T淋巴细胞介导的细胞免疫应答.ppt

,第十二章T淋巴细胞介导的细胞免疫应答,免疫学教研yx939,目标,免疫应答（immuneresponse）,概念免疫细胞识别抗原后活化、增殖、分化为效应细胞，并通过其所分泌的抗体或细胞因子表现出一定生物学效应的过程。,适应性免疫应答的基本原理,类型,1,2,3,4,5,适应性免疫应答的基本过程,局部组织,引流淋巴管,树突细胞,异物抗原,APC启动适应性免疫应答,外来抗原的捕获与递呈,TC,TCR,MHC-I,Th1,TCR,MHC-II,Cellularimmunity,CTL:CytotoxicTLymphocyte,(1)T细胞与APC的黏附,(2)TCR扫描APC表面,(3)T细胞通过TCR对抗原肽进行识别,abTCR,abTCR,CD8,抗原肽,HLA-I,抗原肽,HLA-II,TCRCo-receptor-CD4和CD8,TCR立体结构-,DiversityandSpecificity,TCR识别MHC/抗原肽的分子解剖,MHC-a螺旋,抗原肽,CDR1,CDR2,CDR3,CDR3,CDR2,CDR1,TCR-b链,TCR-a链,MHC-a螺旋,403020100,102030405060708090100110,TCRVa区氨基酸序列,氨基酸残基的变异百分率,TCR的多样性,CDR1,CDR2,CDR3,ab-TCR的多样性与抗原特异性,-S-S-,Va,Ca,Vb,Cb,g,e,d,-S-S-,TCR-ab,CD3复合体,z,h,z,z,-S-S-,TCR-CD3复合分子,e,胞膜,胞浆,ITAM,糖基,TCR-CD3复合分子,ITAM:Immunoreceptortyrosine-basedactivationmotifs,APC,Th细胞活性封闭,Th细胞活化的双信号模型,IL-2R,APC,Th,信号1,信号2,炎症LPS细菌,化学趋化因子补体TNF-aIL-1IL-6,IL-2,Th,信号1,Th细胞活化、增殖,(4)T细胞活化的“双信号模型”,A活化,*,免疫突触immunologicalsynapse,fyn,PLC,Ca+,ZAP-70,激酶链的信号整合,转录因子被活化,早期基因,IL-2基因,IL-2Ra基因,T细胞活化的信号转导,CD4,TCR,LCK,PI-3k,Activation,Anergy,抗原特异性淋巴细胞的克隆扩增与选择,03581520304050100200300400,1010,7,6,1010,5,4,3,1010,2,40,CTL,病毒,CTL(%),60,80,20,IL-2andIL-2RforTcells,T,Th2,Th?,Tc1,Tc2,Treg,Th0,CD4+,Tc,CD8+,Treg,CD4+25+,EffectorTCells(效应T细胞),辅助性T细胞：,Tc细胞：直接杀伤靶细胞,Th1,Th2,细胞免疫,体液免疫,分泌细胞因子,Th,CD4+,Tc,CD8+,CD4+,(1)辅助性T细胞：,活化,分泌细胞因子,a.效应性Th1细胞,IL-2：促进T细胞增殖IFN-：活化M增强其表达MHC-II分子的表达TNF-：使血管内皮细胞表达粘附因子，分泌趋化因子,细胞免疫，炎症反应（胞内感染），迟发性变态反应（DHT）,活化,b.效应性Th2细胞,抗体生成类别转换,B细胞增殖、抗体生成,2.杀伤性T细胞CTL,CTL,CTL细胞活化的双信号模型,活性封闭,APC1,CTL,IL-2,活化扩增,Th,CTL,APC2,*,图CTL介导的靶细胞杀伤过程,靶细胞,颗粒,CTL,CD8TCR,MHCI-肽,CTL细胞,器重排,CTL颗粒,外吐,膜损伤,偶合物,形成,CTL再循环,效应阶段,Flashlymphocytedevelopmentinductionofapoptosis,FADD:FAS相关的含死亡区域的蛋白,Caspase-8:胱冬肽酶8,CAD:CaspaseactivatedDNase,Phagocyteswithingestedmicrobes;microbialantigensinvesicles,Infectedcellwithmicrobesincytoplasm,CD4+effectorTcells(TH1cells),CD8+Tcells(CTL),CD8+Tcells(CTL),Macrophageactivation:killingofingestedmacirobes,Inflammation,Killingofinfectedcells,TypesofTcell-mediatedimmunereactions,CD8+Tcells(CTL),CD4+effectorTcells(TH1cells),CD4+Tcells,CD8+Tcells,Antigenrecognitioninlymphoidorgens,Tcellexpansionanddifferentiation,DifferentiatedeffectorTcellsentercirculation,EffectorTcellencounterantigensinperipheraltissues,MigrationofeffectorTcellsandotherleukocytestositeofantigen,DifferentiatedeffectorTcellsentercirculation,EffectorTcellencounterantigensinperipheraltissues,EffectorfunctionsofTcells,Macrophageactivation:killingofphagocytosedmicrobes,CTLkillingoftargetcell,ActivationofeffectorTcells,Theinductionandeffectorphasesofcell-mediatedimmunity,naiveCD4+Tcells,APC,Microbes,Proliferationanddifferentiation,IFN-,IFN-,LT,TNF,Bcell,TH1cells,Fcreceptor,Macrophageactivation(enhancedmicrobialkilling),Complement-bindingandopsonizingantibodies,Opsonizationandphagocytosis,Neutrophilactivation(enhancedmicrobialkilling),EffectorfunctionsofTH1cells,naiveCD4+Tcells,APC,Microbes,Proliferationanddifferentiation,Bcell,TH2cells,Eosinophil,Mastcelldegranulation,Activatedmacrophage,Suppressionofmacrophageactivation,Eosinophilactivation,Helminth(蠕虫),ProductionofIgE,ProductionofneutralizingIgGantibodies,IL-10,IL-4,IL-4,IL-5,EffectorfunctionsofTH2cells,Tc,NK,CTL,与,NK,细胞的比较,MHC/抗原肽提供杀伤信号,MHC分子提供杀伤抑制信号,病毒感染后期清除被病毒感染的细胞,病毒感染初期防止病毒扩散,RolfZinkernaglePeterDohertyNobelPrize1996,YouwontheNobelPrizeinMedicinein1996,fordiscoveringhowkillerT-cellsrec