医学免疫学-抗原加工递呈(英文)

AntigenPresentingCells&AntigenProcessingandPresentation

1ContentsAntigenPresentingCellsAntigenProcessingandPresentation2Immunobiology,5thediton,Janewayetal34AntigenPresentingCells(APCs):

APCsarecellpopulationsthatarespecializedtocapturemicrobialandotherantigens,displaythemtolymphocytes,andprovidesignalsthatstimulatetheproliferationanddifferentiationofthelymphocytes.AntigenPresentingCells5Classification:ProfessionalAPCs:DCs,Bcells,MNon-professionalAPCs:TargetcellsAntigenPresentingCells6Biologicalcharacteristics:constitutiveorinducibleexpression：MHCI,MHC-II,

co-stimulatorymolecules:B7-1/2

adhesionmoleculeschemokinereceptorsAntigenPresentingCells7Figure8-3ProfessionalAPCs:8Dendriticcells,

DCs：ProfessionalAPCs9PlasmacytoidDCs,pDCs

aretype-IIFN-producingcells.Theyareabletopromoteanti-viralinnateandadaptiveimmuneresponses.

ConventionalDCs,cDCs

areprofessionalAPCs.Theyareabletopromoteadaptiveimmuneresponses.(immatureandmaturecDCs)ProfessionalAPCs:DCs10ProfessionalAPCs:DCs11http://www.cd83.deProfessionalAPCs:DCs12ProfessionalAPCs:DCs1314Characteristics:constitutiveexpressionofMHCII,B7Distribution:perpherialblood,alltissuesexceptbrainIntakeofAg:phagocytosis,pinocytosis,receptor

mediatedProfessionalAPCs:DCs15ImmatureDCMatureDCIntakeofAg+++++MHC+++++B7+++++CD40+++++ProcessingofAg+++++PresentationofAg+/-++++SitesPeripheraltissuesSecondaryimmuneorgansAgmigrate16Biologicalfunction:

processingandpresentationofAgtonaïveT——primaryresponse

immunoregulation:secretecytokinesinduceimmunologicaltoleranceProfessionalAPCs:DCs17Monocytes/Macrophages(Mo/M)ProfessionalAPCs:M18activatedT,memoryT——secondaryresponse

constitutivelowexpressionofMHCIIinducibleexpressionofB7Distribution：differentorgansIntakeofAg:phagocytosis,pinocytosis,

receptormediated（FcR,CR）ProfessionalAPCs:M19B

cellsProfessionalAPCs:Bcells20

activatedT,memoryT——secondaryresponseconstitutivelowexpressionofMHCIIinducibleexpressionofB7IntakeofAg:pinocytosis,receptormediatedSurfacemarker：BCR-Igα/IgβProfessionalAPCs:Bcells21ProfessionalAPCs22Classification:ProfessionalAPCs:DCs,Bcells,MNon-professionalAPCs:Targetcells:AntigenPresentingCells23ContentsAntigenPresentingCellsAntigenProcessingandPresentation24Figure5-125ExogenousAgEndogenousAg26PathwayofAntigenPresentation:PresentationbyMHCclassⅠPresentationbyMHCclassⅡCrossPresentationofAntigensPresentationofNonproteinAntigensAntigenprocessingandpresentation27PresentationbyMHCclassⅠ:Presentintracellularorcytoplasmicantigens,whichnamedEndogenousAntigens.Antigenprocessingandpresentation28Ubiquitination:Endogenousantigens,whicharecytoplasmicproteins,targetedfordestructionarecovalentlytaggedwithubiquitin.Degradation:Proteinsbindingtoubiquitinaredestructedbyproteasomes.Antigenprocessingandpresentation29Proteasomeisalargeproteolyticenzymecomplexinthecytoplasm.Antigenprocessingandpresentation30Transportation:Proteasome-generatedpeptidesaretransportedtotheendoplasmicreticulumbyTAP1andTAP2(transporterassociatedwithantigenprocessing).Antigenprocessingandpresentation31Loading:Tapasin,associatedwithTAP,assistspeptidesloadingintothenewlysynthesizedMHCclassⅠ:2complexes.Moving:ThenewlyformedpMHCclassⅠcomplexesmovetotheGolgi.Antigenprocessingandpresentation32PresentationbyMHCclassⅠAntigenprocessingandpresentation33Buddingoff:ExocyticvesiclescontainingpMHCclassⅠbudofffromtheGolgiandarerapidlytransportedtothecellsurface.Display:pMHCclassⅠcmplexesdisplayandrecognitionbytheappropriateCD8+Tcells.Antigenprocessingandpresentation34Agprocessingpathway-MHCclassI35PresentationbyMHCclassⅡ:Presentextracellularantigens,whichnamedExogenousAntigens.Antigenprocessingandpresentation36Uptake:Exogenousantigensenterthecellbyphagocytosisorpinocytosispackagedinphagocyticvesicles.DegradationPhagocyticvesiclesfusewithlysosomestoformphago-lysosomes.Theingestedmaterialisdegradedintopeptidesinthelatephagosome.Antigenprocessingandpresentation37MHCclassⅡmoleculeswithinvariantchainareassembledintheendoplasmicreticulum.BudofffromtheendoplasmicreticulumtoformMHCclassⅡ-richvesicles.Fusion:Latephagosomefuseswiththe

vesiclecontainingMHCclassⅡ.Iaassociatedinvariantchain,IichainAntigenprocessingandpresentation38Iichaindisintegration:Theacidicenvironmentofthevesiclecausestheinvariantchaintocleave.Antigenprocessingandpresentation39Theinvariantchainiscleavedtoleaveapeptidefragment,CLIP,boundtotheMHCclassIImolecule.CLIPAntigenprocessingandpresentation40Loading:HLADMassiststhepeptidetooccupythepeptide-bindinggrooveoftheMHCclassⅡmolecule.Antigenprocessingandpresentation41Display:ThevesiclescontainingpMHCclassⅡfusewiththecellmembraneandpMHCclassⅡaredisplayedandrecognitionbyCD4+Tcell.Antigenprocessingandpresentation42Agprocessingpathway