn c tn l thrombocyte.

P - n u c le o t id e : L trnh t n u cleotid e c tm th y cc v n g

n gia cc mnh gen ca cc gen vng V m ha cho cc th

th. P-nucleotide dc lp li o ngc ti vng cui ca nhng
mnh gen ln cn to ra nhng dng cp tc gip cho qu trnh
ti t hp. C h n g c th hn h th n h nh ng trn h t palind rom ic

nn gi l P-nucleotide.
P o is o n Iv y ; Cy Thng xun c l cha c h t c pen tad ecacatech ol (tn khoa hc: D ichroa fehrifuca Lour).

Polyclonal activation; S hoi ha a dng, l qu trnh

hot ha li ko theo nhiu dng (nhiu clone) t bo khc nhau.
Cht mitogen (cht kch thch phn bo) gy ra hin tng hot
ha nhiu dng t bo c gi l polyclonal mitogens.

Polygenic: Ni v h thng gen m ha cho MHC cha ng

mt s locus gen. Nhng MHC ny u c chc nng ging nhau
v mang tnh a hnh v c nhiu alen trn mi mt locus.
Poly-ig receptor: Th th lin k t vi cc Ig polym e c b it
l IgA. Th th ny nm mng t bo lp biu m.
P o ly m e r a s e c h a i n r e a c t i o n (P C R ): P h n n g tr n g hp

chui dng nhn mt on gen hoc phn t ADN.

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P o ly m o r p h is m : T nh a hnh, s tn ti n h iu d n g khc

nhau ca mt vt. Tnh a hnh di truyn l s bin dng ca

m t locus gen trong cc bin dn g ph t sin h tn s ln hn
1 %. Phc h M HC l m t n gen a h n h n h t ngi.

Polymorphonuclear leulcocytes; Cc bch cu nhn fv

hnh, bch cu nhn nhiu thy v c ht.
P o ly s p e c i c it y : T nh a c hiu, m t sT k h n g th c kh

nng lin kt vi nhiu khng nguyn khc nhau, c tnh a c

hiu hoc tnh a phn ng.
P o s o t i v e s e l e c t io n : S chn lc dng tn h ni v qu trnh

chn dng t bo T tuyn c. Chi cc t bo T c th th nhn

bit cc k h n g n gu yn c trnh din bi ch n h cc M HC ca

bn thn mi c th chn trng thnh Thymus (tuyn c)

Pre-B.Cell receptor hoc Pre-B.Cell receptor complex:
Th th hoc phc h th th ca t bo tin B. l s biii
hin (bc l) ca t nht loi protein lm cho t bo tin B i
vo chu trnh t bo, lm ng li cc gen RAG, v phn hy
cc protein ca gen ARG (Recombination Activating Genes; cc
gen hot ha ti t hp).
P r e c i p i n r e a c tio n ; P hn ng k t t a, m t k th u t nh
lng s s n x u t k h n g th. S lng k h n g th c xo

nh theo s lng cc kt ta nhn c vi s lng khrv

nguyn c"nh. Phn ng kt ta cng c th c dng

nh r ha tr khng nguyn v cc vng d tha khng th
hoc khng nguyn trong cc hn hp khng nguyn v khng

th.
P r e d n is o n e : L m t steroid tng hp c h ot ng k h n g

vim v km hm min dch, dng cha bnh t min bnh

ung th bch cu v x l thi ghp c tnh trong cy ghp m.
Pre-T-Cell receptor: Th th t bo tin T, thng l chui a
ca t bo tin T, cc c bo - T h ym ocyte th a y t h cho cc chui
p tron g giai on u ca s p h t trin ca t bo T tp hp li

thnh th th t bo tin T.
P r im a r y fo c u s ;

S hi t s khai, hi t s cp, ni v qu

trnh hot ha t bo B c hnh thnh vng bao quanh gia

cc vng cha t bo T v t bo B ca m lympho. y c s
tng tc gia cc t bo T v t bo T t t bo B c th
bit ha thnh t bo plasma tit khng th.

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P r im a r y f o llic le ; N an g s cp cha cc t bo B lu tr, l v
tr s h n h th n h cc trung tm m m v cc n a n g th cp.
P r im a r y im m m u n e r e s p o n s e : p n g m in dch s cp,
c th h i n khi gy m in dch s cp i vi m t k h n g
n gu yn .
P r im a r y in t e r a c t io n : S tng tc s cp, l s lin k t ca
cc p h n t k h n g th vi k h n g ngu yn , phn v it vi s tng
tc th cp (secondary interaction ) trong c h in tng k t
ta ca cc k h n g n gu yn ha tan hoc s n g n g k t ca cc h t
k h n g n g u y n .
P r im a r y l y m p h o id o r g a n : C quan lym pho s cp, xem c
quan lym p h o tru n g ng (Central lym phoid organ).
P r im in g : l^m mi, to mi. s to mi cho cc t bo lym ph o

S(f khai cha h lip xc vi khng nguyn s xy ra khi khng

ngu yn c trn h din cho ch n g d n g to ra p n g m in
dch. Cc t' bo c khi ng nh vy s b it ha th n h dng
t ho h iu qu (effector cells) hoc es bo ghi nh (m em ory cells)
c kh n n g to p ng m in dch th cp v p n g tip theo.

Pro-B-Cells: Cc t bo khi thy B, biu hin cc protein

ch th b m t, nh ng cha c s sp xp li cc gen chui nng.
P r o d u c t i v e r e a r r a n g e m e n t s : S sp xp li s n phm , m t
cliui th th b t k ca t bo lym pho c sp xp li th eo h ai
cch khc nhau; sp xp li sn phm v sp xp li k h n g to
r a s a n I^ h m . S ) X) l i s n p h r im l t o r a k h u n g c c h n h

xc di vi n il ih th Ihco yu cu.
P r o g o n it o r : N hnp t bo khi th y, l n h n g l bo
hit ha hn t t l)o niin ty xidiig (stem cells) Ihnh t n g
quan th cc t bo mu (! chn v m.at i kh n n g t bin i
ti li giVig n h t bo nfun ty xng.
P r o g r a m n ie d c e l l d e a th : C ht theo chng trnh, xom apoptosis.
P r o e r d in : Xem yu t' p, m t yu t th am gia vo qu trn h
hot ha b th theo con ng bn cnh (a lter n a tiv e p ath w ay).
P r o s t a g l a n d i n : L m t sn phm b in i ca lip it bt ngun
t ax it arach id on ic, c n h iu hiu qu i vi h n g lot m t
bo, bao gm cc h ot ng gy vim .
P r o t e a s o m e : Mt vi th bao gm n h iu tiu n v cha cc
protease th a m gia phn h y cc protein ni bo. Cc p e p tit ni

sinh b phn hy trong proteasome s c lin kt vi MHC-I

316
trn h d in k h n g n gu yn . H ai tiu n v ca p rotoa-som e c
cm ng vi in terferon (IFN) c m ha tron g cc m gen ci
M HC.
P r o t e c t in : (C D 59) l m t p rotein b m t t bo, gi p cho t
bo v t ch bo v khi tc dng gy tn thng c a b th . No
ngn cn vic h n h th n h phc h tn cng m n g (M AC) bnp
cch km hm s lin k t ca Cg v Cg vo phc h C-,b, Ce, C 7 .
P r o t e c t i v e I m m u n ity : T rnh m in dch, l s i kh n g
chng li n h im tr n g c hiu, gy n h im tr n g hoc tim
chng.

Protein A: Mt loi protin ca thnh t bo L cu vng

(S tap h ylococcu s aureus), lin k t c h iu vi Fe c a IgG, gi'
cho vi k h u n khi tc ng opsonin ha ca IgG v n g n cii 0011
ng h ot ha b th.
P r o t e i n k i n a s e C: (PKC) l m t h en zym se r in e / th ereon in o
k in a se c h ot ha bng d iacylglycerol v ion ca n x i. Q u trn h
h ot ha ny l k t qu ca s tru yn tn h iu nh n h i u th th
khc n h au .
P r o t e i n t i r o s i n e k in a s e : L en zym lm k t hp nh m pht
p h t vo cc gc tyrosine, c vai tr quan trng tro n g qu trnh
tru yn tn h iu v iu ha s sin h trng t bo. H ot n g ci
protein ty ro sin e k in a se li c iu ha bn g p rotein tyrosin c
p h o sp h a ta se.
P r o t o o n c o g e n e : G en tin ung th, l cc gen k im so t VI
iu ha qu trn h sin h trng. K hi cc gen nv b t b in s
gy b in d n g c tn h t bo, dn dn u n g th (xem th m oncogene).

Provirus; L mt dng ADN ca retrovirus khi ci vo genom

ca v t ch, n c th gi li s bt h ot p h in m l u di.
P - s e le c t in : Xem selectin .
P -T a: xem pre - T - cell 1-eceptor.
P u l m o n a r y s u r a c t o m t A a n d D p r o t e in s : C c p ro tein b
m t A v D c a phi l n h n g lectin h p en traxin c vai tr qu an
trn g tron g p ng m in dch pha cp.

Purin nuceotide phosphorylase (PNP) delciency: S

th iu h t purin n u cleo tit ph otp h p rylaza, s th iu h t n y g y ra
th i u h t m in dch c dnh, gy ra s tch ly p u rin n u cle o tit
gy c cho s p h t trin t bo T.

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P u s: M , l hn hp cc m nh v t bo v xc bch cu tru n g
tn h c m t cc vt thng v vim p xe (a b scesses) b nhim
k h u n n goi bo (v d cc vi k h un gy m xanh P seu d om on as
a(ruginosa).
P y o g e n i c b a c t e r ia ; Cc vi k h un gy m , l n h n g vi k h u n
c v bc ln gy, kh khn cho qu trn h thc bo k h i nh im vo
cc v t th n g th ng gy ra m . Cc vi k h u n n y thng gy
t v o n g cho tr nh v h in nay cn gy n h im tr n g m cho c
ngi gi.

Rulel2/23: Lut ny ni rng cc on gen ca khng th hay

th th t bo T c th c lin k t vi n h au ch n u m t on
c m t trn h t tn h iu n h n b it vi m t on cch gm 1 2 cp
b a se v on k ia cha m t on cch gm 23 cp b ase.
R a c: xem cc p h n t protein G nh (sm all G protein s)
R a d ia t i o n b o n e m a r r o w c h im e r a s ; V t ghp t y xng b
ch iu x, l cc con chut b ch iu x n n g v sa u c
ghp cc t bo tu xng ca m t dng ch u t khc, do cc t
bo bch cu s khc bit v m t di tru yn vi m i trng ch n g
p h t trin . N h n g con chut ghp ny c vai tr q u an trn g
trong n g h in cu s ph t trin cc t bo lym pho.
R a d io i m m u n o a s s a y (R IA ): X t ngh im m in dch ph ng x.
S t ng tc k h n g nguyn- k h n g th c th c n g h in cu
nh x t n g h im m in dch phng x trong k h n g n gu yn hay
k h n g th c nh du bn g hot ng ph ng x. M t k h n g
n g u y n h ay m t k h n g th kh ng n h du s c dn h vo m t
c h t h tr c n g ch n g hn nh b m t nha, v t l k h n g th
hoc k h n g n g u y n nh du c duy tr trn b m t s
c xc n h o s lin kt.
R af: xem cc p h n t protein G nh (sm all G protein s).
R A G : Cc g en hot ho s ti t hp R A G -1 v R A G - 2 m
ho cho p rotein R A G - 1 v R A G - 2 , y l n h n g p rotein qu an
trn g i vi s sp xp li cc gen th th. C hut th iu c hai
loi gen n y k h n g th to ra cc th th do vy k h n g c cc t
bo lym pho.
R a p a m y c in : (hoc sirolim us) L thuc c c h m in dch c tc
d n g loi b h o t ng ca ch t ti t t bo.

Ras: xem cc phn t protein G nh (small G proteins).

Rearrangement: S sp xp li, s b iu h in cc th

th
k h n g n g u y n i hi s sp xp li cc on gen tron g qu trn h

318
p h t trin lym pho. T rnh t v n g V c b iu h i n l to n n t
s sp xp li cc on gen.

Receptor editing; Sa i th th, s thay th ca mt chui

nh trong th th k h n g nguyn t phn n g trn t bo B cha
trng th n h b n g m t chui nh cha qua s t p h n n g c
gi l s sa i th th iu ny cng c x y ra vi chui n n g.

Receptor associated tyrosine kinase; Tyrosine kinase kt

hp th th. Cc th th k h n g ngu yn c a ly m p h o lin k t VI
th th lin k t tyrosin e k in a se th n h p h n c h n h c a h Src th
th n y lin k t vi ui th th k h n g n g u y n th n g qua cc
v n g S H 2 ca chn g.
R e c e p t o r - m e d i a t e d e n d o c y t o s is : Thc bo qu a tru n g gian
th th l s nu t vo trong cc th thc bo ch a cc p h n t
lin k t vi cc th th b m t. Cc k h n g n g u y n lin k t vi
cc th th t bo B c thc bo nh qu trn h n y.
R e c c e s s i v e l e t h a l g e n e s ; Cc gen ln g y c h t m ho cho
m t p rotein cn th i t cho ngi hoc ng v t p h t trin n tui
trng th n h . K hi c hai bn sao b th iu s t, ngi hoc ng
v t s ch t n gay tron g t cu n g hoc ngay sa u sin h .
T rong bt k trng hp m cc t bo hoc m c cy ghp,
ch n g s n t th cho v c cy vo tro n g t h n h n
(recepient) hay v t ch.

Recombination activating genes: Cc gen hot ho s li

t hp: xem R A G - 1 v RAG- 2 .
R e c o m b in a t i o n s i g n a l s e q u e n c e s _ R S S s: Cc trn h t tn
h iu t i t hp l cc on A D N ngn nm b n c n h cc on
gen c t i sp xp s n sin h m t ex o n v n g V. C h n g
lun ch a m t on by hoc on mi bo th p h n b i t n h au
nh 12 hoc 23 cp base. Cc on gen ch c t hp vi n h au
n u m t on n m cnh m t R SS cha on c ch gm 1 2 cp
b a se cn on k ia nm cn h m t R SS cha on c ch gm 23 cp
b a se_ quy tc 12/23 ca s ni ghp cc on gen .
R e d p u lp ; P h n t y l v n g k h n g lym p h o tron g l lch
cha cc t bo h n g cu b ph hu c gi l p h n tu .

Reed- Sternberg cells: Cc t bo Reed- Sternberg l cc t

bo B ln c tn h x u t h in tron g b n h u n g th H od gk in .

Regulator or suppressor T cells: Cc t bo T iu ho hay

p ch l cc t bo c th c ch p ng t bo T.
R e s p ir a t o r y b u r s t: S b n g n h hp. V ic cc t bo bch
cu tru n g tn h hoc i thc bo th u n h t c cc p h n c

319
o p so n in ho s kch thch bin di ch u yi ho trong t bo gi l
bng n h hp. iu ny s dn t('i s sa n xut h n g lot cc
c h t tru n g fan.

Respiratory syncytial virus (RSV): Virus hp bah h"p l

m t tc n h n gy l)nh (i ngi. N l m t n gu yn n h n gy bnh
ph biii ti'0 n g n h im v n g ngc trm trng tr em nh. thng
di kni vi kh th(. v c cc bnh n h n su y yu m in dch v
l)('iih n h n AIl^S.
R e v P r o t e i n l s n phm gen reu ca viru s gy su y gim
m iii dch ( ng i (hu m an im n iu n od cicien ry viru s HIV). I rotein
R('V n y s th c y s tru yn AKX vim .s l n h n ra l bo cht
trong qu trn h n lin ln ca virus.

Reverse transcriptase; Enzyme phin m ngc l mt

th n h phn cn th i t ca rctrovirus v n chuyn
tli iih A D N tric khi tcli hdp vo A D N ca t bo
sa<J chp niic (.nt cho ])hp cc trnh t AR X
th n h ADN' 1)0 su n g (com)l(Mnontary D N A c D N A ) ,
c l ch dnf v tr th n h mL tc n h n quan
sin h hc p h n t.

h gon ARN
ch. E nzym e
dc ch u yn
bi vy n
trn g di vi

Reverse transcriptase- polymerase Chain reaction (RTP C R ): P h n n g chui tr n g hp- cn zym e phin m ngc c
s d n g k h u ych di cc trn h t ARN. E nzym o p h in m
ngc c s d n g chuyn cc trnh t AR N th n h cc trn h
t A D N b su n g (cD N A ). n lt n s dc k h u ych i nh
PCR.
R h e s u s /R h b o o d g r o u p a n t ig e n ; K hng nguyn nhm m u
R h osu s l< m t k h n g ngu yn m ng t bo hn g cu c th thy
trn b m t t bo hn g cu ca kh K hesus. Cc k h iig ngu yn
cliVig l i Rh k h n g lm ng ng kt cc t bo h n g cu ngi,
do k h n g th ch n g li Rh c th ph t h in nh s d n g mt
])hp th C oom bs.

Rheumatic fever: Sl thp khp py ra bi cc khng th

dc kch th ch bi s nh im vi m t s loi S treptococcu s. Cc
k h n g th n y s k h n g cho vi cc k h n g n gu yn ca th n ,
khp v tim .
R h e u m a t o i d a r t h r it is : C hng vim khp d n g th p l m t
bnh s n g khp th n g gp c th do m t phn n g t m iii.
B nh n y li n qunn dn s sa n xu t cc n h n t thp klip, mt

;52U
k h n g th IgM chng IgG m c th c to ra trong cc )hii

ng min dch bnh thng.

S a n d v v ic h E L ISA ; K! th u t hnh kp ELISA s (iu khn

th lin kt vi b mt bt gi protoin hang cch

kt vi
opitope ca n. ^rotein c bt gi Iiy sau d s dc pht hiii
nh mt khng th lin kL enzymo c hiu cho mt t'pii()|n
khc trn b m t phn t protoin. iu n y to la ml ph|)

kim tra c tnh c hiu cao.

S c a t c h a r d a n a ly s is : P hn tch S catch ard l nil phn lch
ton hc s lin k t cn bng cho phi i lc v ho ti' cua s
tng tc ch t gn - th th c th c xc nh.
S c a v e n g e r r e c e p to r s : Cc th th th u dn k h n g nguyiH Cii
trn trn b mt cc di thc bo v cc t bo khc lin kl VI
h n g lot chiVt gn thi b (k h n g n gu yn ) v loi b ch n g l a
khi dng m u. Cc t bo Kuffei- trong gan c; bit c nh iu CU'

th th ny.
S C ID , scid: xem sovcro coiil)inocl immunoci(f'i(>ncy.

SDS- PAGE l tn vit tt thng gp ca din cii trn f(l

polvacrylamide (polyacrylamido gel okctrophoresis_ l^AGE) di
vi cc protein c ho tnn trong fht ty nalri dodecyl sulatt'
(sodium dodecyl sul'ato_ SD S). K thut ny dc s d n g rnt
ri d m t protein cc bit l sau khi clnli du v ngng k't
m in dch.

Secondary antibody response: Cc phn ng khii^ ih

th cp 1; phn ng k h n g th c cm ng do s lim lan Ui

hai hay tim tng cng khng nguyn tc l gy min dch th

cp (secon dary im m u n ization ). P h n n g

m in dch bc hai s

khi dng nhanh chng hn sau khi tim khng nguyn, t

c mc cao hn, c i lc cao hn p h n n g bc n h t v ch

yu l gmcc khng th IgG. Bi vy, phn ng i vi mi ln

gy min dch hi ttng ln v cng , v cc p ng ln th
h a i . th ba v n h n g ln tip sa u l c mc t n g dn.
S e c o n d s e t r e j e c t io n : T hi b b th cp. Khi th n h n ca

m hay c quan u tin loi b phn cy ghp th m ghp

th liai t cng mt th cho y s b loi b nhanh chng hn v
vi m t cng m nh hn n h iu . H in t ng n y c gi l s

thi b b th cp.
C o s t i m u l a t o r y s ig n a l; T n h iu n g kch th ch cn th i t
cho s h ot ho lym pho thng c gi l m t tn h iu cp h a i.
vi tn h iu th nht bt ngun t s lin k t k h n g n gu yn vc'i

321
m t th th k h n g n gu yn . C hai tn h i u n y u cn th i t cho
s h o t ho ca h u h t cc lym pho.
S e c o n d a r y i n t e r a c t io n s : Tng tc th cp (xem tng tc
s cp- prim ary in tera ctio n s).
S e c r e t o r y c o m p o n e n t : T hnh phn ti t c lin k t vi cc
k h n g th IgA tron g qii Lrnh tit ca c th l m t on cn li
c a th th poly- g lin k t vi IgA sa u kh i vn ch u y n qua t
bo b iu b.
S e l e c t e d ; M t t bo coi l c chn lc bi k h n g n gu yn
kh i cc th th ca n li n k t v k h n g n g u y n d. N u k t qu
l t bo bt u t n g sin h , th iu ny c gi l chn lc
dng, v t bo n y s to n n mt dng; n u k t qu ca vic
lin k t k h n g n g u y n l t bo b ch t th iu n y c gi l
chn lc dng m tn h h ay loi b dng.
S e l e c t in : L m t d n g lectin thuc h cc p h n t li n k t b
m t t bo ca cc t bo bch cu v cc t bo ni m m lin
k t vi cc phn ng trn phn t glycop rotein c cc c tn h
g in g m ucin.

Self antigens: Cc t khng nguyn (autoantigen). Cc

k h n g n gu yn tron g c th mi c th thng c gi l t
k h n g n gu yn . Cc t bo lym pho c p h n n g vi cc t
k h n g n gu yn tron g su t giai on cha trng th n h ca
ch n g , v n h n g t bao no thc s p h n n g vi cc t k h n g
n g u y n b ch t th eo chng trnh (apop losis).
S e l f t o le r a n c e : S d u n g np bn th n m t c th l s m t
ng i vi m t k h n g n g u y n khi k h n g n g u y n n y c to ra
bi c h n h cc m c a n. S dung np ny c gi l s t d u n g
np. X em thm s d u n g np (lolerance).
S e n s i t i z a t i o n ; T o ra n h y cm . Cc p h n n g d n g i hi
s gy m in dch trc hay l s to ra n h y cm i vi cc
ch t gy d ng kch thch cc phn ng nh y bn. Cc p h n ng
d n g ch xy ra cc c th d c nh y cm (se n sitiz ed ).
S e p s is : S n h im tr n g l s ly n h im vo dn g m u. H in
tng n y rt n g h im trn g v thng gy ch t, s l y n h im
vo dn g m u c a cc vi k h u n Gram m s khi ng shock
n h im tr n g do s gii p h n g ch t tit t bo T N F - a .
S e q u e n c e m o tif; M t m u trnh L l m t k iu cc n u cleotid e
hay cc a x it am in nm tron g cc gen hoc cc p rotein khc n h au
m th ng c n h n g chc nn g lin quan. Cc m u trn h t
quan s t th y tro n g cc peptid e lin k t vi m t glycop rotein

322
M H C c b i t l p h th u c v o y u cu i vi cc a x it a m in c

bit t c s lin kt vi phn t MHC .

S e r o c o n v e r s i o n : S c h u y n i h u y t th a n h l m t ph a c a
s l y n h i m k h i cc k h n g th ch n g l i t c n h n g y n h im l n
u ti n c p h t h i n ra tro n g m u.

Serology: Huyt thanh hc s s dng khng th kim tra

v o dc .:hnK n g u y n b n g cch d n g cc p h p th h u y t

thanh (seroloeical assays) uuc gi nh vy bdi v cc php th

n y b an u c ti n h n h vi h u y t th a n h , p h n dch cn li

mu ng, t cc c th c gy min dch.

Serotonin: Cht ha gii trung gian. Cc t bo ph chut
n h t ch a c h t h a g i i tru n g g ia n tan, k ch thc nh tron g cc

ht ca chng.
S e r o t y p e : T yp h u y t th a n h . Cc d n g vi k h u n k h c n h a u

cng nh cc tc nhn gy bnh khc i khi c th c phn

bit nh cc typ huyt thanh ca chng tc l kh nng mt
h u y t th a n h m in d ch lm n g n g k t h a y p h h u m t s ch n g

vi khuan ny ch khng phi l chng khc.

S e r p in ; l m t h ln cc c h t c c h p roteaza k i u serin .
S e r u m : H u y t th a n h l p h n d ch cn l i c a m u ng.
S e r u m s i c k n e s s ; m h u y t th a n h , h i n t n g x y ra khi

huyt thanh hoc protein huyt thanh ngoi lai c tim vo

m t ng i n o . H i n tng n y l do s h n h th n h cc phc

h min dch gia protein c tim vo v cc khng th c

h n h th n h ch n g l i n. i u ny c m t qua st,

bnh than v vim thn.

Severe combined immune deficiency (SCID): Suy gim
m in dch k t hp n g h im trn g l m t b n h su y g i m m in dch

trong c khng th ln p ng t bo T u khng c. iu

n y th n g l k t qu c a s th i u h t t bo T. t b in s c id

cng to nn bnh ny chut nht.

SH2 domains: Vng SH2 xem cc tyrosine kinase h Src.
Khp tn hiu (signal joint) c to ra nh s ni kt chnh xc
c a cc tr n h t tn h i u n h n b i t tro n g qu tr n h t i t hp

sinh dng lm sn sinh cc th th t bo T v cc gen khng

th.
Signal transducers and activators of transcriptions
(STATs): Cht cm ng tn hiu v hot ho sao m (xem kinase
Janus)

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S i g n a l t r a n s d u c t i o n : S dn tru yn tn h iu m t qu trn h
(,h u n g tron g cc t bo n h n c s bin i tron g mi
I rng ca ch n g . T i cc t bo lym pho. n h n g s b in i qu an
tr n g n h t l n h n g b in i xy ra tron g qu trn h l y n h im
lm s n sin h k h n g n g u y n kch th ch cc t bo c a h thVig
m in dch t o ra p n g m in dch th u c.
S i n g l e c h a i n F v f r a g m e n t : o n n c h u i F v 0 ch a m t
v n g V c a c h u i Iic n g c l i n k t b n g m t o n p e p t i d e t n g

hp ko di vi v n g V ca m t chui n h c th c to ra b n g
k th u t di tru y n .
S i n g le - p o s i t i v e t h y m o c y t e s : Cc t bo tu y n c dng
tn h n. T ron g qu trn h trng th n h c a t bo T tu y n c.
cc t bo T tr ng th n h c n h n b it b n g s b iu h i n ca
c CD4 v n g th th C D 8 , do vy c h n g c gi l cc t
b o tu y n c d n g tn h n
S ir o lim u s ; L m t tn thu c dc ch"p n h n i vi c h t ho
hc rap am ycin ; c h a i tn ny u c th dc d n g h on i cho
Iihau tron g cc v n bn.

SLC: Cht tit ho hc c tn SLC c sn xut bi mch

bch h u y t, c tc d n g th u h t cc t bo tu a.
S m a ll G p r o t e in s : C c p r o t e i n G n h l cc p rotein n
ph n ch n g h n n h R as, c h n g h ot n g n h n h n g p h n t
tn h i u ni bo dc th e o r t n h i u s k in tn h i u x u y n m n g.
S m a llp o x : B n h u m a l m t b n h ly n h im gy ra bi
v iru s u m a (v iru s variola), n t n g g i t c h t ti 1 0 % ngi
m c bnh. N g y n a y n b loi b h on ton nh tim ch n g.
S o m a t i c d i v e r s i c a t i o n t h e o r y : T h u y t s a d n g ho th
sin h dng (th som a). K hi cc nh m in dch hc p h t h i n ra
k h n g th l b in i, h lu n bn n h iu g i th u y t k h c
n h au tron g c t h u y t s a d n g h o s i n h d n g cho r n g
cc g en m ha cho cc p h n t k h n g th l k h n g th a y i
n h n g c h n g c a d n g ho tron g cc t bo sin h dng. iu
ny n g m t p h n v h in nay cc si u t b in tron g t bo
sin h dng c n g h i n cu r. T uy n h in cc gi th u y t k h c
c n g cn c gii th ch cc c tn h k h c c a s a d n g
k h n g th , bao gm s s p xp l i cc g en v s c h u y n i cc
d n g t ng ng.
S o m a t i c g e n e t h e r a p y : L iu p h p gen sin h d n g (xem liu
php gen).

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S o m a t i c h y p e r m u t a t io n : S i u t b i n sin h dng. T rong
p n g t bo B vi k h n g th , cc tr n h t A D N v n g V tri

qua qu trnh siu t bin sinh dng, kt qu l to ra th

h cc k h n g th bin i, mt s" trong s li n k t vi i lc
cao i vi k h n g n gu yn . iu n y cho p h p i lc c a k h n g
th t n g ln . Cc t bin ny ch tc n g ln t bo sin h d ng
v k h n g c di tru yn qua t bo sin h dc.
S o m a t i c r e c o m b in a t io n : Ti t hp sin h dng. T ron g qu
trn h p h t trin ca lym pho. cc on gen th th tri qua qu
trn h t i t h p s i n h d n g to ra cc exon v n g V n g u y n vn
m ho cho v n g V ca mi phn t k h n g th v cc ch u i th
th t bo T. N h n g s kin n y ch x y ra cc t bo sin h
dng v n h n g bin i ny l kh n g di tru y n .
S p a c e r : on cch: xem lu t 12-13.
S p e c iA c it y : T n h c h i u ca m t p h n t k h n g th q u y t
nh k h n n g p h n b it i vi ch t sin h m in dch c a n vi
cc k h n g n gu yn khc.

Spectratyping; Ngi ta s dng k thut nh kiu ph

d xc n h cc k iu on gen A D N n h t n h ch o ra m t s cch
qu ng lp li ca 3 n u cleotid e hay m t codon.
S p le e n : L lch, l mt c q u an nm p h a trn bn tri ca
k h o an g m n g b n g cha m t tu li n q u a n n v ic loi b
cc t bo m u gi ci v m t tu trn g li n q u a n n cc t bo
lym pho p n g i vi cc k h n g n g u y n c v n c h u y n ti l
lch b n g ng m u.

Src- family tyrosine kinases: Cc tyrosine kinase h Src

l cc p rotein ty o sin e k in a se lin k t vi th th . C h n g c m t
s' v n g c gi l v n g tng ng- Src 1 , 2, 3. V n g S H l cha
v tr h o t ng ca k in a se, v n g S H 2 c th lin k t vi gc
p h o sp h otyrosin e, v v n g S H 3 li n q u an n n h n g t ng tc
vi cc v n g giu proline trong cc p h n t p ro tein khc.

Staphylococcal enterotoxins (SEs): Ni c t ca

S t a p h y l l o c o c c u s , gy n n ng c thc n v c n g k ch th ch
cc t bo T lin k t vi cc ph n t ca M H C lp II v v n g Vp
ca n h n g th th t bo T nht n h, c h n h v v y cc ni c t'
Sta p h yllococcu s l cc siu k h n g n gu yn .

STATs: xem cc kinase Janus.

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S t e m - c e l l f a c t o r (S C F ): N h n t t b o g c l m t protein
x u y n m n g t r n t

b o n n t u x n g l i n k t v i C - K it , m t

t h t h t n h i u c t c n g l n s ) h t t r i n t b o B v c c t

bo bch cu khc.
S t r o m a l c e lls : T bo nn s ph t trin c a cc t bo lym pho
B v cc t bo lym p h o T din ra di s tng tc vi cc t b o
n n c va i tr cu n g cp cc tn hiu khc n h au c tn h ch t tan
v lin k t t bo i vi s ph t trin t bo lym pho.
S u b c u t a n n e o u s la y e r ; Cc kh ng n gu yn c th c tim
vo bn tron g t n g d i d a cm ng m t p n g m in dch
th u c (Xem in tra cu ta n eo u s).
S u p e r a n t i g e n s : C c s i u k h n g n g u y n l cc p h n t
kch th ch m t tp con cc t bo T bn g cch lin k t vi cc
p h n t M HC lp II v v n g v p ca nh ng th th t bo T qua
kch th ch s h ot ho cc t bo T c b iu h in cc on gen
V(3 c b it. Cc ni dc t S tap hyllococcu s l m t tron g cc
ngun si u k h n g n gu yn .

Suppressor T cells: Cc t bo T p ch. (Xem cc t bo T

iu ho- reg u la to r T cells).
S u r f a c e im m u n o g l o b u l in (slg ): Cc k h n g th b m t. Cc
p h n t k h n g th lin k t vi m ng m h o t ng n h th th
k h n g n g u y n trn cc t bo B thng dc gi l cc p h n t
k h n g t h b m t.
S u r r o g a t e l i g h t c h a in : C h u i n h i d i n c to nn t
h ai p h n t c tn l V pre-B v 5 . C ng lc, chui ny c n g c
th b t cp vi m t chui n n g cu trc, ch n g s di ch u yn ln
b m t t bo v bo tn hiu cho s p h t trin ca t bo pre-B.
S w i t c h r e g i o n o f D N A : V n g A D N c h u y n i, kh i s
ch u y n i cc iso ty p e xy ra, exon hot ng v n g V ca chui
n n g tri qua s ti t hp sin h dng vi m t gen v n g c nh
3 c a m t v n g A D N c h u y n i; s lin k t A D N ny k h n g
n h t th i t phi x y ra cc v tr ch n h xc bi v ch n g x u t
h in tron g v n g A D N intron. do t t c cc s ti t hp
ch u y n i ny u c to ra.
S y k ; Xem ty ro sin e k in a se .

Sympathetic ophthamia; Khi mt mt b tn thng th

th ng c m t c p h n n g t m in lm ph h u m t kia y l
hi ch n g c gi l b n h ng cm n h n cu.

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Syngeneic graft: Cy ghp ng gen

l s cy ghp gi;i
h a i c th h on ton ging n h au v m t di tru yn . S cy ghp
n y c chp n h n nh cy ghp ch n h n.

Systemic anaphylaxis: Phn v h thng l dng nguy

h im n h t c a p h n ng qu m n tc thi. N lin q u an n vie
k h n g n g u y n tron g dng m u kch th ch cc t bo ph trong
to n b c th . S h o t ho cc t bo ph n y s gy nn s gin
m ch, tch lu dch m, lm s n g th a n h qun v thng gy
ch et.
S y s t e m i c l u p u s e r y t h m a t o s u s (S L E ): B n h L u p u t b a n
h t h n g l m t b n h t m in tron g cc t k h n g th chn
l i A D N v p rotein lin k t vi ax it n u cleic s to n n cc phc
h m in dch lm ph hu cc m ch m u nh c b it l cc
m ch m u c a th n .
T ly m p h o c y t e s ; C c t b o T h ay lym p h o T l m t tp con
c a cc t bo lym pho m c im ca ch n g l s p h t triii
d in ra tu y n c v m an g cc th th lng d p h n t o
li n k t vi cc p h n t protein ca phc h C D 3 . H u h t cc t
bo T ch a th th lng d p h n t a;|3 n h n g cc t bo T .

l i cha th th l ng d phn t . .
T r a n s m e m b r a n e a c t i v a t o r a n d C A M L - i n t e r a c t o r _ TAC I:
C h t h o t h o x u y n m n g v c h t t n g t c C A M L l
th n h v in c a h th th T N F v l m t tron g h a i nhm th th
ch n h ca BLyS. N c tm th y trn cc t bo B, cc t bo c
tua, cc t bo T v c th l m t th th quan tr n g nhn cc
tn h iu t B L yS.

Tacrolimus hay FK506: l mt dc cht polypeptit c ch

m in dch. N s bt h ot cc t bo T b n g cch c ch s dn
tru y n tn h i u t th th ca t bo T n y. T acrolim u s v
cy closp orin g l n h n g ch t c c h m in dch ph b in n h t trong
c y gh p m.

Transporters associated with antigen Processing (TAPl

and TAP2): Tc nhn vn chuyn mnh peptit khng
nguyn lin kt vi qu trnh ch bin khng nguyn l
cc p rotein b n g t lin k t A T P lin q u an n v ic vn ch u yn
cc loi p e p tit k h n g n g u yn t t bo c h t vo k h o a n g ca li
ni ch t, t i y c h n g s lin k t vi cc p h n t M HC lp I.
T A P - a s s o c i a t e d p r o t e i n (T a p a s in ): M t d n g P rotein lin
k t vi T A P c v a i tr q u an trn g tron g s lp gh p p e p tit k h n g

327
n g u y n vi cc p h n t MHC lp I; n u t bo th i u protein
'T apasin n y th phn t M HC lp I s km bn trn b m t t
b o,

Antigen- binding target cells: Cc t bo ch lin kt vi

k h n g n gu yn . Chc n n g ca cc t bo T tc n g l lu n lun
k im tra s th a y i m ch n g to ra trn cc t b o c h lin
k t k h n g n g u y n Cc t bo ny c th l cc t bo B c
h t ho s n x u t ra k h n g th; i thc bo c h o t
h o g it vi k h u n hoc cc t bo kh u; h a y cc t bo
'o n h d u m b git bi cc t bo T gy c.
P r o t e i n T at: l s n phm gen ta t ca HIV. N c to ra k h i
c c t bo n h im tim n b h ot ho. N s li n k t vi m t tc
n h n t n g cng sao m nm trong on di lp li t n c n g ca
p roviru s, qua lm t n g cng s sao m ca h gen tin viru s.
T- c e l l c lo n e : M t d n g t b o T l m t tp hp cc t bo
x u t p h t t m t t bo T b an u.

T*cell hybrid: Cc t bo lai T l cc t bo c hnh thnh

t n g cch d u n g hp m t t bo T c h o t ho c h iu
k h n g n gu yn vi m t t bo T ca m u bch h u y t. Cc t bo
la i ny s cho ra th th ging nh t bo T c h i u to n n
'chng v l i c k h n n g sin h trng c trn m i trng nui
<cy ging nh t bo khi u.

T-cell line: Dng t bo T l dng cc t bo nui cy T sinh

trng c do cc chu k kch thch lp l i th n g l nh k h n g
n g u y n hoc cc t bo trn h din k h n g n gu yn . K hi t n g cc t
bo T n l t n h n g dng ny c n h n ln ch n g s to ra
m t dng t bo T v tnh.

T-cell receptor (TCR): Th th t bo T l mt

h etero d im er ca cc chui siu bin a, p lin k t vi n h a u b n g
lin k t d isu lid e c biu h in trn b m t m n g t bo nh
m t phc h vi cc chui CD3 k h n g b in i. Cc t bo T
m an g k iu th th ny th n g c gi l cc cc t bo Ta:p.
M t k i u th th khc c to nn t cc chui bin i Y v 5
Cng b iu h in vi C D 3 trn m t qun th t bo T. c h a i loi
th th n y u c biu h in c n g vi m t h om od im er gm h ai
'chui li n k t d isu lfid e vdi nhau.
T - c e ll z o n e : V n g t b o T trong cc m bch h u y t ch a rt
n h iu t bo T v khc b it h n vi v n g t bo B v cc n h n t
nn.

328
T e c - k in a s e : S h ot ho cc th th k h n g n g u y n t bo
bch cu c k t hp vi s h ot ho PLC-y th n g qua cc
th n h v in c a h T e c - k in a s e thuc vo cc k in a se ging src.

Cc Tec-kinase khc l Btk cc t bo B b t bin trong

bnh thiu ht min dch ngi, bnh agammaglobulinemia
lin kt nhim sc th X (X- linked agammaglobulinemia XLA)
v Itk bch cu T.
T e r m in a l c o m p l e m e n t c o m p o n e n t : H th n g b th c th

c hot ho trc tip hoc nh khng th, nhng c hai con

ng n y u dn ti s hot ho cc t h n h p h n b t h c u i
c n g dn ti s hn h th n h phc h tn cn g m ng.

Terminal deoxylnucleotidyl transferase (TdT); Enzym(

transerase deoxylnucleotidyl cui cng s chn cc nucleotid
khng theo mu hay N-nucleotide vo trong cc v tr ni gia
cc on gene ca th th t bo T v cc gene vng V ca phn
t immunoglobulin. Cc N-nucleotide ng gp rt ln ng g[)
rt ln vo s a d n g lin k t ca cc v n g V.
T e r t ia r y r e s p o n s e ; p n g b c b a . Khi m t k h n g n g u y n
c tim li ln th ba, phn ng p n g s c gi l p
n g b c b a v s n h im ny l q u t r n h m i n d c h h o c p
b a (tertia ry im m u n iza tio n ).
THI cell: Cc t bo THI l mt phn nhm ca cc t bo T

CD+ phn bit nh cc cytokine m chng sn xut. Chng

lin quan ch yu n vic kch thch cc i thc bo v i khi
c gi l cc t bo TC D 4 gy vim .
T H 2 c e ll: C c t b o T H 2 l m t p h n n h m c a cc t bo
T CD 4 p h n b it nh cc cytok in ee m c h n g s n xu t. C hn

ch yu lin quan n vic kch thch t bo B sn xut khng

th , v th n g c gi l l cc t bo TCD 4 tr gip.
t H S c e ll; K hi n im c c t b o T H 3 c s d n g m

t cc t bo c nht c kh nng to ra ch yu nhn t"gy

bin dng sinh trng p trong p ng i vi khng nguyn.
Chng pht trin u th trong p ng min dch th dch
vi cc khng nguyn c tip xc qua ng ming.
T h o r a c ic d u c t: H ch bch h u y t t h u h t cc p h n tron g cr

th tr phn u, c v tay phi, c tp trung vo mt mch

bch h u y t ln, m c h n g c , m ch n y ch y so n g so n g vi n g

mch ch ti phn ngc v vo mch mu di n. Mch

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nj(c ny do vy s dn cch bch Im yt v cc t bo bch cu

lympho quay tr li vng tun hon mu.

Thymectomv; S ct b tuyn c bng phu thut.
T h y m ic a n la g e : C c n g u y n b o t u y n c l m t m t
vung nn lu y n c s ph i trin trong qu trnh p h t trin phi.

(Xem thymic stroma).

T h y m ic c o r t e x ; V n g v t u y n c l v n g ngoi ca mi
kne tu yn c trong cc t bo tuyii c s kh ai s sin h si, ti
Siip xp l i cc gene th th l bo T ca chng v tr i qua mt
(|n trn h chn lc tuyn c, c bil l chn lc dng tn h i
V('(i cc t bo biu b v tuyn c (thym ic cortical ep ith e lia l
cclls).
T h y m ic s tr o m a ; C h t n n t u y n c cha cc cht nn t
bo cha cc L bo bieu b v cc m lin kt h iih thn h nn
lit \ 1 inui 11
cii tliit cho s pht Irin ca t bo T.
T h y m o c y t e s : C c t b o t u y n c l cc t bo lym pho T
tm th y lu y n c. chng clia ch yu l ce l bo T dang
phL trin, rig mt s t bo tu yn c hon ton trng

thnh v mt chc nng.

T h y m u s ; T u y n c la IKH din ra s pht trin ca t bo T.

l mt c quan biu m lympho pha trn ca gia ngc,

ngay pha sau xng c.
T h y m u s - d e p e n d e n t a n tig e n s

(T D

a n tig e n s ).

Mt s'

khng nguyn s kch ihch cc dp ng ch cc c th c t bo

T; ch n g c gi l cc k h n g n g u y n p h t h u c t u y n c.

Cc khng nguyn khc kch thch s sn xut khng th khi

vng m t t bo T th o Ri L cc k h n g n g u y n k h n g

ph thuc tuyn c (thymus- independent antigens_ TI

antigcns). C hai dng khng nfuy{'n Ti, TI- 1 c hot tnh kch
thch t bo T t bn troiiR v TI- 2 c l en kha nng hot ho t
bo l bng cch c Iihiu cpitope ins nhau lin kt cho vi
cc th th t ho B.
( c t bo T v lym |)ho 'I' l cc m La ngn gn cho cc t b o
ly m p h o p h t h u c t u y n c v qun th lym pho n y s kh n g
th p h t trin nu thiu mt tuyn c h ot ng.
T im e - l a p s e v i d e o m ic r o s c o p y : Ngi ta s d n g k n h h in

vi ghi hnh tng khong thi gian kiem tra cc qu trnh sinh
hc t cc qu trnh nhanh nh s di ch u yn ca t bo n cc
qua Irnh chm nh s n hoa.

T i n g i b l e b o d y m a c r o p h a g e ; T rong qu trn h h n h th n h
tru n g tm m m x u t h in cc t bo c gi l i t h c b o
t h b t m u . Cc t bo thc bo ny s nu't cc t bo B ch t
th eo chng trn h c to ra vi s lng ln tron g su t qu
trn h p n g ca tru n g tm m m .
T i s s u e d e n d r i t i c c e ll: T t c cc t bo c tu a x u t p h t t
m t t bo gc to m u s di c ti rt n h iu v tr kh n h a u t rn
k h p c th. Bi vy ch n g c gi l cc t t o t u a m .
T i s s u e g r a ft: S cy ghp cc c quan h ay c y m ch n g hn
nh cy ghp c s dng trong y hc sa cha cc tliiu
s t ca c quan hay m.
T i s s u e s p e c i l c a u t o im m u n e d is e a s e : M t s b nh t nn
t n cn g cc m n h t nh, ch an g h n vo t bo p c a tu d;io
L a n g erh a n s trong bnh tiu ng t m in; cc bnh d n g ny
c gi l b n h t m i n c h i u m .
T ite r : P h p c h u n k h n g h u y t th a n h l m t php (to

nng ca cc khng th c hiu da trn s pha long hiiyt

t h a n h t i i m CUI c n g c h n g h n m t m c b i n i n h t n h

trong kim tra ELISA.

T o ll- lik e r e c e p to r : T L R l- 1 0 (xem cc th th gin g Toll).
C c t b o ly m p h o T (T lym phocytes): Xem t bo T (T cells).
T N F ; Cc ch t c ca t bo lym pho (lym p h otoxin ), tc nhn
h oi t k h i u a (tum or necrosis actor- a).
T N F r e c e p t o r _ T N F R : C m t s cc th n h v in trong h cc
t h t h T N F M t s dn ti s ch t th eo chng trn h ca t
bo b iu h in ch n g (TN FR -I, II, Fas). trong khi n h n g Lh th
kh c l i d n ti s hot ho (CD 40, 4-1 BB). T t c n h n g th
th ny ch u yn tn hiu nh l cc protein bc ba.

Tolerance; Dung np min dch l s in.t dp ng min

dch vi mt khng nguyn. H Ihnp min dch l dung np
vi cc khng nguyn ca chnh n. S dung np i vi khng
nguyn ca bn thn l mt c im thit yu ca h thng
m in dch. Khi s d u n g np ny b m t i, h th n g m in dch c

the ph hu m ca chnh n gihg nh xy ra trong bnh t

min.
T o ll p a th 'w a y : C o n n g T o ll l m t con ng tn h iu r
in kch hot nhn L phin ni N F X n b;'in< ccli ph hu cht
c c h c a n I X B.

331
T t c cc th n h vin ca h Toll cc th th c p h t h in
cho ti n a y l ging vi h Toll ca D rosophila. C hng c t
tn l cc t h t h g i n g T o ll (Toll- like receptor-TLR) v nh s
n g sa u , c h n g hn th th ging Toll 4 hay TLR-4.
P a l a t i n e t o n s il; A m idan vm m in g nm c h ai pha ca
h u . N tp tru n g mt lng ln cc t bo lym pho c sp xp
n h l m t p h n ca h th n g m in dch k t hp vi rut hay
m n g n h y.
T o x ic s h o c k s y n d r o m e : Hi chng sc c t l m t phn
n g c t h th n g gy ra do s sn xu t m t lng ln cytokin e e ca cc t bo TCD4 b h ot ho bi siu k h n g n g u y n vi

khun, chng hn c t- 1 gy hi chng sc c t (TSST-1) do

S ta p h y llo c o c c u s a u reu s ti t ra.
Cc c t" b b(it hot c gi l c t g i m l c (toxoid)
th k h n g cn c na nh ng vn duy tr tn h sin h m in dch do
d ch n g c th c s dng gy m in dch.
T|(l; xem cc t b o T i u h o (regulatory cell).

TNF receptor-ass.ociated factors -TRAFs: Cc nhn t' lin

k t vi th th T N F l m t h protein bao gm t n h t l su
th n h v in n h iu th th h T N F khc n h au (T N F fam ily receptors_ T N F R s). C hng chia s mt v n g c gi l v n g TRAF,
v ng vai tr quan trng nh l tc nhn ch u y n i tn h iu
gi a p h a trc l cc th n h vin ca h T N F R v pha di l
cc n h n t p h in m.
T r a n s c y t o s i s : S vn ch u yn tch cc cc phn t qua cc t
bo biu b c gi l x u y n b o . S xu yn bo ca cc p h n t
IgA lin q u an n s vn chuyn xu yn qua cc t bo biu m
rut Irong cc n an g bt ngun t b m t n<in v bn v ho
nhp vi b m t nh khi tip xc vi khon'; rut.
T r a n s f e c t i o n : S t i n p . S a cc m an h nh A D N vo
trong t bo c gi l s c h u y n n h i m N u A D N n y c
biu h i n m k h n g cn phi kt h(p vi A D N ca t bo ch th
h in t ng n y dc gi l s chuyn n h im ch u y n tip , nu
AD N n y k t hp vi A D N cua t bo ch k h i n n h n ln
c n g vi s n h n ln ( ua ADX t bo ch qua to n n s
ch u y n n h im n dnh.
T r a n s g e n e s i s ; S tru ycn gen. ('c gen n goi lai c th ch n
vo h g en c a t bo chut bng q u t r n h t r u y n g h p g e n .
Q u trn li n y s to ra cc con chut ch u yn ghp gen e s d ng

332
t r o n g n g h i n c u c h c n n g c a g e n e c c h i i v o h a y g e n e
c h u y n g h p v s i u h o g e n e .

T r a n s lo c a t io n ; C huyn on nhim sc th . M t s b n h ung

th c cc c h u y n o n n h i m s c t h trong d m t on

nhim sc th c ni mt cch bt thng vi mt nhim sac

th khc.
T r a n s p la n t a t io n ; S cy ghp m hay c quan l c th ny
vo c th khc c gi l s g h p m . C q u a n c y g h p

(transplanted organ) hay m ghp c th b loi b do h thi

min dch tr khi c th nhn dung np vi cc khn^
nguyn ca m ghp hay cc thuc c ch min dch c s
dng chng li s loi b ny.
Transporters associated with antigen Processing - TAP:
X e m T A P l v T A P 2 : Tc nhn vn ch u y n lin k t vi qu

trnh ch bin khng nguyn

T u b e r c u l in te s t: Php th lao/tu berculin l mt php thi

lm sng trong mt dn xut protein tinh ch (purified protein d erivative_ PPD) ca M ycoh acterium tuh ercu losis. tc nhii

gy nn bnh lao, c tim di da. PFD kch thch mt dn^

phn ng qu mn mun c th no b nhim bnh lao hay
vi cc c th c min dch vi n.
T u b e r c u l o id le p r o s y : B nh lao hi: xem bnh hi
T u m o r im m u n o lo g y : M in dch ung th l m n hc nghiti

cu kh nng bo v ca vt ch chng li cc khi u thng s

d ng phng php cy ghp khi u.
T u m o r n e c r o s i s fa c to r - a : Yu t h o i t k h i u a l mt
cht ti t ca t bo c s n x u t bi i thc bo v cc t bo
T. N c n h iu chc n n g trong p ng m in dch. y l mt

thnh vin chnh thc ca h cc cht tit t bo TNF. Cht tit

ny hot ng nh l protein tit hoc protein lin kt t bo c
c h c n n g t n g t c v i c c th th th u c h c c t h

t h Lc

nhn hoi t khi u, cc th th ny n lt n s tng tc vi

cc p h n bn trong ca t bo th n g qua cc th n h phn TR A Fs

(tumor necrosis factor receptor- associated factors).

Tumor necrosis factor- P: Yu t hoi t khi u P( xem
c t ly m p h o ( l y m p h o t o x i n ) .

Cc khi u c ghp vo trong tli nhn ng en c th sin h

trng tip tc hoc b loi b th n g qua s n h n b it c a t bo
T i vi cc k h n g n g u y n c y g h p c h i u k h i u (tu-

333
mor- sp eciic tran sp la n ta tio n a n tig e n s_ TSTA) h a y c c k h n g
n g u y n lo i b k h i u (tum or rejection a n tig en s). TSTA l cc
peptid e c a t b in hoc cc protein t bo biu h i n qu m c
lin k t vi cc phn t MHC lp I trn b m t t bo khi u.

TdT- dependent dUTP- biotin nick end labeling: Php

t h T U N E L n h n bit cc t bo ch t theo chng trn h t i ch
nh cc on c trng trn A D N ca chn g. d U T P gn vi
biotin c thm vo u 3 t do trn cc m n h A D N nh enzym e TdT c th c n h n b it b n g nhum ho hc m m in
dch vi strep ta v id in lin k t vi enzym e.

Two- dimensional gel electrophoresis: in di gel hai

c h i u , cc protein tch n h au ra nh tp tru n g n g in theo
m t ch iu , tip l in di SD S- PAG E trn m t bn gel d n g
tm o m t gc ph hp th eo ch iu ban u. Phng php ny c
th tch v n h n bit m t lng ln cc protein k h c b i t n h au .

Type 1 hypersensitivity reactions: Cc phn ng qu mn

ty t 1 c p h n loi theo c c h ca chng: Cc p h n n g q u
m n t y p 1 lin quan n k h n g th IgE kch th ch cc t bo
pli; Cc p h n n g q u m n t y p 2 (typ 2 h y p e r se n sitiv ity reaction s) li n quan m k h n g th IgG ch n g li cc k h n g
n gu yn ni ch t hay b m t t bo; Cc p h n n g q u m n
t y p 3 (ty p e 3 h y p e r se n sitiv ity reaction s) lin q u an n phc h
k h n g n g u y n k h n g th; Cc p h n n g q u m n t y p 4 (type
4 h y p e r se n sitiv ity reaction s) l qua tru n g gian t bo T.

Tyrosine kinase; Enzyme tyrosine kinase l mt enzyme c

kh n n g phosphoryl ho c h iu cc gc ty ro sin e tron g p h n t
protein. C h n g rt quan trng trong vic h ot ho cc t bo
lym pho T v B. Cc tyrosin e k in a se q u an trng i vi s h ot h
t bo B l Blk, Fyn, Lyn v Syk. Cc tyrosin e k in a se quan trng
i vi h o t ho t bo T l Lck, Fyn, ZAP-70.
U r t ic a r ia : N i m y ay l m t th u t ng k th u t gi
ch ng p h t ban, tc l da b v ng a gy n n bi p h n n g d
ng.
N - t e r m i n a V d o m a n : V ng b in i tron g chui polypeptide c a m t phn t k h n g th hay th th ca t bo T c
to n n bi m t v n g V c u t n c n g N n l. Cc v n g V
bt cp s h n h th n h nn v tr lin k t k h n g n g u y n ca ph n
t k h n g th v th th t bo T.

334
V g e n e s e g m e n t s : Cc m nh gen V .95 axit a m in u tin ca

cc vng V trong phn t khng th hay th th t bo T c

m ho bi cc o n g e n V di tru y n c C r t n h iu don

gen V khc nhau trong h gen ca dng t bo sinh dc. to

ra mt exon hon chnh m ho cho mt vng V, mt on gen V
ph i c sp xp li lin k t vi m t on g en J hoc D J

c ti sp xp.
Vaccination: Tim chng l s trnh din c cn nhc to
min dch tp nhim i vi mt tc nhn gy bnh bng cch
tim vaccine l tc nhn gy bnh b lm yu hoc cht
(khng cn kh nng gy bnh).
V a le n c e : H o tr ca m t k h n g th h ay m t k h n g n g u y n l

s cc phn t khc nhau m n c th lin kt ti cng mt thi

im.
V a r ia b ilit y : T nh a dn g c a m t p h n t p ro tein l thc

o s khc nhau gia cc trnh t axt amin ca cc dng khc

n h au ca p h n t . Cc protein a d n g n h t c b it n It

cc khng th hay cc th th ca t bo T.
Variable region - V region: Vng bin i ca mt phn t
khng th hay th th t bo T c hnh thnh bi cc vng tn
cng amino ca cc chui polypeptide thnh phn. Cc vng ny
c gi l cc v n g b in i (variab le region - V dom ain ) v l

cc phn bin i nhiu nht ca phn t. Chng cha cc v tr

lin kt vi khng nguyn.
Vascular addressin; Cht kt dnh mao mch. Cht ch nh
vng mch l cc phn t trn t bo ni m m cc phan t lin
kt bch cu s bm vo . Chng c vai tr cha kho trong
vic xc nh v tr c trng ca bch cu trong c th.
V a v : xem cc p h n t protein t ng thch (adap tor p rotein s).
V (D ) J r e c o m b in a s e ; E n zym e li n k t cc m n h gen c a cc
gen th th t b B, T c gi l. N c to th n h t m t s

enzyme nhng quan trng nht l sn phm ca gen hot ho

en zym e ti t tp RAG - 1 (recom b in ase - a c tiv a tin g gen e) v

RAG- 2 m sn phm protein ca chng, RAG- 1, RAG- 2 c

biu hin trong qu trnh pht trin ca lympho v to nn hp
phn c hiu lympho duy nht c bit ca enzyme ti t hp

V(D)J.

V (D )J (V (D ) r e c o m b in a t io n ) : Q u trnh ti t hp c tm

thy ch cc t bo lympho ca ng vt c xng sng, n ch

p h p s t i t hp li cc m n h g e n k h c n h au th n h m t trn h

335
t m ho chui p olyp ep tid e hon ch n h c a p h n t k h n g th
hoc th th t bo T.

Very late antigens VLA: Cc khng nguyn rt mun l cc

th n h vin h Pi cc tc n h n hp n h t lin quan n tng tc
t bo- t bo v t bo- c h t nn. M t s" VLA c n gh a qu an
trn g i vi bch cu v s di c ca lym pho.
V e s s ic le s : Cc bng m n g l cc t i nm tron g t bo ch t,
c bao bc bi m ng
V ir a l e n v e lo p e : v bc viru s. N h iu loi viru s s n sin h ra bi
cc t bo n g v t c v c bc trong l p v v i r u s ca protein v lipid m n g t bo ch lin k t vi li v iru s b n g cc protein v viru s.

Virion: L cc tiu phn virus hon chnh m trong hnh thi

ny v iru s la n tru yn t t bo ny sa n g t bo k h c hoc t c
th n y sa n g c th khc.
V ir u s: L cc tc n h n gy bnh cu th n h t m t h gen a xit
n u cleic bc tron g m t v protein. C h n g ch c th n h n ln
tron g m t t bo sn g v ch n g k h n g c c q u an trao i c h t
cho m t cuc sn g c lp.
V p r e B: xem th th tin t bo B (pre- B- cell receptor).
W e g e n e r s g r a n u lo m a t o s s : bnh to h t W e g e n e r s.
K h n g th ch n g li p rotein ase- ca bch cu c h t tru n g tn h
c h n h th n h trong q u t r n h t o u h t W e g e n e r m t b n h
t m in tron g c cc m ch hoi t trm trng. S h i n d in
ca cc k h n g n gu yn k h n g t bo ch t tru n g tn h (antin eu tro p h il cytop lasm ic a n tig en _ ANCA) l m t d u h iu
ch u n on bnh .

VVeibel- Palade bodies Th VVeibel- Palade l cc ht

tron g t bo ni m cha tc n h n chn lc p. S h o t ho cc t
bo ni m n h cc ch t tru n g gian n h h ista m in v C 5a s dn
ti s di ch y n n h an h ch n g ca tc n h n chn lc p ti b m t
t bo.
W e s t e r n b lo t t in g : k th u t thrn m in dch la i k h n g n gu yn
k h n g th. M t h n hp cc protein s c t ch b i t n h a u
th n g b n g in di trn g el v c ch u y n b n g th m qua
m n g n itrocellu lose; k h n g th c n h du s c s d n g
n h m t m u d kim tra cc protein c h iu .
W h e a l a n d f la r e r e a c t io n : Khi m t lng nh c h t gy d
ng c tim vo da ca m t c th d ng, ng i ta s q u an s t

336
th y p h n n g s n g v N bao gm v n g da ch a dch v
p h n n g vn g nga, v lan rng.
Cc v n g ti t ca m lym pho trong l lch c gi l tu
trn g (w h ite pulp).
W is k o tt - A ld r ic h s y n d r o m e : H i c h n g W is k o t t c m
t bi n h n g th i u st trong b k h un g xng ca t bo do tt
bin tron g p rotein W ASP. B nh n h n b b n h n y r t n h y cni
vi vi k h u n to m .
W u a n d K a b a t p lo t: K h o n g W u v K a b a t (W u and K abat
plot), h a y cc k h on g bin i, c to ra t cc trn h t axt
am in ca cc protein lin quan bng cch ch ra s b in i ca
cc trn h t so vi s cc gc a x t am in. S b in i l s' cc axt
am in k h c n h a u quan s t c d m t v tr c ch ia ra bi lu
s ca a x t am in ph bin nht.
X e n o g e n e ic ; n g v t c to ra t cc loi k h c n h a u c
gi l n g v t d g e n
X e n o g r a t : G h p k h c lo i (xen ograt), gh p c quan t
n h n g loi k h c n h au an g c kh m ph nh l m t g i i php
cho s th i u h t n gh im trng cc c quan c a ngi c n cho cy
ghp. V n ch n h ca vic cy ghp gen khc loi l s xu t
h in cc k h n g th t n h in chng li cc k h n g n g u y n ca b
p h n cy ghp; n h n g c gn g an g c ti n h n h th ay i
p h n n g n y b n g cch to ra nh ng sin h v t c h u y n gen.

Xld (X-linked immunodeficency: Chut mang cc t bin

trong g en btk c s th iu h t trong vic to ra k h n g th, c
b it l tron g n h n g p h n n g s cp. N h n g con c h u t ny c
gi l x ld , th i u h t m in dch lin k t vi nh im s c th X) bnh
ny t ng t nh bnh th iu Y globulin ngi (X- lin k ed agam m aglob u lin em ia).
x > in k e d a g a m m a g lo b u lin e m ia _ XLA : B n h t h i u
g l o b u li n l i n k t n h i m s c t h X (X- lin k ed agam m aglob u lin em ia _ XLA) l m t rl lon di tru yn trong s p h t trin
ca t bo B b km hm giai on t bo tin B (pre- B) v
kh n g t bo trng th n h c n g nh k h n g th n o c to ra.
B n h n y l do th iu s t trong gen m ho cho e n z y m e tyrosin e
k in a se b tk gy ra.

X- linked hyper IgM syndrome :Hi chng qu mc IgM

l i n k t X (X- lin k ed hyper IgM syndrom e) l b n h m c rt t
hoc k h n g c k h n g th Ig G, IgA, IgE c to ra v th m ch

337
c p n g IgM c n g khng nh ng lng IgM tron g h u y t
th a n h li th n g mc cao. B nh ny lin q u an n th iu st
tro n g gen m ho cho cht gn CD40 v C D 154.

X- linked lym phoprolierative syndrome: Hi chng

t n g s i n h l y m p h o l i n k t X (X- lin k ed lym p h op roliferative
sy n d ro m e) l b n h th iu h t m in dch him gp n g u y n n h n
d o (t b in tron g gen c tn l vn g S H 2 cha gen lA (S H 2 D 1 A).
B trai vi s th i u h t ny trong trng hp in h n h s b bi
n h i m EB V tron g thi th u, i khi b u n g th m bch h u yt.

X- linked severe combined imm unodeficiency_

X-

SCID: Thiu h t m i n d c h k t h p t r m t r n g l i n
k t vi X (X- linked severe com bined im m u n od eficien cy_ X-

lin k e d

lin k e d SC ID ) l m t bnh tron g s p h t trin ca t bo T b

n gn li n g a y giai on sm trong tu yn c v k h n g c s sn
xxit t bo T tr n g th n h h ay k h n g th ph thuc t bo T
n o x y ra. B n h ny l do th iu st trong gen m ho ho cho
clhui y.,, m t hp p h n ca m t s' th th i vi m t vi loi
c h t ti t t bo khc n h au (cytok inees).

ZAP- 70: Protein c gi l ZAP- 70 c tm thy cc t

b.o T v l h h n g ca S yk trong cc t bo B. N cha h ai
v n g S H 2 m k h i lin k t vi chui , c ph osp horyl ho s
d n n s h o t ho h ot ng k in a se. C ch t t bo ch yu
ca ZAP- 70 l m t protein th thch nghi kch thc ln gi l
LAT.

339

Ti liu tham kho

1.

2.
3.

4.

5.

V T riu A n, J e a n C laude H om berg (2 0 0 1 ). M in d c h hc,

in l n th h ai, c s a cha, b sung. N h x u t bn Y hc
H N i

N g u y n N gc L anh, Vn n h H oa (ch bin, 2003). M in

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