医学免疫学09细胞免疫应答.ppt

获得性细胞免疫应答,9AcquiredCellularResponse,Peripherallymphoidorgansandimmunerecognition(外周淋巴器官与免疫识别),启动阶段AgprocessingandpresentationTcellstimulation-activation增殖Tcellactivationandproliferation效应阶段EffectorTcells调节复原Immunoregulation,9-1获得性免疫应答的基本过程,9-2DC启动获得性免疫应答,9-3T细胞的活化,9-3-1T-APCInteraction,T细胞与APC的附着,TCR扫描APC表面,9-3-2ecognitionofMHC/peptidecomplexbyTCR,TCR抗原结合部位,抗原的特异性识别,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,9-3-3T细胞活化的“双信号模型”,T细胞活化过程中的信号转导,9-4抗原特异性淋巴细胞的克隆扩增与选择,9-5EffectorTCells(效应T细胞),辅助性T细胞：Th1与Th2,Tc细胞,效应T细胞的调节,再次免疫应答,CD4+,CD8+,CD4+25+,2hrsWashx3,1hrsWashx3,51Cr,4hrs37,BCL,MeasureSpecific51Cr-Release,+Virus,Experimentalprocedurefortestingantigen-specificCTLactivity,Tcells,Harvestsupernatant,9-6效应T细胞的MHC限制性,RolfZinkernaglePeterDohertyNobelPrize2019,AgSpecificity,9-7AdhesionmoleculesandImmigrationoflymphocytes,淋巴细胞循环途径,9-8Immunologicalmemory,MemoryTCells:RestingstateLonglived(continuouslyrenewal)Easilytriggered(donotneedco-stimulatorymolecules)Responsibleformaintainingimmunologicalmemory,9-8获得性免疫应答的调节,神经内分泌系统对免疫系统的调节作用,抗原对免疫应答的调节作用,活化诱导的细胞死亡（CTLA4）,调节性T细胞,转导负性信号的免疫细胞膜分子,CD4+CD25+RegulatoryTcells,AuniquelineageofregulatoryTcellscapableofmaintainingselftoleranceinvivo,T,CD8,CD4,CD4+25+,Th1,Tc2,Tc1,Th2,Th3,Tr1,PeripheralTlymphocyte,5-10%,30%,Th4?,60%,Thymus,CD4,Effectors,Regulators,Normalmouse,CD4+T-cellsuspensionseliminatedofCD25+cells,Tcell-deficientmouse,AutoimmunediseasesthyroidstomachsalivaryglandLangerhansisletsadrenalglandsovariestestes,CD4+CD25+Trcells:Comprise5-10%ofperipheralCD4TcellsinhumanandmiceProducedinthymusasanuniquelineageofCD4TcellsSecretIL-10and/orTGF-b,butlittleIL-2Anergicandsuppressive,CD45RBlow,CTLA-4high,MaintainimmunologicaltoleranceInhibitproliferationofCD4+CD25-Tcellsinvitro,needactivationviaTCRandcell-cellcontacttofunction,butIL-10andTGF-bmayalsoparticipate,SuppressivecapacitycouldbereversedbyaddingexogenousIL-2,byusinganti-CD28mAb,FunctionofCD4+CD25+Tcells,Anti-idiotypicnetworkSurfacemoleculestransducinginhibitoryorapoptosissignalsRegulatoryTcellsTscellsAnti-idiotypicTcellsTh1,Th2,Th3,Tr1CD4+25+,CD4+Tcellsarethemaintargetsofimmunoregulation,RegulatoryTcel