浙江大学医学免疫学经典课件03-antigen

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Antigen(Ag)第二章抗原ChapterⅡAntigen1.Concept2.Immunogenicityandspecificity3.Requirementsforimmunogenicity4.Typesofantigens5.SuperantigenandadjuvantsKNOWLEDGEPOINTSConcept1.Antigen(Ag)–thesubstancesthatarerecognizedbyTCR/BCRorantibodyandinduceaspecificimmuneresponse.Antigen2.PropertiesofAg-⑴immunogenicity-⑵antigenicityorimmunoreactivity(reactwiththeproductsofaspecificimmuneresponse)AgTBT浆细胞致敏T细胞抗体免疫原性AgTBT浆细胞致敏T细胞抗原性抗体3.Immunogen-Asubstancethatinducesaspecificimmuneresponse.CompleteAgs:havethepropertiesofimmunogenicityandimmunoreactivity.Hapten(半抗原):havethepropertyofimmunoreactivitybutnotimmunogenicity.-Asubstancethatisnon-immunogenicbutwhichcanreactwiththeproductsofaspecificimmuneresponse.AntigenHaptensaresmallmoleculeswhichcouldneverinduceanimmuneresponsewhenadministeredbythemselvesbutwhichcanwhencoupledtoacarriermolecule.hapten+carrier→completeAg5.Tolerogen,allergenTolerogen:anantigenthatinducesastateofspecificimmunologicalunresponsivenessAllergen:asubstancecapableofinducingallergyorspecifichypersensitivity.pollens,dust,drugs,andfoods…AntigenForeignnessandspecificityⅠ.Foreignness-Theimmunesystemnormallydiscriminatesbetweenselfandnon-selfsuchthatonlyforeignmoleculesareimmunogenic.Ⅱ.specificity1.epitope(antigenicdeterminant)抗原决定簇(基),表位-theportionoftheantigenthatbindsspecificallywiththebindingsiteofanantibodyorareceptoronalymphocyte.-thesizeofanepitopeisapproximatelyequivalentto5-15aminoacids.AntigenepitopeAntigendescriptionexampleOneepitopehaptensManyepitopesofthesamespecificityManypolysaccharides,homopolymersManyepitopesofdifferentspecificityproteinsRepresentationofsomepossibleantigenicstructures2.thetypesofepitope▲conformationalepitope:Someepitopesformonlywhenthecriticalresiduesarebroughttogetherinspacethroughfoldingofthepolypeptideorpolysaccharidechainintoitsnormalthree-dimensionalconformation.▲sequentialepitope:Alloftheaminoacidorsugarresiduesthatformagivenepitopearepositionedsequentiallyinthelinearsequenceofaproteinorpolysaccharideantigen.AntigenBindingsiteforantigenBindingsiteforantigen构象表位线性表位★Bcellepitope★TcellepitopeAntigenAntigenTcellepitopeBcellepitope●ReceptorTCRBCR●APC,MHCnecessaryunnecessary●Characterlinearshortnaturalpolypeptidepeptidepolysaccharideslineardeterminantconformationaldeterminant;lineardeterminant●LocationAgsurfaceofAgAntigen3.epitope-carriereffectAntigenAntigen4.commonantigenandcross-reactionFactorsinfluencingimmunogenicityA.Contributionoftheantigen1.chemicalComposition–proteinpolysaccharidenuclearacid2.size-Thereisnotabsolutesizeabovewhichasubstancewillbeimmunogenic.Ingeneral,thelargerthemoleculethemoreimmunogenicitislikelytobe.Antigen3.chemicalcomplexity-Ingeneral,themorecomplexthesubstanceischemicallythemoreimmunogenicitwillbe.Anincreaseinthechemicalcomplexityofacompoundisaccompaniedbyanincreaseinitsimmunogenicity4.conformation5.accessibility6.physicalform-Ingeneralparticulateantigensaremoreimmunogenicthansolubleones.AntigenAntigenB.Contributionofthehost1.GeneticFactors-Somesubstancesareimmunogenicinonespeciesbutnotinanother.Similarly,somesubstancesareimmunogenicinoneindividualbutnotinothers(i.e.respondersandnon-responders).2.Age-Agecanalsoinfluenceimmunogenicity.Usuallytheveryyoungandtheveryoldhaveadiminishedabilitytomountandimmuneresponseinresponsetoanimmunogen.AntigenC.MethodofAdministration1.Dose-Thedoseofadministrationofanimmunogencaninfluenceitsimmunogenicity.2.Route-Generallythesubcutaneousrouteisbetterthantheintravenousorintragastricroutes.Therouteofantigenadministrationcanalsoalterthenatureoftheresponse3.AdjuvantsAntigenTypesofantigensTh:Thymus-dependentantigen(TD-Ag)Thymus-independentantigen(TI-Ag)Relative:XenogenicantigenAllogenicantigenAutoantigenHeterophilicantigenIdiotypicantigenAntigenTD-AgThymus-dependentantigensarethosethatdonotdirectlystimulatetheproductionofantibodywithoutthehelpofTcells.Bcellepitope+TcellepitopeHumoralimmunityandcellularimmunityAntibody:fivetypesImmunememoryProteinsarethymus-dependentantigens.AntigenTI-AgThymus-independentantigensareantigenswhichcandirectlystimulatetheBcellstoproduceantibodywithouttherequirementforTcellhelpIngeneral.onlyBcellepitopeHumoralimmunityAntibody:IgMNoImmunememorypolysaccharidesareTI-antigens.AntigenTI-AgThymus-independentantigenscanbesubdividedintoType1andType2basedontheirabilitytopolyclonallyactivateBcells.Type1TI-Ag(LPS)arepolyclonalactivatorswhileType2arenot.AntigenXenogenicAg-Anantigenfoundinmorethanonespecies.AllogenicAg-individualsofaspeciesdifferinalleles(areallogeneic)andtheantigenicdifferenceswillcauseanimmuneresponsetoallografts.TheantigensconcernedareoftenoftheMHCandarereferredtoasalloantigens.AntigenAutoantigen-Theantigensofanorganismsowncellsandcellproductsareselfantigenstotheimmunesystemofthatorganism.-Clonesofimmunecellsreactivewithselfantigensarenormallyeliminated.AntigenTypesofantigensHeterophilicAg(Forssmanantigen)-Across-reactingantigenthatappearsinwidelyrangingspeciessuchashumansandbacteria.Postinfectiousglomerulonephritis:groupAStreptococcusglomerularbasementmembraneAntigenForssmanantigen豚鼠免疫家兔肝、脾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