分子免疫学T细胞免疫应答机制2014硕士.ppt

,识别,活化,效应,免疫应答的三个阶段,OverviewofgenerationofTcellandTcellresponsesinvivo,Typesofadaptiveimmuneresponses,.,Tcellsubsets,Typesofcell-mediatedimmunereactions,CD4+ThresponsesCD8+CTLresponses,Delayed-typeHypersensitivity(DTH)Tcell-dependentimmunereactionsthatcausenormaltissuesinjury,NKcellmediatedinnateimmunity,killinfectedcellearly,CD4+Th1responsesmicrobesresidingwithinthephagosomesofphagocytesCD8+CTLresponsesmicrobesresidinginthecytoplasmofvariouscelltypesCD4+Th2responseshelminthicparasitesCD4+Th17responsesextracellularbacteria,fungi.,DifferenttypesofmicrobeselicitdistinctprotectiveTcellresponses,DefectsinCMIresultinincreasedsusceptibilitytoinfectionbyvirusesandintracellularbacteria,TypesofTcell-mediatedimmuneresponse,MajormediatorsofTcell-mediatedimmuneresponses,CytokinesMembraneproteinsTNFfamilymembers:CD40L,TNF-,FasL,Th1-MediatedImmuneResponses,ThephysiologicalroleofTh1cellsphagocyte-mediateddefenseagainstinfections,especiallywithintracellularmicrobesPathologicalrolesofTh1cellManyorgan-specificautoimmunediseasesandinflammatoryreactionsareduetoexcessiveactivationofTh1cells,EffectorfunctionsofTh1cells,Tcellsignalsthatactivatemacrophages,IFN-CD40L-CD40interactions,CentralroleofTh1intheactivationofmacrophage,IFN-,Themajorsources:Th1,CD8+TcellsThemajormacrophage-activatingcytokineStimulatesthemicrobicidalactivitiesofphagocytesStimulatestheproductionofIgGAbstopromotethephagocytosisofmicrobes,CD40L/CD40,Delivercontact-mediatedsignalsactivatesthetranscriptionfactorsnuclearfactorKB(NF-KB)andactivationprotein-1(AP-1)IncreasestheresponsetoIFN-ClinicalevidenceHumanswithinheritedmutationsinCD40L(X-linkedhyper-IgMsyndrome):severedeficienciesinCMItointracellularmicrobes,Theeffectorfunctionsofactivatedmacrophages,KillingofphagocytosedmicrobesBecomethemoreefficientAPCsStimulationofacuteinflammationTissueRepair,ActivationandfunctionsofmacrophagesinCMI,Th2-MediatedImmuneResponses,ThephysiologicalroleofTh2cellsEliminationofhelminthicinfectionPathologicalrolesofTh2cellTheunderlyingcauseofallergicreactions,EffectorfunctionsofTh2cells,Promotionofantigen-specificIgEproductionActivationofeosinophilsandmastcellsAlternativemacrophageactivationBarrierimmunitybyTh2cytokine,EffectorfunctionsofTh2cells,TheeffectorfunctionofTh2cytokines,IL-4andIL-13Stimulatetheproductionofantigen-specificIgEAlternativelyactivatemacrophagesIL-4promotesexpulsionofmicrobeswhileIL-13stimulatesmucussecretionIL-5Recruitandactivateeosinophils,TheorchestrationofmacrophageactivationandpolarizationbyThcells,BiswasS,etal.NatureImmunol,2010,ThephysiologicalroleofTh17cellsProtectionagainstextracellularbacterialandfungalinfectionsPathologicalrolesofTh17cellmaybeimportantinmeditatingtissuedamageinimmune-mediatedinflammatorydiseases,e.g.autoimmunediseases,Th17-MediatedImmuneResponses,Th17-specificcytokines,IL-17AIL-17FIL-22,EffectsofInterleukin-17onCellFunctionsandItsRoleinthePathophysiologyofDiseases.,IL-22,Proinflammatoryandprotectiveproperties,Proinflammatoryroleinpsoriasis,RAandsomeinfection,ProtectiveroleinIBD,infection,andliverinjury,OConnorJretal.NatureImmunol2010,AsimplifiedmodelforpleiotropicTH17cytokinesincoordinatinginflammation,protection,Chronicinflammation,BettelliE,TKorn,MOukka,andVKKuchroo.InductionandeffectorfunctionsofTH17cells.Nature453:1051-1057,2008DongC.TH17cellsindevelopment:anupdatedviewoftheirmolecularidentityandgeneticprogramming.NatureReviewsImmunology8:337-348,2008.FarrarJD,HAsnagli,andKMMurphy.Thelpersubsetdevelopment:rolesofinstruction,selection,andtranscription.JournalofClinicalInvestigation109:431-435,2002.KornT,EBettelli,MOukka,andUKKuchroo.IL-17andTh17cells.AnnualReviewofImmunology27,2009McGeachyMJ,andDJCua.Th17celldifferentiation:thelongandwindingroad.Immunity28:445-453,2008.OuyangW,JKKolls,andYZheng.ThebiologicalfunctionsofThelper17celleffectorcytokinesininflammation.Immunity28:454-467,2008.,Selectedreadings,CytotoxicTLymphocytes(CTLs),EffectorCD8+TCellsEliminateintracellularmicrobesmainlybykillinginfectedcells,CTLinducetheapoptosisoftargetcells,AntigenspecificOnlykilltargetsthatexpressthesameclassI-associatedantigenthattriggeredtheirdifferentiationfromnaveCD8+TcellContactdependentTheformationofimmunologicalsynapseThespecificdeliveryofthemolecules,CTL-mediatedcytotoxcity,StepsinCTL-mediatedlysisoftargetcells,antigenrecognition,activationoftheCTLs,deliveryofthelethalhitthatkillsthetargetcells,releaseoftheCTLsfromtargetcell,StepsinCTL-mediatedlysisoftargetcells,MechanismsofCTL-mediatedlysisoftargetcells,GranuleexocytosisFas/FasLpathway,Onlyhuman,Perforinapore-formingproteinmoleculeMainfunctionistofacilitatedeliveryofthegranzymesintothecytosolofthetargetcellGranzymes(granuleenzymes)Serineproteases,includingA.B.CGranzymesBinitiateapoptoticpathwaysinvolvecaspases.,ThetwoimportantgranuleproteinsforCTLkillingfunction,MechanismsofCTL-mediatedlysisoftargetcells,CytokinessecretedbyCTL,IFN-TNF-TNF-,ThedifferenttypesofeffectorTcellsubsetsproducedifferenteffectormolecules,IL-22,BossiG,andGMGriffiths.CTLsecretorylysosomes:biogenesisandsecretionofaharmfulorganelle.