浙江大学医学免疫学经典课件免疫11-apc

Antigen-PresentingCellsandAntigenPresentatio[e-mail]IntroductionAntigen-presentingcellsAntigenprocessingandpresentationContentsI.Antigen-presentingcell,APCAntigen-presentingcellsarerequiredforTcellactivationAvarietyofcellsspecializedincapturing、processingandpresenttheantigentotheTlymphocytes,causingeithertoleranceorimmunity.ThesecellsarenameasAnitgenpresentingcell,APCDendriticcells,monocytes/macrophagesandBcellsareprofessionalAPCs.I.Antigen-presentingcell,APCAPC染色彩图Antigen-presentingcellsDendriticcellsMacrophagesBcellsNon-professionalAPCEndothelialcell(EC)FibroblasticcellActivatedTcellUndersomecircumstances,theycanexpressMHCIIandpresentAgsII.AntigenpresentationTheprocessbywhichAPCexpresspeptide-MHContheircellsurfaceinaformrecognizablebylymphocytes.Antigen-presentingcellsI.DendriticcellshighlybranchedmorphologycanactivenaiveTcellsmarkersTheNobelPrizeinPhysiologyorMedicine2011拉尔夫·斯坦曼（RalphM.Steinman）【已故】1943年出生于加拿大蒙特利尔，在麦吉尔大学学习生物学和化学。之后在美国哈佛医学院学习医学，1968年获得医学博士学位（MD）。于1970年被纽约洛克菲勒大学接纳，从1988年起成为免疫学教授。担任该校免疫学与免疫性疾病中心主任。发现树突状细胞Dendriticcells,DC是启动适应性免疫应答的关键细胞R.M.SteinmanandZ.A.Cohn.J.Exp.Med.137,1142–1162;19731.SurfacemarkersMHCclassI/IImoleculesCD1a,CD11c,CD83(human)33D1,NLDC145(mouse)Co-stimulatorymolecules:B7.1(CD80)/B7.2(CD86),CD40,CD44,CD542.SourcesofDC单核细胞巨噬细胞中性粒细胞B细胞T细胞NK细胞髓系DCBTNK髓系DC淋巴系DC淋巴系前体细胞髓系前体细胞多能造血干细胞GM-CSFTNF-aIL-4HSCMyeloidprogenitorLymphoidprogenitorMyeloidDCMomacrophageMyeloidDCPMNLymphoidDC3.DistributionandClassificationofDCDCsarefoundinmanyorgansthroughoutthebodyDCinlymphoidtissue-LymphoidtissueDCInterdigitatingcell,IDCFollicularDC,FDCthymicdendriticcell,TDCDCnotinlymphoidtissue-Non-lymphoidtissueDCLangerhanscellsInterstitialDCDCinbodyfluid-CirculatingDCVeiledcellsPeripheralbloodDCLocatedinlymphfollicleswhicharerichinBcells;DerivedfrominterstitialDC;HighlyexpressFcR,CR1andCR2;InvolvedinthegenerationandmaintenanceofmemoryBcells.1)FollicularDC(FDC)FollicularDC,FDCBcellsFDCFDCexpresshighlevelsofmembranereceptorsforantibodyandcomplement.Bythese,FDCactivestheBcellsinlymphnodes.2)InterdigitatingDC(IDC)MainAPCtoinduceprimaryimmuneresponse;DerivedfromLangerhanscells;FcR-andC3bR-,MHCIandIIhigh;DistributedmainlyintheTcellareaofsecondarylymphoidtissue,presentAgstoTcells.3)Langerhanscells(LC)Foundintheepidermis(skin)andmucousmembranes;MHCIandIIhigh,highlyexpressFcRandC3bR,Birbeckparticle(duetolangerinexpression);PowerfulabilitytocaptureandprocessAgsandmigrationtolymphnodeafteractivation.LangerhansIDC4.DevelopmentofmyeloidDCFourphasesPre-DCMonocyte,MoImmatureDCUptakeantigenMigrationMatureDCExpresshighlevelsofMHCIandII,CD80,CD86,CD40,CD54,HSP,etc.ImmatureDCPhenotype:highexpressionofreceptorsrelatedtophagocytosis(FcR,CR,mannosereceptor,DC-sign);lowexpressionofCD54,CD40,CD80;CD86andMHCII,CD14-Function:1)strongcapacitytoingestandprocessAgs,butweakabilitytopresentAgs2)inductionofimmunetolerance3)sensingofinfectiousagentsbyTLR(patternrecognitionreceptors)MatureDCPhenotype:lowexpressionofreceptorsrelatedtophagocytosis(FcR,CR,mannosereceptor);highexpressionofCD54,CD40,CD80,CD86andMHCII;CD83+andCD25+Function:weakabilitytocaptureandprocessAgs,powerfulabilitytopresentAgs.DendriticCellMaturationMHCII5.DCinimmuneactivationandimmunetolerance1)DCinimmuneactivationPresentantigenandactivateTcells①ThefirstsignalMHCII-Ag:CD4+TcellsMHCI-Ag:CD8+Tcells②Thesecondsignalco-stimulatingmoleculescytokinesIL-12Peripheraltolerance:immatureDCcaptureautoantigenwhentheymigratefromnon-lymphoidtissuetoTcellareaofsecondarylymphoidtissue,andinduceperipheraltolerance.Centraltolerance:inducedinnegativeselectionofTcellsinthethymus.2)DCinduceimmunetoleranceBonemarrowBloodTissueHSCMyeloidprogenitorPre-monocyteMonocyteMonocyteMacrophageIIMononuclearphagocytesystem(MPS)1.DifferentiationanddistributionDifferentnamesindifferenttissuesMonocyte(blood)Kupffercells(liver)Mesangialcells(kidneyglomerulus)Microglia(brain)Alveolarmacrophages(lung)Histiocyte(connectivetissue)MHC-IandIImolecules;CAM:LFA-1,ICAM-1,B7,CD40;FcR;CR:CR1,CR3,CR4;Pattern-recognitionreceptor(PRR):mannosereceptor,scavengerreceptor(CD91),Toll-likereceptors2.Surfacemarkers3.BiologicalfunctionsofMAntigenprocessingandpresentationphagocytosispinocytosisreceptor-mediatedendocytosisAntimicrobialandcytotoxicactivity:anumberofantimicrobialandcytotoxicsubstancesproducedbyactivatedMcandestroyphagocytosedmicroorganisms.Reactiveoxygenintermediates,nitricoxide.Secretionofsolublefactors:enzymes:lysozyme,myeloperoxidase,etc.cytokines:IL-1,IL-6,TNF,IL-12,IL-18,etc.complement:C1~C9,Bfcoagulationfactors,PG,LTs,ACTH,etc.phagocytosismacrophageAgpresentationMacrophagesTakeUpAntigenMacrophagesTakeUpAntigenIntoVesiclesandPresentPeptideIntoVesiclesandPresentPeptideFragmentsFromProteinsFragmentsFromProteinsinMHCinMHC--IIIIIII.Bcellsbonemarrow-dependentlymphocyteAbout5-15%ofthecirculatinglymphoidpoolareBcellsdefinedbythepresenceofsurfaceimmunoglobulin(Ig).III.BcellsBCells(BCR)T