醫(yī)學(xué)免疫學(xué)-T細(xì)胞免疫應(yīng)答及其效應(yīng)

T細(xì)胞免疫應(yīng)答及其效應(yīng)

免疫學(xué)系

1識(shí)別活化效應(yīng)免疫應(yīng)答的三個(gè)階段2OverviewofgenerationofTcellandTcellresponsesinvivo

3應(yīng)答誘導(dǎo)淋巴器官內(nèi)抗原識(shí)別T細(xì)胞擴(kuò)增和分化分化的細(xì)胞進(jìn)入循環(huán)效應(yīng)T細(xì)胞和其他白細(xì)胞遷移到感染部位在外周效應(yīng)T細(xì)胞遭遇抗原效應(yīng)T細(xì)胞活化T細(xì)胞的效應(yīng)功能4Typesofadaptiveimmuneresponses5.Tcellsubsets6Typesofcell-mediatedimmunereactionsCD4+ThresponsesCD8+CTLresponsesDelayed-typeHypersensitivity(DTH)Tcell-dependentimmunereactionsthatcausenormaltissuesinjuryNKcellmediatedinnateimmunity,killinfectedcellearly7CD4+Th1responsesmicrobesresidingwithinthephagosomesofphagocytes

CD8+CTLresponsesmicrobesresidinginthecytoplasmofvariouscelltypes

CD4+Th2responses

helminthicparasites

CD4+Th17responsesextracellularbacteria,fungi…..DifferenttypesofmicrobeselicitdistinctprotectiveTcellresponsesDefectsinCMIresultinincreasedsusceptibilitytoinfectionbyvirusesandintracellularbacteria

8MajormediatorsofTcell-mediatedimmuneresponsesCytokinesMembraneproteins

TNFfamilymembers:CD40L,TNF-,FasL9Th1-MediatedImmuneResponses

ThephysiologicalroleofTh1cells

phagocyte-mediateddefenseagainstinfections,especiallywithintracellularmicrobes

PathologicalrolesofTh1cellManyorgan-specificautoimmunediseasesandinflammatoryreactionsareduetoexcessiveactivationofTh1cells10EffectorfunctionsofTh1cells1112Tcellsignalsthatactivatemacrophages

IFN-

CD40L-CD40interactions

CentralroleofTh1intheactivationofmacrophage13IFN-Themajorsources:Th1,CD8+TcellsThemajormacrophage-activatingcytokineStimulatesthemicrobicidalactivitiesofphagocytesStimulatestheproductionofIgGAbstopromotethephagocytosisofmicrobes14CD40L/CD40Delivercontact-mediatedsignals

activatesthetranscriptionfactorsnuclearfactorKB(NF-KB)andactivationprotein-1(AP-1)IncreasestheresponsetoIFN-ClinicalevidenceHumanswithinheritedmutationsinCD40L(X-linkedhyper-IgMsyndrome):

severedeficienciesinCMItointracellularmicrobes15TheeffectorfunctionsofactivatedmacrophagesKillingofphagocytosedmicrobesBecomethemoreefficientAPCsStimulationofacuteinflammationTissueRepair16ActivationandfunctionsofmacrophagesinCMI17Th2-MediatedImmuneResponsesThephysiologicalroleofTh2cells

EliminationofhelminthicinfectionPathologicalrolesofTh2cellTheunderlyingcauseofallergicreactions18EffectorfunctionsofTh2cellsPromotionofantigen-specificIgEproductionActivationofeosinophilsandmastcells

AlternativemacrophageactivationBarrierimmunitybyTh2cytokine19EffectorfunctionsofTh2cells20TheeffectorfunctionofTh2cytokinesIL-4andIL-13

Stimulatetheproductionofantigen-specificIgEAlternativelyactivatemacrophagesIL-4promotesexpulsionofmicrobeswhileIL-13stimulatesmucussecretionIL-5

Recruitandactivateeosinophils21TheorchestrationofmacrophageactivationandpolarizationbyThcellsBiswasS,etal.NatureImmunol,201022ThephysiologicalroleofTh17cells

ProtectionagainstextracellularbacterialandfungalinfectionsPathologicalrolesofTh17cellmaybeimportantinmeditatingtissuedamageinimmune-mediatedinflammatorydiseases,e.g.autoimmunediseasesTh17-MediatedImmuneResponses23Th17-specificcytokinesIL-17AIL-17FIL-2224EffectsofInterleukin-17onCellFunctionsandItsRoleinthePathophysiologyofDiseases.25IL-22ProinflammatoryandprotectivepropertiesProinflammatoryroleinpsoriasis,RAandsomeinfectionProtectiveroleinIBD,infection,andliverinjury26O'ConnorJretal.NatureImmunol2010AsimplifiedmodelforpleiotropicTH17cytokinesincoordinatinginflammationprotectionChronicinflammation27BettelliE,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.Selectedreadings28CytotoxicTLymphocytes(CTLs)EffectorCD8+TCellsEliminateintracellularmicrobesmainlybykillinginfectedcells29CTLinducetheapoptosisoftargetcells30

Antigenspecific

OnlykilltargetsthatexpressthesameclassI-associatedantigenthattriggeredtheirdifferentiationfromna?veCD8+Tcell

Contactdependent

TheformationofimmunologicalsynapseThespecificdeliveryofthemoleculesCTL-mediatedcytotoxcity31StepsinCTL-mediatedlysisoftargetcellsantigenrecognition,activationoftheCTLs,deliveryofthe"lethalhit"thatkillsthetargetcells,releaseoftheCTLsfromtargetcell32StepsinCTL-mediatedlysisoftargetcells33MechanismsofCTL-mediatedlysisoftargetcells

GranuleexocytosisFas/FasLpathwayOnlyhuman34Perforin

apore-formingproteinmoleculeMainfunctionistofacilitatedeliveryofthegranzymesintothecytosolofthetargetcellGranzymes(granuleenzymes)Serineproteases,includingA.B.CGranzymesBinitiateapoptoticpathwaysinvolvecaspases.Thetwoimportant