T細(xì)胞激活課件

T細(xì)胞激活TCellActivation-T細(xì)胞激活和增殖涉及的分子與信號(hào)信號(hào)轉(zhuǎn)導(dǎo)過程T細(xì)胞功能性亞群的分化記憶T細(xì)胞超抗原-T細(xì)胞激活和增殖涉及的分子與信號(hào)第一信號(hào)（抗原信號(hào)）第二信號(hào)（協(xié)同刺激信號(hào)）CK信號(hào)TCR-肽-MHC三元體+CD4/CD8CD3胞內(nèi)段ITAM轉(zhuǎn)導(dǎo)信號(hào)CD28-B7IL-2與IL-2R（使T增殖）IL-12、IL-4、IL-23使T分化--T細(xì)胞抗原識(shí)別信號(hào)的轉(zhuǎn)導(dǎo)

pathwayApathwayB

pathway

CPKCcalcineurinMAPkinasePIP2

DAG+IP3Ras-GDPRas-GTPCa2+RafPLC-SosNF-ATOCTNF-BAP-1NF-ATOCTPKCGrb-2I-BNF-BNF-BNF-AT

NF-AT-pc-Junc-FosAKTB7CD28

PI3-KLATSLP-76ZAP-70Peptide-MHCTCRLckFynCD45CD4PTPdomainsY505pITAMITAMYpYpNUCLEUSCELLMEMBRANEIL-2geneYpYpYpGSK3GadsNCK細(xì)胞骨架重排免疫突觸PIPIP3-TCRCD3ITAM受體交聯(lián)成簇偶聯(lián)PTK活化（Lck、Fyn）ITAM磷酸化（活化）招募胞漿PTK（ZAP-70）PTK磷酸化（活化）激活銜接蛋白-PLC-PIP2DAG+IP3GEF（Sos）激活PKC活化鈣調(diào)磷酸酶活化MAP激酶級(jí)聯(lián)反應(yīng)活化轉(zhuǎn)錄因子（NF-B、NFAT、AP-1）與特異性基因的啟動(dòng)子結(jié)合，啟動(dòng)基因轉(zhuǎn)錄轉(zhuǎn)位-CD3和CD4的胞內(nèi)段連接有PTKCD3的胞內(nèi)段具有ITAM結(jié)構(gòu)-

Src

family:Lck,Fyn,Lyn,BlkTyrosinekinase

Sykfamily:ZAP-70,Syk

Jakfamily:Jak1,Jak2,Jak3ProteinkinaseCskfamily:Csk

ProteinkinaseC(PKC)Serine/threonineMAPkinase(MAP:mitogen-activationkinaseprotein)

PI3kinase(PI:phosphatylinositide)

TyrosinephosphataseCD45

Proteinphosphatase

Serine/threonineCalcineurin鈣調(diào)磷酸酶phosphatase

ProteinkinasesandproteinphosphatasesinT/Bactivation蛋白激酶蛋白磷酸酶蛋白酪氨酸激酶PTK蛋白酪氨酸磷酸酶PTP蛋白激酶Ｃ蛋白絲/蘇氨酸激酶P-ITAM基序(免疫受體酪氨酸激活基序)immunoreceptortyrosinebasedactivationmotif以YxxL/V4個(gè)氨基酸殘基為基本結(jié)構(gòu)的序列存在于CD3、IgIg、FcRIII(CD16)、FcRI等活化性受體的胞內(nèi)段（T、B、NK、肥大細(xì)胞）其酪氨酸被磷酸化后，可招募含有SH2結(jié)構(gòu)域的一些游離胞漿分子，參與信號(hào)轉(zhuǎn)導(dǎo)的級(jí)聯(lián)反應(yīng)為T、B細(xì)胞轉(zhuǎn)導(dǎo)抗原刺激信號(hào)所必需---銜接蛋白：LAT（、SLP-76）招募Grb-2、Gads和PLC-磷脂酰肌醇途徑Grb-2

招募GEF（Sos）MAP激酶途徑Gads

招募NCK免疫突觸形成--鳥苷酸置換因子：guaninenucleotideexchangefactor，GEF小G蛋白：smallGTP-bindingprotein-Erk-andJnk-pathwaysinMAPkinase-relatedsignalingcascade?PakRafMekkMekLnkkErkJnkFosJunAP-1RasRac,cdc42TactivationBactivation/StressGTPproteinMAPKKKKMAPKKKMAPKKMAPKTranscriptionfactorp38-協(xié)同刺激信號(hào)的轉(zhuǎn)導(dǎo)

pathwayApathwayB

pathway

CPKCcalcineurinMAPkinasePIP2

DAG+IP3Ras-GDPRas-GTPCa2+RafPLC-SosNF-ATOCTNF-BAP-1NF-ATOCTPKCGrb-2I-BNF-BNF-BNF-AT

NF-AT-pc-Junc-FosAKTB7CD28

PI3-KLATSLP-76ZAP-70Peptide-MHCTCRLckFynCD45CD4PTPdomainsY505pITAMITAMYpYpNUCLEUSCELLMEMBRANEIL-2geneYpYpYpGSK3GadsNCK細(xì)胞骨架重排免疫突觸PIPIP3-細(xì)胞因子受體啟動(dòng)的信號(hào)轉(zhuǎn)導(dǎo)---T細(xì)胞功能性亞群的分化CD4Th1

CD4Th2

CD4Th17CD8CTLTCR配體pMHCII類

pMHCII類

pMHCII類

pMHCI類誘導(dǎo)因子IL-12、IFN-IL-4IL-23IL-2轉(zhuǎn)錄因子STAT4

STAT6/GATA3

STAT3/RORt

STAT1/T-bet

表面效應(yīng)分子CD40L、FasL

CD40LFasL分泌效應(yīng)分子IFN-、TNF-、

IL-4、5、10、13

IL-17、IL-17F

穿孔素、

IL-2、IL-3、

GM-CSF

顆粒酶、IFN-、

TNF-、GM-CSFTNF-、TNF-主要靶目標(biāo)吞噬病原體的M

Ag特異性B

炎癥細(xì)胞感染病毒的靶細(xì)胞應(yīng)答類型細(xì)胞免疫

體液免疫

炎癥反應(yīng)特異殺傷-naiveCD4T

Th0Th2Th1Stat1T-betGata

3IL-12IL-4IL-12R1/2IFNR1/IFNR2cIL-4R

IFN-

TNFIL-2IL-4IL-5IL-13CCR3,4,8

CxCR7CxCR3CCR5Stat

4Stat

6AgMHCcostimulationRORtIL-17IL-17F

Stat3IL-23Il-23RIL-12R1

Th17IFN-

CD4T細(xì)胞功能性亞群的分化-CD8CTL的分化與作用--記憶性T細(xì)胞效應(yīng)性記憶T細(xì)胞（TEM）中樞性記憶T細(xì)胞（TCM）保護(hù)性記憶