T细胞亚群(最好的、漂亮免疫)PPT课件

.,1,T细胞亚群,何睿ruihe免疫学系上海医学院复旦大学,.,2,.,3,.,4,Classesoflymphocytes,.,5,T细胞亚群T细胞活化分子机制T细胞免疫应答及其效应,自身免疫和超敏反应,.,6,Tcellsubsets,TcellsandTcellsCD4+TcellsandCD8+TNaveTcells（初始T细胞）EffectorTcells（效应T细胞）MemoryTcells（记忆T细胞）Thelper(Th)辅助性CD4+T细胞CytotoxicTcells(CTLs)细胞毒性CD8+T细胞RegulatoryTcells(Tregs)调节性CD4+T细胞,.,7,TCellsubsets,.,8,Tcells,expressalimitednumberofTCRsabundantinepithelialtissuesofcertainspecies:inthesmallbowelmucosaandintheskinofmouse.Intheskin,knownasadendriticepidermalTcell(DETC)donotrecognizeMHC-associatedpeptideantigensandarenotMHCrestricted.maybindtoconservedligandswhoseexpressionistriggeredbycellinjuryorstress,suchasmicrobialheatshockproteins.mayrepresentanimportantbridgebetweeninnateandadaptiveimmunity,functioningaslymphocytesthatenhancethefirstlineofdefenseagainstarangeofpathogens.,.,9,Jensen,K.D.etal.ThymicselectiondeterminesTcelleffectorfate:antigen-naivecellsmakeinterleukin-17andantigen-experiencedcellsmakeinterferonImmunity29,90100(2008).,EpithelialTcellandPeripheralTcellCD27-IL-17+TcellsandCD27+IFN-+Tcells,SubsetsofTcells,.,10,DevelopmentalprogrammingofTcellsubsets.,CuaDJ,etal.NaturereviewImmunology,2010,.,11,MartinBetal.IL-17-ProducingTcellsSelectivelyExpandinResponsetoPathogenProductsandEnvironmentalSignals.Immunity31,321330(2009).TheyshowthatT-17cellsadditionallyexpressIL-23R,andtheinnatereceptorsTLR2anddectin-1,whichrecognizearchetypicalandfungalconstituents.TheseT-17cellsusethesereceptorstorapidlyproduceIL-17inresponsetobystandercell-derivedIL-23andtobacteriaandfungiwithoutconcomitantTCRstimulation.OneoftherolesofT-17-derivedmaybeindirectordirectamplificationofIL-17productioninTh17cells.Sutton,C.E.etal.Interleukin-1andIL-23induceinnateIL-17productionfromTcells,amplifyingTh17responsesandautoimmunity.Immunity31,331341(2009).ThisreportshowsthatTcellshaveanearlyroleinpromotingCNSinflammation.Theauthorssuggestthatinnatecell-producedIL-17directlyenhancesdevelopmentofMOG-specificTh17cells.,AmajorinnatesourceofIL-17,.,12,InnateActivationofIL-17-ProductionbyaSpecializedTCellSubset,KapsenbergML.Immunity,2009,.,13,Witherden,etal.ThejunctionaladhesionmoleculeJAMLisacostimulatoryreceptorforepithelialTcellactivation.Science2010SepIdentifyanepithelialTcells-specificcostimulatorymolecule,JAMLPetermannF,etal.TcellsenhanceautoimmunitybyrestrainingregulatoryTcellsresponsesviaanIL-23-dependengmechanism.Immunity,2010SepIL-23-activatedrendereffectorTcellsrefractorytothesuppressiveactivityofTregcellsandalsopreventedtheconversionofconventionalTcellsintoFoxp3+Tregcellsinvivo.,TwonewpapersaboutTCellpublishedinthismonth,.,14,.,15,NaveTcellsMatureTcellsthathavenotpreviouslyencounteredantigen;Preferentialmigrationtosecondarylymphoidorgans(lymphnodes),wheretheyrecognizeantigenEffectorTcellsActivatedTcellscapableofperformingthefunctionsrequiredtoeliminateforeignantigensPreferentialmigrationtositesofinfectionorinflammationShort-livedMemoryTcellsLong-lived,functionallysilentcells;MountrapidsecondaryimmuneresponsestothesameantigenexposureHeterogenous(centralandeffector),BasedonthehistoryofantigenencounterandthestageofTcellactivation.,.,16,.,17,CentralmemoryTcellsexpressCCR7andL-selectin,andhometolymphnodes.limitedcapacitytoperformeffectorfunctionswhentheyencounterantigengeneratemanyeffectorcellsuponantigenchallengeEffectormemoryTcellsdonotexpressCCR7orL-selectin,andhometoperipheraltissues,duceeffectorcytokinesuponantigenicstimulationdonotproliferatemuch.,Basedontheirhomingpropertiesandeffectorfunctions.,SubsetsofmemoryTcells,.,18,CD4+,CD8+,CD4+,.,19,Th1-Th2hypothesis1986CoffmanandMossmanTh172006,DiscoveryofCD4+Thcellsubsets,.,20,ThesubsetsofCD4+Thcells,Howtheyareinduced,WhatcytokinestheyproduceWhateffectormechanismstheyactivate,Th0,.,21,Cytokines,StimulithatinfluencethepatternofThcelldifferentiation,HighdosesofantigenwithoutadjuvantsDifferentsubsetsofdendriticcellsmayexistThegeneticmakeupofthehost,.,22,PropertiesofCD4+Th1andTh2subsets,.,23,DifferentiationofTh1Subset,StimulatedbyintracellularmicrobesthatinfectoractivatemacrophagesorNKcellsListeria,mycobacteriaandLeishmania,ImportantcytokinesfortheTh1differentiation,Importanttranscriptionfactors(TF)fortheTh1differentiation,IL-12IFN-IL-18typeIIFNs(inhuman),T-bet:masterregulatorSTAT4STAT1,.,24,ThemolecularbasisofTh1differentiation,TheinterplayofsignalsfromtheTcellreceptor,thecytokinesIFN-andIL-12,andtheTFT-bet,STAT1,andSTAT4,IL-12STAT-4IFN-STAT-1AgrecognitionbyTCRT-betApositiveamplificationloopbetweenT-betandIFN-,.,25,DifferentiationofTh1subsets,.,26,DifferentiationofTh2Subset,ImportantTFfortheTh2differentiation,StimulatedbymicrobesandantigensthatcausepersistentorrepeatedTcellstimulationwithlittleinflammationormacrophageactivationHelminthandallergens,ImportantcytokinesfortheTh2differentiation,IL-4,GATA-3:masterregulatorSTAT6,.,27,ThemolecularbasisofTh2differentiation,TheinterplayofsignalsfromtheTcellreceptor,thecytokineIL-4,andtheTFGATA-3andSTAT6,.,28,GATA-3,EnhancesexpressionoftheTh2cytokinegenesIL-4,IL-5,andIL-13by1)directlyinteractingwiththepromotersofthesegenes2)causingchro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