免疫学课件Antigen.ppt

Antigen Pathogen associatedmoleculepattern病原体相关模式分子 Foot and mouthdiseasevirus Avianinfluenzavirus MoleculepatternofGramnegativebacteria革兰氏阴性细菌表面模式分子 Toll likereceptor TLR WhyisanDNAmolecule Or RNAmoleculecalledantigen Innateimmunesystemrecognizes dangersignals 2 1ConceptofAntigen Antigensaresubstancesthatinduceaspecificimmuneresponseandsubsequentlyreactwiththeproductsofaspecificimmuneresponse 抗原是能够刺激机体免疫系统产生特异性免疫应答 并能与相应免疫应答产物 抗体或致敏淋巴细胞 在体内外发生特异性结合的物质 也叫免疫原 immunogen Anantigenisamoleculethatstimulatesanimmuneresponse Theword antigen originatedfromthenotionthattheycanstimulateantibodygeneration Wenowknowthattheimmunesystemdoesnotonlyconsistofantibodies Themoderndefinitionencompassesallsubstancesthatcanberecognizedbytheadaptiveimmunesystem i e Tcell Bcell Tolerogen Anantigenthatinvokesaspecificimmunenon responsivenessduetoitsmolecularform Ifitsmolecularformischanged atolerogencanbecomeanimmunogen Allergen Anallergenisasubstancethatcausestheallergicreaction The detrimental reactionmayresultafterexposureviaingestion inhalation injectionorcontactwithskin Antigenscanbeclassifiedinorderoftheirorigins ExogenousantigensExogenousantigensareantigensthathaveenteredthebodyfromtheoutside forexamplebyinhalation ingestion orinjection Byendocytosisorphagocytosis theseantigensaretakenintotheantigen presentingcells APCs andprocessedintofragments EndogenousantigensEndogenousantigensareantigensthathavebeengeneratedwithinthecell asaresultofnormalcellmetabolism orbecauseofviralorintracellularbacterialinfection AutoantigensAnautoantigenisusuallyanormalproteinorcomplexofproteins andsometimesDNAorRNA thatisrecognizedbytheimmunesystemofanimalssufferingfromaspecificautoimmunedisease Theseantigensshouldundernormalconditionsnotbethetargetoftheimmunesystem butduetomainlygeneticandenvironmentalfactorsthenormalimmunologicaltoleranceforsuchanantigenhasbeenlostintheseanimals TumorantigensTumorantigensarethoseantigensthatarepresentedbytheMHCImoleculesonthesurfaceoftumorcells Theseantigenscansometimesbepresentedonlybytumorcellsandneverbythenormalcells Inthiscase theyarecalledtumor specificantigens TSAs andtypicallyresultfromatumorspecificmutation 2 2CharacteristicsofAntigen 1 Immunogenicity免疫原性Thecapacitytostimulatetheproductionofantibodiesorcell mediatedimmuneresponses 1 2 2 Antigenicity抗原性 反应原性 Theabilitytobindantibody 3 Completeantigen完全抗原Antigenhasbothimmunogenicityandantigenicity 4 Incompleteantigen alsoknownashapten不完全抗原 或半抗原Antigenhasonlyantigenicity Efficacyofcarrier OVA 鸡 卵白素DNP 二硝基苯BSA 牛血清白蛋白 Incompleteantigenshaveantigenicdeterminants butcannotinduceimmuneresponsesbecausetheylackoneormoreoftheimportantattributesneededforthisfunction oneexampleofanincompleteantigenisahapten whichisanartificialmonovalentepitope 2 3Propertiesofantigen Foreignnessisessentialtoimmunogenicitybecauseself responsivecellsareeliminatedduringlymphocyteontogeny leavingonlycellsthatrespondtonon self so called foreign epitopes 异物性Specificity特异性Highmolecularweight MoleculeofHemoglobin 2 4Antigenicepitopes Epitopes or Antigenicdeterminants Aretheportionsofantigenmoleculesthatphysicallyinteractwithparatopes combiningsites ofimmuneresponsemoleculesandthereforeactually determine antigenspecificity ThreedimensionalstructureofM tuberculosisantigen85B 2 4 1Antigenicepitopes 2 4 2TypesofEpitopes 1 Linearepitopes continuousandfoundinpolysaccharidesaswellasinbothnative nondenatured anddenaturedproteins especiallyfibrillarproteins specificitydependsuponprimarysequence typicalsizeis5 6subunitsinlength 2 Conformationalepitopes Discontinuous involvemultiplesubunits oftenlocatedfarapartintheprimarysequenceoftheantigenmolecule andarethusfoundonlyinnative globular proteins Specificitydependsuponconformation orthree dimensionalshape whichisacombinationoftertiaryandquaternarystructuresupportedbyprimaryandsecondarystructures ofcourse Typicalsizeishardtopinpoint butsequencesofupto16aminoacidsincertainproteinantigenshavebeenshowntointeractwiththeircomplementaryparatope Twodifferentepitopes Bcellepitope aportionofantigenmoleculethatisrecognizedbyBcellreceptors BCR Tcellepitope theregionofantigenmoleculesthatarerecognizedbyTcellreceptors TCR TcellepitopeandBcellepitope 2 5ClassificationofAntigens Thymus dependentantigen TD Ag 胸腺依赖抗原Thymus independentantigen TI Ag 胸腺非依赖抗原 2 6Superantigen超抗原 MoleculesthatarepotentTlymphocytemitogensandsimultaneouslybindtoMHC IImolecules Theyareoftenassociatedwithstaphylococcalproductsandareinvolvedinenterotoxemiaandtoxicshocksyndromeinhumans Superantigens SAgs aresecretedproteins exotoxins thatexhibithighlypotentlymphocyte transforming mitogenic activitydirectedtowardsTlymphocytes SuperantigensarenotprocessedandinteractwiththeMHCmoleculeoutsideofthepeptide bindinggroove SuperantigensonlybindtoV segmentofTCR TCR ConventionalAg Comparedtoanormalantigen inducedT cellresponsewhere0 001 0 0001 ofthebody sT cellsareactivated SAgsarecapableofactivatingupto20 ofthebody sT cells ThiscausesamassiveimmuneresponsethatisnotspecifictoanyparticularepitopeontheSAg Superantigens Monoclonal OligoclonalTcellresponse1 104 1 105 2 7Mitogen丝裂原 Anagentthatinducesmitosis HeremeanstoactivateTcellsand orBcellswithouthelpfromAPCs Lectin forexample concanavalinA ConA LPS lipopolysaccharide StaphylococcalproteinA SPA 2 8Adjuvant Adjuvant TheLatin adjuvans meanstohelp particularlytoreachagoal Anadjuvantisasubstancethathelpsandenhancesthepharmacologicaleffectofadrugorincreasestheabilityofanantigentostimulatetheimmunesystem ClassificationofAdjuvant Freund sadjuvant CompleteFreund sadjuvant CFA IncompleteFreund sadjuvant IFA LiposomeInorganiccompoundCytokineBiodegradablenanoparticles Mechanismsofadjuvants Prolongedpersistenceofimmunogenmoleculesatthesiteofinjection Enhancementofco stimulatorysignals Inductionofgran