医学免疫学英文版课件：T cell mediated immune response

T

cellmediatedimmuneresponseI.Adaptiveimmuneresponse1.ImmuneresponseAgPlasmacellTCellmediatdimmunityBAbHumoralimmunityfeatures：specificity,memoryActivatedT2.Processofimmuneresponse

stageofAgrecognition

stageofactivation,proliferationanddifferentiation

effect

stageII.StageofAgrecognitionsiteofimmuneresponseAgBTAPC肽

MHCMHCrestrictionImmunologicalsynapseIII.Stageofactivation,proliferationanddifferentiation1.ActivationofCD4+Tcell“Dual-signaltheory”T“1”“2”activation,proliferationdifferentiationeffectorcellmemorycell（clonalexpansion）2.SignaltransductionduringTcellactivationPTK 蛋白酪氨酸激酶 PLC-γ 磷酯酶C-γZAP-70 ζ链相关蛋白 PIP2 磷酯肌醇二磷酸SH2 Src同源区2 PKC 蛋白激酶CNFAT 激活T的核因子AP-1 激活蛋白—1NF-κB B细胞κ链转录因子（核因子κB）MAPK 丝裂原激活的蛋白激酶GEF 鸟苷酸置换因子TranscriptionalfactorIL-2R、IL-2IFN-IL-4、-5、-6、10CD40LFasLCTLA-4moleculecellActivation,differentiationClonalexpansionEffectorcellTmgeneactivation<YxxL/V>—ITAM—CD3PPTKZAP—70SH2RasG

proteinPLC-fosIP3DAGCa++PKCAP-1NFATNF-BGeneactivationtranscriptionB7-CD28MAPKinasePIP2TCRPTKLck FynCD4CD8—ITAM—CD3P•ITAM(Immunoreceptortyrosine-basedactivationmotif)twoYxxL/V

conservedsequence：Y--tyrosine，L—leucine，V—valineY-phosphorylation,thencombinewithcytoplasmicPTK(ZAP-70），transduceTCRacceptableantigenstimulationsignal3.Ag-specificTcellclonalexpansionanddifferentiationTCR-Ag：IL-2R（lowaffinity----highaffinity)CD28-B7：IL-2cellclonalexpansionActivationofCD8+TDual-signalNoco-stimulatemolecule，needproductionofIL-2byThcellIV.EffectstageEffectmechanismsofTh1cellActivatingMo-M，mediatinginflammation

*

IFN-、CD40L

activatingM，productionofIL-12，activatingTh1

*IL-3、GM-CSF

promotingproductionofM

*IL-1、IL-6、TNF、MCP-1

promotingMcrossvesselwall,mediatinginflammationTh1helplymphocyteIL-2:Th1,Th2,CTL,NKactivationandexpansionIFN-:IgG2aproductionTh1helpneutrophilLTandTNF-:neutriphilactivation,killingpathogen2.EffectmechanismsofTh2cell*humoralimmunityIL-4,5,10,13:promotingBcelldifferentiation,Abproduction*Participationofhypersensitivityandanti-parasiticimmunityActivatingmastcells,basophilsandeosinophils3.EffectmechanismsofTh17cell

*IL-17:stimulatingepithelialcells,endothelialcells,fibroblastsandmacrophagestosecreteavarietyofcytokines

*IL-8,MCP-1:recruitingneutrophilsandmonocytes

*G-CSF,GM-CSF:activatingneutrophilsandmonocytes

*IL-1,IL-6,TNF-,PGE2:mediatinginflammation4.EffectmechanismsofCTLkillingtargetcellspecificallyTargetcellActivatedTcTargetcellp-MHCp-MHC“APC”*recognitionstage、effectstageAgspecificityMHC

restriction（1）celllysis/apoptosis（perforin/granzyme）

（2）apoptosis:Fas/FasL,TNF医学免疫学上海第二医科大学免疫教研室医学免疫学上海第二医科大学免疫教研室MemoryTcellFaster,stronger,moreeffectiveimmuneresponse

CD45RO+，longevityCD4+Th1：mediatecellularimmuneresponse,

participateinEAE、RA、Cohn’sdisease。CD4+Th2：mediatehumoralimmuneresponse,participateinasthmaCD4+Th17：mediateinnateimmuneresponse，participateinearlyinflammationandRA,MS,

PsoriasisCD8+CTL：mediatecellularimmuneresponse，takepartintypeIVhypersensitivityandgraftrejectionReviewquestions:Describethedual-signaltheoryofTcellactivation.Explaintheter