INSTITUTEFORIMMUNOBIOLOGY抗原/免疫原及其識別(Antigen/Immunogenanditsrecognition)DepartmentofImmunologyShanghaiMedicalCollegeofFudanUniversity洪曉iaowuhong@獲得性免疫(AcquiredImmunity)適應性免疫(AdaptiveImmunity)特異性免疫(SpecificImmunity)固有免疫(InnateImmunity)先天免疫(NativeImmunity)非特異性免疫(NonspecificImmunity)種系發(fā)育，進化形成生來具備，應答迅速非特異性抗感染免疫也參與特異性免疫固有免疫應答和適應性免疫應答的比較固有免疫應答 適應性免疫應答長期進化中逐漸形成 抗原激發(fā)種系共有，可遺傳 個體特有，不可遺傳無免疫記憶、作用時間短 有免疫記憶、作用時間長粘膜和上皮細胞、吞噬細胞、NKT細胞、B細胞、APC gdT細胞、B－1B細胞不針對特定抗原（反應廣泛） 針對特定抗原（反應特異性）作用迅速、范圍廣泛 抗原識別、增殖分化、效應階段

免疫（Immunity）固有免疫（Innateimmunity）適應性免疫（Adaptiveimmunity）抗原/免疫原的概念免疫原（Immunogen）--啟動免疫應答的物質(zhì)抗原（antigen,Ag）--啟動適應性免疫應答的物質(zhì)固有免疫原（Innagen，Ing）--啟動固有免疫應答的物質(zhì)

固有免疫識別的效應 產(chǎn)生活性氧、活性氮、抗菌肽 細胞因子、粘附分子、急性期蛋白 共刺激分子（B7.1、B7.2)

PAMP、DAMP啟動、激發(fā)以炎癥反應為主的免疫應答，清除病原體和凋亡細胞固有免疫識別的效應Ag啟動、激發(fā)以特異性CTL和Ab為主的免疫應答，清除病原體和靶細胞產(chǎn)生致敏的淋巴T細胞和Ab適應性免疫識別的效應適應性免疫識別的效應

ImmunogenInnagen(INg)/InnateMolecularPattern(IMP)Antigen(Ag)PAMPDAMPOthers?ImmunogenicityReactigenicity熊思東.道亦道,非故道----試論固有免疫中的抗原和免疫原的定義.現(xiàn)代免疫學,2007,27(6):441-443抗原/免疫原的概念抗原的特性免疫原性（immunogenicity）抗原性（antigenicity）AgTBT漿細胞致敏T細胞抗體免疫原性(immunogenecity)

指抗原分子能夠刺激機體產(chǎn)生免疫應答(產(chǎn)生特異性抗體及免疫效應細胞)的性質(zhì)。AgTBT漿細胞致敏T細胞抗原性

指抗原分子與免疫應答產(chǎn)物(抗體或免疫效應細胞)發(fā)生特異性結(jié)合的性質(zhì)?？乖?antigenicity)antigenicityimmuogenicityTTTAg免疫原的特點固有免疫原抗原不限于特定類別的成分或單一分子啟動、誘導固有免疫應答免疫原性、免疫反應性分離免疫原性、免疫反應性一致啟動、誘導適應性免疫應答以表位為識別基礎(chǔ)就免疫應答始動因素而言

異物性是抗原免疫原性的本質(zhì)。非己就是異物，抗原來源與宿主的關(guān)系越遠，異物越強,免疫原性也越強?？乖漠愇镄钥乖禺愋愿拍?-指某一抗原分子只能誘導相應淋巴細胞發(fā)生免疫應答的專一性，以及只能與相應抗體或效應細胞特異性結(jié)合的專一性。意義--是免疫學診斷與防治的理論依據(jù)

(1)兩對半：檢測HBV(2)接種牛痘：消滅天花決定抗原特異性的物質(zhì)基礎(chǔ)表位T細胞抗原受體及其識別抗原的特點MHC與peptides

只識別表達于細胞表面非己MHC或與自身MHC分子結(jié)合成復合物的多肽

只識別氨基酸一級序列的多肽線性決定簇TCR識別抗原肽受到自身MHC的限制——

CD4+T只識別與MHC-II分子結(jié)合的肽段

CD8+T只識別與MHC-I分子結(jié)合的肽段只有A圖中TCR可識別APC所遞呈的抗原，形成TCR-抗原肽三分子復合體,產(chǎn)生TH細胞活化的第一信號Primaryactivationofna?veTcellsrequirestwoindependentsignalssignal1:specificbutweakinteractionbetweenMHC:peptidecomplexandTCR/CD4orTCR/CD8signal2(co-stimulator),interactionsbetween:B7andCD28(required)adhesionmolecules(optional,increasecontact)O=C-CH2-CH2…AntigenCH2-OHCH2-CH2-NH3+C-CH2-CH2=O-OCH2CH2-CH2CH2CH2-CH2CH2CH2-CH2-CH2CH2CH2-CH2CH2CH2-C=O-O+H3N-CH2IonicbondvanderWaalsinteractionsHydrophobicinteractionsHydrogenbondIonicbondAntibodyRestingBcellCrosslinkedBcellAntigenB-cellmembraneIg-α/βCytoplasmITAMFynBlkLckITAMsequenceSrcSykKinases固有免疫的分子識別一般概念PRRs－PAMPs天然免疫分子識別的機制一般概念固有免疫機制存在對“異己”的分子識別分子識別可區(qū)分“有害”和“無害”物質(zhì)分子識別依賴多種受體和細胞膜分子分子識別并非針對某一特點的抗原

bacteriumsig1(stimulation)1959,originalSNSmodel:lymphocytesareactivatedbyrecognitionofforeignthings.BcellSirFMBurnet(1899-1985)

CohnM,MitchisonNA,PaulWEetal.Reflectionsontheclonal-selectiontheory.NatRevImmunol.2007,7:823-30.ClonalselectionTheSelf-NonselfModelBurnet’soriginalmodeleachlymphocyteexpresssmutiplecopiesofasinglesurfacereceptorspecificforaforeignentity.signalingthroughthissurfacereceptorinitiatestheimmuneresponse.theself-reactivelymphocytesaredeletedearlyinlife1969Bretscher&CohnBcellsdiewhentheyseeantigen(signalone)unlessrescuedbyhelp(signaltwo)sig1BcellTcellsig1(stimulation)TwosignalmodelCostimulationSig2(co-stimulation)1975Lafferty&CunninghamThelpercellsdiewhentheyseeantigenunlessrescuedbyco-stimulation(signaltwo)fromAPCs.bacteriumPRRs1989JanewayAPCsdonotco-stimulateunlessactivatedviaPRRs(receptorsforevolutionarilydistantinfectiousnon-self)PRRs-PAMPsC.A.Janeway,Jr.,M.D.TheInfectious-NonselfModel(1943-2003)APCsareactivatedbydanger/alarmsignalsfrominjuredcells,suchasthoseexposedtopathogens,toxins,mechanicaldamage,andsoforthTheDangermodelPollyMatzinger1994PollyMatzinger

APCsareactivatedbyendogenouscellularalarmsignalsfromdistressedorinjuredcellsDistressedcellNormalcellSteinmanRM,CohnZA.Identificationofanovelcelltypeinperipherallymphoidorgansofmice.I.Morphology,quantitation,tissuedistribution.

JExpMed.1973May1;137(5):1142-62.SteinmanRM,CohnZA.Identificationofanovelcelltypeinperipherallymphoidorgansofmice.II.Functionalpropertiesinvitro.JExpMed.1974Feb1;139(2):380-97.SteinmanRM,LustigDS,CohnZA.Identificationofanovelcelltypeinperipherallymphoidorgansofmice.3.Functionalpropertiesinvivo.JExpMed.1974Jun1;139(6):1431-45.SteinmanRM,AdamsJC,CohnZA.Identificationofanovelcelltypeinperipherallymphoidorgansofmice.IV.Identificationanddistributioninmousespleen.JExpMed.1975Apr1;141(4):804-20.SteinmanRM,KaplanG,WitmerMD,CohnZA.Identificationofanovelcelltypeinperipherallymphoidorgansofmice.V.Purificationofspleendendriticcells,newsurfacemarkers,andmaintenanceinvitro.JExpMed.1979Jan1;149(1):1-16.DC的發(fā)現(xiàn)/research/abstract.php?id=150RalphMSteinman.Dendriticcells:versatilecontrollersoftheimmunesystem.NatureMedicine,2007,13,1155-1159steinma@

RalphMSteinmanCohnZAandRalphMSteinmanCohnZAandRalphMSteinmanMichelNussenzweig,KayoInabaandWesleyvanVoorhis/files/0801profile.pdf固有免疫識別受體及其配體模式識別受體及其配體自身抗原識別受體及其配體

模式識別受體（Patternrecognitionreceptors,PRRs）分泌型受體MBLLBP

sCD14

細胞表面受體CD14TLR(Toll-likereceptors，TLRs)PGRP（昆蟲細胞）巨噬細胞甘露糖受體巨噬細胞清道夫受體細胞內(nèi)受體NODs（nucleotide-bindingoligomerizationdomain，NODs）Mannan-bindinglectinformsacomplexwithserineprote