H thng b th

B Th (complement)

B th l mt nhm protein trong mu.

Kt hp ca b th v khng th c vai tr rt quan trng trong

vic loi tr mm bnh.

B th c kch hot ngay khi mm bnh va xm nhp vo

c th.

Khng c tnh c hiu nn b th c xem nh l thnh phn

thuc h thng min dch bm sinh.

Khng th cng c kh nng hot ha mt vi protein ca b

th. Qu trnh ny cng l mt phn trong min dch dch th.
 Cc thnh phn ca h thng b th
Cc protein ca b th c sinh ra cc t bo gan v
i thc bo.

Chng tn ti trong h thng tun hon nh nhng phn

t khng hot ng.

Mt vi protein ca b th th dng tin enzyme (Pro

enzyme).

Khi c hot ha, cc phn t ny tr thnh cc enzyme

protease. Cc enzyme ny s ct cu ni peptide ca
nhng protein b th khc hot ha nhng protein ny.

Mt protease c th hot ha c rt nhiu phn t

protein. Qu trnh hot ha ny s c khuch i mt
cch nhanh chng to nn hng triu phn t hot
ng.
Nhng protein thnh phn ca b th nh s t C1 n C9 theo
trnh t m chng tham gia phn ng (tr C4 l k hiu theo trnh
t pht hin b th).
Trong sut qu trnh hot ha, mt vi thnh phn cu trc b th
c chia lm 2 phn:
+ Phn ln hn ca phn t c gi l b (binding) thng gn
kt vi mm bnh.
+ Phn nh hn gi l a (activated) c th phn tn i (tr C2:
phn ln l C2a v phn nh l C2b).
+ Cc yu t: B, H, I, P (properdin), MBL, MASP (Mannan-
binding lectin serine peptidase) 1, MASP 2 (MBL
Assosiated Serine Protease)
+Yu t iu ha: C1 Inhibitor (C1 INH = Serpin), C4
Binding protein (C4PB), Yu t tng cng thoi bin
(Decay Accellerating factor), Th th 1 (CR1); Protein S (
vitronectin).
 Vai tr

Hot tnh lm tan t bo: phc hp tn cng mng MAC (membrane attack
complex) chc thng mng t bo, to cc l trn mng lm tan t bo, gy
cht t bo

Tham gia c ch opsonin ha: lm cho vic thc bo d dng hn

Tng cng p ng vim:cc c t phn v c tc dng co bp c trn,

tng tnh thm thnh mch gip cho s thot mch, kch thch t bo Mast
gii phng cc cht trung gian gy vim nh histamin

Tnh ha hng ng: c kh nng thu ht cc t bo thc bo

 Cc c ch hot ng
bo v c th chng li s xm nhp ca mm bnh:
Cc protein b th thnh phn phi c hot ha:
Cc thnh phn ny c kch hot thng qua 3 con ng khc nhau:

+ Con ng c in
+ Con ng nhnh
+ Con ng lectin

Cc con ng hot ha c khi ng bng cc protein b th khc nhau nhng li

sn sinh ra cng mt b cc phn t hot ng.

Sau khi hot ha, h thng b th c 3 cch bo v c th

chng li s xm nhim ca vt ngoi lai:
+Sn sinh ra mt lng ln protein b th c hot ha lin kt vi mm
bnh, opsonin ha chng to iu kin cho cc i thc bo m c th th vi b
th n cc mm bnh
+ Nhng mnh nh ca cc protein b th lm tng cng p ng vim. Ngai ra,
mt trong nhng mnh c hot tnh ha hng ng nhm thu ht bch cu
+Th ba, nhng thnh phn cu trc b th giai on cui hy hoi mt s vi khun
bng cch to ra nhng l trn mng ca n.
Cc con ng hot ha
Con ng c in
y l con ng hot ha c vai tr quan trong trong min dch bm sinh v
min dch c hiu.

Con ng ny c hot ha thng qua:

Mt p ng min dch nh s gn kt C1q (protein u tin ca dy chuyn hot ha

b th) vo phc hp KN-KT (c th gi l con ng hot ha ph thuc vo khng
th)

C th c khi ng bi s gn kt trc tip C1q ln b mt vt ngoi lai

Cc protein thnh phn

Cc protein tham gia vo con ng c in gm: C1qrs, C2, C3, C4
C1q cn phi gn vi t nht l hai Fc vo cc u hnh cu to
ra lin kt bn vng
Qu trnh hot ha

S hot ha C1 do C1 gn vo khng th thng qua C1q dn n s hot ha C1r,

v C1s:

Thnh phc hp C1qrs hot ha:

Ct C4 thnh 2 phn l C4a v C4b:
C4b gn kt vo mng v mnh C4a c phng thch ra ngoi dch
Ct C2 thnh C2a v C2b (C2b l mnh ln cn C2a l mnh nh):
C2b gn vo mng, kt ni vi C4b to thnh phc hp C4bC2b (C3
convertase)
C3 convertase s ct C3 thnh C3a v C3b
C3b gn v mng bng cch lin kt vi C4b v C2b, cn C3a c gii phng ra
th dch.

Thnh phc hp C4bC2bC3b, hay chnh l C5 convertase.

S to thnh C5 convertase l kt thc con ng hot ha c in.

Con ng Mannose-binding lectin (MBL)
Cu trc

Cu trc tng t C1qrs vi mt phn t MBL c 6 tiu n v ging C1q, mt

phn t MASP-1 v MASP-2 gn vo MBL nh C1r v C1s

Qu trnh hot ha

Con ng lectin rt ging vi con ng c in.

Hot ha bi s kt ni ca mannose-binding lectin (MBL) vo b mt vi khun ti
polysaccharide cha mannose.
S gn kt ca MBL vo mm bnh dn n s kt hp ca 2 protease serine l
MASP-1 v MASP-2.

MASP-1 v MASP-2 ging vi C1r v C1s, trong khi th MBL ging vi C1q.
Phc hp ca 3 phn t MBL, MASP-1, MASP-2 dn n s hot ha ca
MASPs v tip theo l s phn tch C4 thnh C4a v C4b.

Mnh C4b gn vo mng t bo mm bnh v C4a c phng thch ra th dch.

MASPs hot ha cng ct C2 thnh C2a v C2b, C2a gn vo mng t bo vi
khun cn C2b c gii phng ra th dch.
S hnh thnh phc hp C4bC2a, hay chnh l C3 convertase.

C3 convertase ct C3 thnh C3a v C3b, C3b gn vo mng vi khun bng vic kt

hp vi C4b v C2a.

C4bC2aC3b, hay chnh l C5 convertase.

S sn sinh ra C5 convertase l bc cui cng ca con ng lectin

Con ng nhnh
Con ng nhnh (alternative pathway).
Con ng nhnh rt quan trng: khng cn thit phi c phn ng khng nguyn-
khng th khi ng h thng b th, m ch cn cc tc nhn b mt t nhin
nh: v t bo nm men, polysaccarrit v vi khun, nc rn h mang, hng cu
th...

Khi mm bnh ln u tin xm nhp vo c th, trong iu kin khng th c

hiu chng li mm bnh ny vn cha c to ra, th con ng nhnh vn
c th c khi ng chng li khng nguyn l ny.

Qu trnh hot ha
C3 c rt nhiu trong huyt tng.
Mt s C3 c tri qua qu trnh thy phn t ng v chuyn thnh C3(H2O).
Yu t B mi c th bm vo C3(H2O).

S bm ny cho php yu t D ct yu t B thnh 2 mnh Ba (mnh nh) v Bb

(mnh ln) to thnh phc hp C3(H2O)Bb.
C3(H20)Bb l mt convertase C3, tuy ch hnh thnh mt lng nh nhng c th phn
ct rt nhiu phn t C3 thnh C3a v C3b.

Ch rng rt nhiu C3b b bt hot bi hin tng hy phn, ch nhng C3b no bm

c ln b mt t bo ch hoc t bo vt ngai lai mi c kh nng hat ng.

Nhng C3b c kh nng hot ng, va c to ra t phc hp C3b(H2O)Bb, s li

lin kt vi yu t B.

Khi yu t B l ra v tr chu tc dng ca yu t D. V di tc dng ca yu t D,

th yu t B nm trong phc hp C3bBb b phn tch ra lm 2 mnh Ba v Bb c gn
trong phc hp C3bBb. y chnh l dng phc hp ch lc phn ct C3 thnh C3a
v C3b.V c th tip tc to ra cc convertase C3.

Tuy nhin cn nhn mnh, khi C3bBb bm ln b mt t bo ch th cc protein iu

ha b th (CR1, H, MCP, DAF) s cnh tranh gn kt vi C3b v y Bb ra to
phc hp mi. V th ct t con ng to convertase C3. Trong khi C3bBb bm
ln b mt vt ngai lai vn c th phn ct C3 thnh C3a v C3b c l do:
Vt ngai lai thiu cc protein iu ha
C thm yu t P c hp ph vo nhm C3bBb lm cho n nh phc hp
C3bBb
Bc tip theo trong chui phn ng dy chuyn hat ha b th l to ra
convertase C5.
Trong con ng c in v MB-lectin th convertase C5 c hnh thnh bng
cch: Gn C3b vo convertase C3 (C4bC2a) thnh C4bC2aC3b.

c hnh thnh t s bm ca C3b vo C3bBb thnh C3bBbC3b.

C CH BO V C TH CA H THNG B TH
Giai an dn n tn thng mng :

C 3 con ng hat ha h thng b th cui cng u dng li mt mc

chung, l to ra convertase C5 (C4bC2aC3b/C3bBbC3b)-c vai tr nh mt cht
xc tc.

T y m ra mt giai an quyt nh chng li cc vt l xm nhp.

hnh thnh phc hp MAC,bc u tin l phn ct C5 thnh C5a v C5b
bng cch :

C5 s lin kt vi C3b ca convertase C5 -c hnh thnh t giai an trn

Sau C2a v Bb (thnh phn ca convertase C5) s ct C5 thnh 2 mnh C5a
(nh) v C5b (ln)
C5b c 2 v tr gn : mt v tr gn vo t bo ch ngay sau khi C5b c to
thnh v mt v tr gn vi C6 to phc hp C5bC6.

Phc hp ny li gn vi C7 to thnh C5bC6C7.

Tip theo l C8, n l mt phc hp gm 2 protein, C8 v C8-:

C8 va lin kt vi mng t bo mm bnh, va lin kt vi C5b trong phc

hp C5bC6C7. Nh vy m phn k nc ca C8- c th xuyn qua lp
mng lipid kp.

Cui cng l s trng hp ca 10-16 phn t C9 vo cu trc l trn mng.

 S tng ng gia ba con ng

Con ng c in Con ng Lectin Con ng nhnh

S tng cng p ng vim
Hat ng phn ct C4,C3 hay C5 nh cc phc hp xc tc lun to ra 2 mnh : 1
nh v 1 ln. Mnh ln c gi li trong cc phc hp tip tc tham gia to
MAC. Cn cc mnh nh c gii phng ra ngai th dch thc hin chc nng
ring ca n.
Cc mnh nh c cp chnh l cc C3a,C4a v C5a, hot ng trn cc th
th ring bit gy nn cc p ng vim cc b. (C5a l c hat tnh cao nht)

C C3a,C4a,C5a gy ra cc triu chng nh co tht c trn, tng tnh thm thnh

mch, tng cng s lin kt ca bch cu ln thnh mch ti ni b vim. Dn
n :

R r cc cht dch t mch mu

S that khi mch mu cc phn t min dch v b th

Tng s di chuyn ca cc i thc bo, lympho n vng m c s xm nhim

ca mm bnh. ng thi hat ng ca cc t bo ny cng c tng cng.
c bit C5a cn :

Hat ha t bo Mast gii phng ra cc cht ha hc trung gian nh histamine v

TNF- gy ra cc p ng khi vim.
C5a c tnh ha hng ng hp dn cc bch cu trung tnh, i thc bo n
thc bo cc vt ngai lai

=>Kt thc giai an ny, phc hp tn cng mng li v s cc l thng trn

lp mng lipid kp:

Cc cht ha tan v nc vn chuyn t do qua mng, dn n s mt cn bng

trong t bo vt l.

Mt s enzyme nh lysozym c th xm nhp vo lm tan t bo.

Cui cng s tiu dit vt ngai lai.

S opsonin ha
Mt vai tr cng rt quan trng ca b th l tham gia vo s opsonin ha.
Mt mm bnh l khi xm nhp vo c th, s xy ra qu trnh tip xc gia khng
nguyn v b th.

Khi h thng b th c hat ha chng li mm bnh, sn sinh ra C3b v C5a.

C5a c tnh ha hng ng, v th c th xem nh mt tc nhn hp dn, mi gi cc

bch cu trung tnh, i thc bo n vy bt vt l xm nhp c th

Yu t gip cc bch cu ny d dng nhn din, lc ny chnh l vai tr ca C3b

trong c ch opsonin :
Nu khng nguyn l xm nhp c th ln u tin th khng nguyn s c bao
ph bi yu t b th C3b, y l iu quan trng gip cho cc t bo thc bo, c bit
l cc i thc bo nhn din v n khng nguyn l .V trn cc t bo y c cc
th th cho yu t C3b, nn to c iu kin thun li cho s thc bo.

Nu khng nguyn l tng xm nhp vo c th, th c th s c khng th chng li

bnh, lc ny khng nguyn l s c c khng th v b th gn ln b mt. Mt khc
trn b mt t bo thc bo c th th cho khng th, v cng c c th th ca b th
C3b, v vy xut hin c 2 tn hiu gip t bo thc bo nhn din. iu ny to s d
dng hn cho vic gn khng nguyn vo t bo thc bo.
Chnh s gn kt ny thc y cho tin trnh ph hy khng nguyn.
S IU HA HOT NG B TH
Cc yu t iu ha:

Cc yu t iu ha b th
Yu t iu ha V tr Chc nng
C1 INH Huyt thanh Ct t lin kt ca C1 hat ha
Ct t lin kt C3 convertase con ng c in
C4 binding protein (C4BP) Huyt thanh
Cofactor cho yu t I
Properdin Huyt thanh n nh C3bBb3b
Ct t lin kt ca C3 convertase trong con ng nhnh
Factor H Huyt thanh
Cofactor cho yu t I
Factor I Huyt thanh Lm thai bin C4b v C3b
Serum proteases Huyt thanh Bt hat c t phn v (C3a, C4a)
S protein(vitronectin) Huyt thanh Ngn cn s gn kt ln mng ca C567
Ct t lin kt ca C3 convertase
CR1 Mng
Cofactor cho yu t I
Ct t C3, C5 convertase
Decay Accelerating Factor (DAF, CD55) Mng
Cofactor cho yu t I
Membrane Cofactor Protein (MCP, CD46) Mng Cofactor cho yu t I
Homologous RestrictionFactor (HRF, C8BP, MIP) Mng c ch s hnh thnh MAC
MIRL (protectin, CD59) Mng c ch s hnh thnh MAC
C1-INH: gn vo phc hp C1rC1s hat ng v lm cho phc hp ny tch ra khi
C1q (phn ang gn vo b mt t bo).

C1-INH hn ch s phn ct C2 v C4 bi C1s.

C1-INH l yu t iu ha chnh ca con ng c in v C1qrs l l bc u tin

ca tin trnh: ct t C1 dn n ngng s hot ha tt c cc thnh phn khc.

DAF (decay accelerating factor) l yu t iu ha cn thit cho con ng nhnh v

n ngn cn s hot ha t ng C3b bng cch ngn cn s gn kt ca yu t B
vo C3b.

C ch hot ng ca DAF: Khi C3b gn kt vo th th CR1 trn mng t bo vt

ch, n ng thi c gn kt vo DAF trn mng v lm hot ha DAF. DAF c
hot ha s c chc nng ngn cn s kt hp gia C3b v yu t B.

Thm vo , nu C3b gn kt vi Bb trc khi n gn kt vi CR1 ca mng t

bo vt ch th DAF s c tc dng tch Bb ra khi C3b, dn n ph v phc hp
C3bBb.

CR1 v MCP: l 2 lai protein mng t bo vt ch m gn kt C3b v C4b ng thi

l cofactor cho yu t I. Thnh t bo vi khun thiu nhng protein bo v ny v
khng th tng cng s ph hy C3b v C4b. Thay vo nhng protein ny hat
ng nh nhng v tr gn kt cho yu t B v C2, tng cng s hat ha b th
Factor I: khi C3b gn kt vo CR1 trn mng t bo, n tr nn nhy cm v d dng b
yu t I ct thnh iC3b (dng bt hat ca C3b).
C4b cng b bt hat bng cch b yu t I ct thnh C4c v C4d

Yu t H: l 1 yu t iu ha quan trng ti mng t bo. Yu t H v yu t P cnh

tranh vi nhau gn kt vi C3b m gn vo mng t bo.
Nu yu t P thng, trong trng hp trn mng t bo vi khun th nhiu C3b, Bb C3
convertasa v s hat ha b th c tng cng.

Nu yu t H thng nh trng hp trn t bo vp ch, sau C3b gn kt trn mng

t bo s b ct bi yu t I tr thnh iC3b v s hat ha b th b c ch.

Protein S: khi mt s phc hp C5bC6C7 c hnh thnh c th khng lin kt vi

mng t bo mm bnh m li i vo th dch, t chng c th gn kt vi cc t bo
lnh ca vt ch v lm tan chng.
S hy hoi ci t bo vt ch ny c ngn chn bi protein S. Protein S gn kt vo
phc hp C5bC6C7 t ngn n gn vo cc t bo khc