TRNG I HC NNG LM TP.

H CH MINH KHOA CNTY LP DH08DY

NHM THC HIN 1. Bi Th Cnh 2. Nguyn Hunh Xun An 3. L Th Bch Thy 4. L Th Thu Thy 5. Nguyn Th Ngc Trm 6. Th Tuyt Trinh 7. Nguyn Th Kim L 8. Hunh Tr Ton

Cc khi nim
Min dch (immunity) L kh nng bo v ca c th chng li nhng tc nhn gy bnh xm nhp t bn ngoi: yu t truyn nhim nh vi sinh vt,cn trng,k sinh trng,cc protein l gy c cho c th. Min dch hc (immunus) L mn hc nghin cu v h thng min dch v cc p ng ca h thng ny trc cc tc nhn gy bnh xm nhp vo c th.

H thng min dch L tp hp cc t bo, m v cc phn t tham gia vo qu trnh khng chng nhim trng.

p ng min dch 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.

H THNG MIN DCH

Min dch bm sinh (innate immunity) c vai tr bo v c th ngay lp tc (ngay khi mi sinh ra cng nh ngay khi nhim trng mi xy ra) chng li nhim trng. Min dch thch ng (adaptive immunity) l trng thi min dch xut hin chm hn v tham gia bo v c th chng nhim trng giai on mun hn nhng hiu qu hn.

Cc c ch cn bn ca min dch bm sinh v thch ng

MIN DCH THCH NG

Min dch dch th (Humoral Immunity)

l cch min dch do cc t bo min dch tit khng th vo mu (kt hp vi cc khng nguyn tng ng). Cch min dch c hiu ng nht trong vic chng li s xm nhp ca vi khun,virus n tc ng trung gian qua cc Protein (khng th) hoc globulin min dch (Immunglobulin-Ig) cc khng th ny do t bo lymphocyte B sn sinh do s kch thch ca helper T cell.

MIN DCH THCH NG

Min dch t bo (Cellular
Immunity) l s chng li cc t bo thm nhim virus, k sinh trng, cc m l thng qua cc tc ng trung gian ca cc t bo lymphocyte.

MIN DCH T BO

Cc c quan lympho trung ng

Cc c quan lympho ngoi bin

MIN DCH T BO
Da vo c im,chc nng c th chia thnh 4 nhm: Nhm lymphocyte: lymphocyte T, lymphocyteB, t bo NK(natural killer cells). Nhm thc bo: mono/i thc bo,t bo ui gai,bch cu ht trung tnh,bch cu a axit. Nhm t bo b tr: bch cu a base,dng bo,tiu cu. Nhm t bo khc: t bo ni mch.

Lymphocyte B
Ngun gc : c bt u t gan phi,khong 7-8 tun sau c thai. Sau pht trin ty xng, thnh thc y hoc ti Bursa Fabricius ca gia cm. IgM
IgM CD34 Khng c Ig C C S

T bo gc sinh mu

Tin B (Pro-B cell)

B sm (Early B cell)

B mun (Late B cell)

B chn (Mature B cell)

Qu trnh trng thnh ca B lymphocyte

CC C QUAN TO LYMPHOCYTE B ````````````````````````````````````

C quan trung ng

- Thi k phi: pht trin gan phi.

- Trc v sau : pht trin ty xng.

- Trng thnh: pht trin ty. - loi chim: pht trin ti Bursa Fabricious.

CC C QUAN TO LYMPHOCYTE B
C quan ngoi bin:
- Hch lymphocyte: T bo B sm pht trin trung tm mm,t bo B chn c mt vng Marginal Zone. - Lch: lymphocyte B cha trng thnh c pht trin trung tm mm.B trng thnh c mt mu tun hon. - H thng lymphocyte h tiu ha: amidan, mng Payer ni tp trung t bo B1-B. - Mu tun hon: c mt t bo chn sinh sn t ty xng.

CHC NNG
Sinh ra cc khng th di s kch thch ca Lymphocyte T. mt s i thc bo lm nhim v by v tp trung khng nguyn. Phn ln cc khng nguyn u b cc i thc bo bt v x l.Sau i thc bo c nhim v trnh din cc khng nguyn cho lymphocyte T.

Lymphocyte T
Ngun gc
Lymphocyte T c sinh ra ty xng, di chuyn v tuyn c (thymus) v thnh thc y, sau vo mu, mt t vo hch lm ba.

 S lng t bo lympho T c duy tr n nh nh s cn bng gia cc t bo mi n t tu xng v t bo cht do khng tip xc khng nguyn. Thi gian na i sng ca t bo lympho T nguyn vn vo khong 3-6 thng i vi loi chut v 1 nm i vi loi ngi.

Phn loi t bo T
Da vo chc nng chia thnh 4 loi:
T bo lymphocyte T hiu ng (effector T, k hiu l Te hay cn gi l lymphocyte git-Killer T (Tk )Trc tip tham gia min dch t bo,c kh nng ph hy,phn gii vt l, t bo ung th. T bo lymphocyte T h tr (Helper T cell, k hiu TH ) Hip ng vi bch cu n nhn ln xc tin hot ha t bo lympho B.

 T bo lymphocyte T c ch (Suppesor T, k hiu Ts) C vai tr c ch v hot ha t bo lympho B v cc t bo T khc, tham gia iu ha min dch.
T bo lymphocyte T nh (Memory T, k hiu Tm): Tng sinh v p ng min dch.

Da vo du n protein mng CD tng ng vi chc chia thnh 5 loi: Lympho T h tr ( TH=T helper) -c CD4+ -nhim v hot ha v thc y hot ng ca cc lympho T khc thng qua vic tit ra Interleukin-2. Lympho T gy qu mn mun (TDTH: Delayed Type Hypersensitivity T cell) nhim v tit lymphokin hot ha i thc bo v bch cu khc dn n biu hin qu mn mun.

 Lympho T iu ha ngc (TFR: Feedback

regulator T lymphocyte cn gi l lympho T cm ng c ch) tc dng hot ha lympho T c ch.

Lympho T c ch (Ts=T suppressor)

-c CD8+ -nhim v iu ha p ng min dch, c ch hot ng ca cc loi Lympho bo khc.

Lympho T c (CTL=cytotoxic

lymphocyte=TC) Nhim v tn cng trc tip cc t bo c khng nguyn l trn b mt.

T bo Lympho T vi cc Protein b mt ca n

CHC NNG CC T BO T
Chc nng h tr ca cc t bo CD4: Nhn bit khng nguyn c trnh din bi cc phn t MHC lp II. Thc hin chc nng h tr bng cch tit ra cc lymphokin khi c hot ho (chng hn bi khng nguyn) cc lymphokin s cm ng cc t bo lympho B sn xut ra khng th.

 Chc nng c t bo ca cc t bo CD8: - Ch nhn bit khng nguyn khi kt hp vi cc phn t MHC lp I. - Chu trch nhim v vic ly gii cc t bo c biu l khng nguyn l trn b mt ca chng, c bit nh l khng nguyn virus. Chc nng hot ha i thc bo: - T bo lympho T c kh nng tit ra nhng lymphokin hot ha i thc bo (GM-CSF, IFN, TNF-) - Gip cc i thc bo tr nn hot ng m dit cc vi sinh vt thng xuyn hay nht thi, ngay bn trong cc t bo y

 Chc nng iu ho phn ng vim, to mu: T bo lympho T tit ra cc lymphokin IL-4, IL-5, IL-6 c nhng tc ng khc quan trng trong phn ng vim, to mu. Chc nng iu ha p ng min dch Ca cc t bo lympho T c ch. Khi c suy gim t bo ny th hay xut hin nhng biu hin ri lon min dch nh d ng, t mn

Cc phng php cha bnh trn c s min dch:

Liu php t bo, liu php gen, cc cht kim hm, kch thch min dch v iu ha min dch cha cc bnh nhim trng, bnh t min, bnh suy gim min dch bm sinh hoc mc phi. ng thi liu php min dch c ng dng trong cy ghp thay th cc c quan.

TIM CHNG,VACXIN PHNG V CHA BNH

Tim chng l gy min dch ch ng gip c th c kh nng to ra mt c ch bo v chng li s xm nhp ca mt c th xm lc hoc c t ca n.

Vacxin l cc tc nhn gy bnh dc lm gim bt c tnh hoc lm mt hot ng hoc l cc tiu n v ca cc c t vi khun hoc virus.

CC DNG VACXIN
1.Vacxin vi khun
Cc vi khun c th c git hoc lm mt hoat tnh iu ch tc nhn gy min dch hu ch. a/ Vacxin gim bt c tnh - BCG i vi bnh lao. b/ Vacxinh gy bt hot tnh -Bordetella pertussis i vi ho g. -Salmonella typhi v S.paratyphi i vi bnh st thng hn.

c/ Vacxin cc tiu n v hoc c t: -Neurotoxin ca Clostridium tetani :c iu ch vacxn un vn -c t ca Corynebacterium diphtheriae lm mt hot tnh bng x l ha hc c iu ch vacxin bch hu.

-Polixacarit thnh t bo vi khun Haemophilus influenzae typ c iu ch vacxin vim mng no.

2.CC VACXIN K SINH TRNG

K sinh trng l nhng c th a bo

v k sinh nhiu vt ch trung gian trong vng i ca chng.

N lun thay i c ch tinh vi nhm

trn thot s p ng min dch ca vt ch.

3.CC VACXIN VIRUS

- c iu ch cc dng virus sng 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, bi lit, quai b, bnh si. - Vacxin b git: vacxin bi lit dng tim, vacxin cm, vacxin ch di. - Cc vacxin gm cc tiu n v: vacxin Hepatit B, vacxin cm.

-S DNG CC THUC KiM HM MiN DCH

- S DNG CC XITOKIN V ANTIXITOKIN

- LiU PHP MiN DCH T BO

- LiU PHP GEN CHNG UNG TH

Qu Vit Qut

Bng Ci

Ti - t

Cam - Chanh

C chua C rt

Ng Cc

Tht B - Mng Ty

HOT HA T BO T
Hai tn hiu t cc t bo trnh din khng nguyn - Tn hiu 1: Cht tip nhn ca t bo T nhn din phc hp khng nguynMHC trn t bo trnh din khng nguyn . - Tn hiu 2: L tn hiu ng kch thch qua phn t B7 trn t bo trnh din khng nguyn gn ln phn t CD28 ca t bo T

HOT HA T BO T
T bo T tip xc khng nguyn c kch thch ang giai on GO chuyn sang G1 ca chu k t bo Kch thc gia tng ln khong 8-10m, nhiu bo tng hn, c cc c quan v gia tng lng RNA trong bo tng tr thnh nguyn bo lympho T

HOT HA T BO T
1. Sinh tng hp protein mi
- Ngay sau khi c kch thch, t bo lympho T bt u sao chp cc gen m trc y vn yn lng v tng hp mt lot cc protein mi. - Nhng protein ny gm: + Cc cytokin l cht kch thch s pht trin v bit ho ca chnh t bo lympho v cc t bo hiu qu khc; + Cc th th cytokin lm cho t bo lympho p ng tt hn vi cytokin;

HOT HA T BO T
2. Tng sinh t bo
Cc t bo lympho c hiu vi khng nguyn s chuyn sang thi k phn bo (Go sang G1) to nn s tng sinh mnh m i vi clone t bo c hiu khng nguyn ny.

A: hnh nh KHV quang hc lympho bo mu ngoi vi B hnh nh KHV in t lympho bo nh C hnh nh KHV in t nguyn bo lympho

HOT HA T BO T
3. S bit ho thnh t bo hiu qu
T bo TH: mang trn b mt nhng phn t protein tng tc vi cc ligand trn cc t bo khc (i thc bo trong min dch t bo, t bo B trong min dch dch th), ng thi tit cytokin hot ho cc t bo khc.
T bo TC: mang nhng ht cha cc protein c th git virus v t bo ung th.

HOT HA T BO T
4. S bit ho thnh t bo nh
Bn cnh t bo B, mt s t bo T c bit ho thnh t bo nh. C th tn ti mt cch yn lng trong nhiu nm sau khi khng nguyn c loi b.

HOT HA T BO T
4. S bit ho thnh t bo nh T bo nh c mang trn b mt nhng protein gip phn bit chng vi t bo nguyn vn v t bo hiu qu mi c hot ho.
Intergrin: protein kt dnh CD44: thc y s di chuyn ca t bo nh n ni nhim trng

BIT HA CHN DNG T BO T

Ti tuyn c: 2 qun th chnh
T bo tuyn c vng v
90%

qun th bn trong tuyn c phn ln cha trng thnh c chung mt s du n vi cc tin t bo (CD2) nhng v sau cn xut hin thm mt s khc na.

T bo tuyn c vng li
10%

qun th trng thnh trn mng mt ca chng c nhng du n mi (CD3, CD4 hay CD8) cng nh l receptor T (TCR=T Cell Receptor).

BIT HA CHN DNG T BO T

T bo lympho tip thu mt s hun luyn min dch gm c: kh nng nhn bit khng nguyn kh nng phn bit khng nguyn ca mnh vi khng nguyn l (khng phi ca mnh) S hun luyn qua 2 qu trnh Chn lc dng tnh v chn lc m tnh

BIT HA CHN DNG T BO T

1. S chn lc dng tnh

Lin quan n kh nng nhn bit ra cc phn t MHC trn cc t bo khc thng qua TCR ca t bo tuyn c vng li

Nhng t bo lympho CD4+ Nhng t bo lympho CD8+ c kh nng nhn ra c kh nng nhn bit phn t MHC lp II phn t MHC lp I

Nhng t bo khng nhn bit c

Tip tc qua s chn lc ln 2

cht theo chng trnh (apoptosis)

BIT HA CHN DNG T BO T

2. S chn lc m tnh Lin quan n kh nng phn ng vi khng nguyn bn thn
Cc t bo qua s chn lc dng tnh

c mt i lc qu mnh vi khng nguyn bn thn

kh nng phn ng vi khng nguyn bn thn yu hay khng c

Cht theo chng trnh (Apoptosis)

Di chuyn vo cc trung tm lympho ngoai vi tip tc trng thnh

BIT HA CHN DNG T BO T

Cc du n mng ca t bo lympho T

L cc phn t b mt hnh thnh nhng nhm quyt nh khng nguyn. c coi nh l nhng du n phn bit t bo lympho cc giai on khc nhau Xc nh bng cc ch CD (cluster of differenciation, cm bit ha) theo sau l con s nh trong danh php. Bn cnh nhng du n phn bit, t bo T cn c th th vi khng nguyn gi l TCR (T cell receptor).

BIT HA CHN DNG T BO T T BIT HA CHN DNG T BO

Cc du n mng ca t bo lympho T 1. Phn t CD2

L mt glycoprotein vi duy nht 1 chui 50kD C mt mi t bo lympho T (chn v cha chn) L mt phn t bm dnh vi protein LFA3 c trn cc i thc bo. L mt t hp gm 5 chui t 20-26 kDa: 1, 1, 2, 2 lin kt vi TCR. C mt mi t bo lympho T trng thnh. Vai tr tip xc vi khng nguyn nm trn phn t MHC ca t bo trnh din tng ng v chuyn tn hiu khng nguyn vo trong nguyn sinh cht ca t

2. Phn t CD3

BIT HA CHN DNG T BO T T BIT HA CHN DNG T BO

Cc du n mng ca t bo lympho T

3. Phn t CD4
L mt monomer c 4 khu vc nm bn ngoi t bo c trng ca di nhm qun th t bo lympho T h tr (TH) v c dng nh l ligand vi cc phn t MHC lp II

4. Phn t CD8
Hnh thnh bi 2 chui v ni li vi nhau bng mt dy ni ng ha tr c trng cho di nhm qun th t bo lympho T c (TC) v l ligand ca phn t MHC lp I.

BIT HA CHN DNG T BO T

Cc du n mng ca t bo lympho T

5. Th th ca t bo lympho T vi khng nguyn (T cell receptor-TCR) C 2 loi TCR: TCR1 v TCR2. Khong 95% t bo biu l TCR2, cn 5% l TCR1. 6. Cc th th mng khc ca t bo lympho T + Th th vi mnh Fc ( FcR) ca Ig . + Th th vi IL-2 hay CD25 + Th th vi b th: CD35 hay CR1 v CD21 hay CR2

HOT HA T BO T
T bo T nh c xu hng di chuyn ra ngoi bin n cc hch lympho lu tr nhng t bo lympho c hiu khng nguyn c th c hot ho nhanh tng sinh v bit ho thnh t bo hiu qu khi tip xc tr li vi khng nguyn. Cc t bo nh khc c xu hng tn ti trong nim mc hoc lu thng trong mu th tp trung n bt c v tr nhim trng no trong c th nhanh chng to ra t bo hiu qu gip loi b khng nguyn.

C 3 loi t bo T hiu lc: Loi 1. Nhng khng nguyn ca cc tc nhn gy bnh pht trin trong bo tng (virut), cc protein ni bo v protein c hiu u (protein ni sinh) s c vn chuyn ln b mt t bo bi phn t MHC lp I v trnh din cho t bo TCD8 gy c n trc tip dit t bo nhim.

P NG MIN DCH CA T BO T

P NG MIN DCH CA T BO T Nhng khng nguyn ca nhng vi sinh vt gy

bnh pht trin trong nhng ti ni bo v c vi khun tip nhn ngoi bo, c t (protein ngoi sinh) s c vn chuyn ln b mt t bo bi phn t MHC lp II v trnh din cho t bo lympho TCD4.

Loi 2: t bo lympho T gy vim (TH1): hot ha

i thc bo nhim i thc bo c th tiu dit cc tc nhn gy bnh ni bo.
bo lympho B sn xut khng th chng li

Loi 3: t bo lympho T h tr (TH2): kch thch t

P NG MIN DCH CA T BO T

Khi ng p ng min dch vi t bo T CD4

Min dch trung gian t bo

T bo lympho T CD4 gy vim (TH1) nhn din phc hp KN-MHC lp II trn i thc bo nhim hot ha i thc bo nhim i thc bo hot ha mi tiu dit tc nhn gy bnh. V d c ch khng vi vi khun lao, vi khun Hansen, Pneumocytis carinii...

T bo lympho T CD4 h tr (TH2) nhn din phc hp KN-MHC lp II trn t bo trnh din khng nguyn tit ra cytokin (IL2, IL6, INFg) kch thch tin t bo T gy c thnh t bo T c hiu lc gy c (Tc) ly gii t bo ch. V d c ch khng vi virus cm , c t ...

P NG MIN DCH CA T BO T

Khi ng p ng min dch vi t bo T CD4

Min dch dch th

T bo lympho T CD4 h tr nhn din phc hp KN MHC lp II trn t bo lympho B c hiu hot ha t bo lympho B cho vic sn xut khng th chng tc nhn gy bnh. Bng cch tit cytokin, t bo lympho T CD4 tp trung cc t bo hiu ng khng c hiu v kch thch chc nng hot ng ca chng bin cc t bo ny tr thnh cc yu t tham gia vo p ng min dch c hiu :
+ TNF- a v LT : hot ha bch cu a nhn trung tnh v t bo ni mc mch mu. + IL5 : hot ha bch cu i toan. + IFN-g :hot ha bch cu n nhn. + IL2 : hot ha t bo NK, t bo T v c t bo B

P NG MIN DCH CA T BO T

Nhn bit khng nguyn v hot ha

P NG MIN DCH CA T BO T

1. S bit ha t tin Tc thnh t bo Tc c th gy c trc tip . Cn 2 tn hiu

S C T BO TRUNG GIAN QUA T BO T

+ Tn hiu 1: Cht tip nhn t bo T nhn din phc hp KN-MHC lp I trn t bo trnh din khng nguyn hoc t bo ch . + Tn hiu 2: Cytokin do t bo T CD4 tit ra (IL-6, IL-2, IFN-g) khi n nhn din chnh khng nguyn y trn t bo trnh din khng nguyn

P NG MIN DCH CA T BO T

2. Chc nng chnh ca t bo Tc Ly gii t bo ch t bo Tc c kh nng git cht cc vi sinh vt pht trin trong bo tng (vi rt v mt s vi khun). ng thi cng c kh nng git cht cc t bo ung th v cc t bo ghp. Ch git mt cch c chn la nhng t bo ch c bc l khng nguyn c hiu. T bo TCD8 TC cng sn xut IFN-g v c TNF-a km hm s nhn ln ca vi rt, lm tng s bc cc phn t MHC lp I v hot ha i thc bo.

S C T BO TRUNG GIAN QUA T BO T

P NG MIN DCH CA T BO T

3. C ch ly gii ca t bo Tc. Trc ht t bo Tc gn ln t bo ch thng qua cht tip nhn c hiu KNMHC lp I.

S C T BO TRUNG GIAN QUA T BO T

P NG MIN DCH CA T BO T

3. C ch ly gii ca t bo Tc. Cch 1: gy hiu lc c trc tip bng cch gii phng 2 loi cytotoxin l fragmentine v perforin.

S C T BO TRUNG GIAN QUA T BO T

Perforin to nhng l thng qua mng t bo ch fragmentine c th i vo trong t bo v tiu dit t bo ch git cht t bo

Cch 2: hot ha enzym phn ct phn t DNA ca t bo ch DNA b phn ct t bo ch t hy qu trnh Apoptosis.

Vai tr ca h thng min dch

khng vi nhim trng H thng min dch nhn din v p ng chng li cc mnh ghp v cc protein l c a vo c th Chng ung th Cc khng th l cc cht th c tnh c hiu cao dng xc nh cc loi phn t khc nhau

nh hng

Ngi b suy gim min dch d b cc bnh nhim trng (v d bnh nhn AIDS). Vaccine c tc dng tng cng kh nng min dch v chng nhim trng. Cc p ng min dch l nhng ro cn quan trng i vi ghp t bo, m, v c quan cng nh tr liu gene Tim nng ng dng min dch tr liu cho ung th. Cc phng php min dch c dng rng ri trong xt nghim y hc cng nh cc ngnh khoa hc khc.

c im ca cc p ng min dch thch ng

c im Tnh c hiu Tr nh Tnh chuyn bit Tnh khng phn ng vi cc khng nguyn ca c th

c im ca cc p ng min dch thch ng

Tm quan trng i vi min dch chng vi sinh vt Kh nng nhn din v p ng vi nhiu loi vi sinh vt khc nhau. Cc p ng mnh hn i vi cc trng hp ti pht hoc nhim trng ko di. Cc p ng chng li cc vi sinh vt khc nhau c ti u ho chng li cc vi sinh vt . Ngn cn cc p ng min dch gy tn thng cho cc t bo v m ca c th.

Tnh c hiu v tr nh min dch ca min dch thch ng

Cc pha ca p ng min dch thch ng

Cc pha ca p ng min dch

Cc p ng min dch bao gm chui cc pha k tip nhau t nhn din khng nguyn, hot ho cc t bo lympho, loi b khng nguyn, thoi tro, v tr nh min dch. Mi pha tng ng vi nhng phn ng c trng ca cc t bo lympho v cc thnh phn khc ca h thng min dch. Trong pha nhn din khng nguyn, cc t bo lympho c hiu khng nguyn nhng cha tng tip xc vi khng nguyn s khu tr v nhn din cc khng nguyn ca vi sinh vt.