specificimmunitySpecificimmunityisestablishedonthebasisofthenon-specificimmunity.Itcanbeacquiredafterindividualwasstimulatedwithaantigen.第一頁(yè)，共38頁(yè)。IDefinitionandgeneralnature1.Antigen(Ag):5-1.Antigen(Ag)SubstancesthatcombinespecificallywithaBorTcell’santigen-bindingreceptorcantheninduceanimmuneresponse(positiveornegative)arecalledantigens.Positiveresponseresultsintheproductionofantibody/effectorTcells,andthatthenegativeresponsecausestheantigen-specificnon-reactivity，thatistolerance.第二頁(yè)，共38頁(yè)。Antigen(Ag)AntigenbindingcausescytotoxicTcellsMemoryTcellActivatedcytotoxicTcellAntigenbindingtriggersreleaseofantibodiesMemoryBcellActivatedBcellAntibodies第三頁(yè)，共38頁(yè)。2.Thebasicnaturesofantigen（1）immunogenicity（免疫原性)（2）immunoreactivity(反應(yīng)原性)orantigenicity(抗原性)Theantigenmoleculegenerallyposetwonatures,thatis第四頁(yè)，共38頁(yè)。(1)immunogenicityImmunogenicityistheabilitytoinduceahumoraland/orcellmediatedimmuneresponse,includinginduceproductionofantibodyandeffectorlymphocytes.ActivatedBcellantibodyActivatedCTL第五頁(yè)，共38頁(yè)。（2）immunoreactivityor

antigenicity抗原性Antigenicityistheabilitytocombinespecificallywiththefinalproductsoftheaboveresponses(i.e.,antibodyand/orcell-surfacereceptors).第六頁(yè)，共38頁(yè)。3、HaptenandvarrierHapten：somesmallmolecules,calledhaptens,areantigenicbutincapable,bythemselves,ofinducingaspedificimmuneresponse.Inotherwords,theylackimmunogenicitycarrier：smallorganicmoleculesthatareantigenicbutnotimmunogenic.Chemicalcouplingofhaptentoalargeprotein,calledacarrier,yieldsanimmunoginichapten-carrierconjugate.Animalsimmunizedwithsuchaconjugateproduceantibodiesspecificforthehaptendeterminant.Thesubstancethatcanmakethehaptenbeimmunogenic(iscapableofinducingimmuneresponse)arecalledcarrier.第七頁(yè)，共38頁(yè)。HAPTEN-CARRIERCONJUGATESA.Definition-Hapten-carrierconjugatesareimmunogenicmoleculestowhichhaptenshavebeencovalentlyattached.Theimmunogenicmoleculeiscalledthecarrier.B.Structure

-Structurallytheseconjugatesarecharacterizedbyhavingnativeantigenicdeterminantsofthecarrieraswellasnewdeterminantscreatedbythehapten(haptenicdeterminants)asillustratedintheFigure3.第八頁(yè)，共38頁(yè)。Hapten：

Haptenshavethepropertyofantigenicitybutnotimmunogenicity.Asubstancethatisnon-immunogenicbutwhichcanreactwiththeproductsofaspecificimmuneresponse.smallmoleculesimmuneresponse+carrierhapten+carrier=completeantigen第九頁(yè)，共38頁(yè)。II.FACTORSINFLUENCINGIMMUNOGENICITY1、chemicalandphysicalnatureofantigens（1）chemicalcharacteristic（2）moleculesize（3）complicatedchemicalstructure（4）conformationandaccessibility2、Host（1）foreignness（2）geneticcharacteristicsofthehost（3）Age,sex,andstateofhealth3、immunizedRoute第十頁(yè)，共38頁(yè)。1、chemicalandphysicalnatureofantigens（1）chemical

nature

glycoprotein,lipoprotein、polysaccharide、LPSDNA，chromosome、histoneintheactivatedlymphocyteAoto-antibodyforself-DNA,histoneAntinuclearantibody(ANA)Autoimmunodiseases第十一頁(yè)，共38頁(yè)。（2）moleculesize>10kD>100kD<10kDimmunogensStrongimmunogensPoorimmunogensThehigheristhemoleculeweightThemoreareantigenicdeterminantsThemorecomplexistheantigenicstructureNotbedegradatedeasilierStimulatingimmunecellcontinuouslyHighimmuneresponse第十二頁(yè)，共38頁(yè)。（3）復(fù)雜的化學(xué)結(jié)構(gòu)明膠分子（分子量>100kD）直鏈氨基酸加苯環(huán)氨基酸（2%酪氨酸）（免疫原性很弱）（免疫原性大大增強(qiáng)）第十三頁(yè)，共38頁(yè)。（4）分子構(gòu)象(conformation)的易接近性(accessibility)抗原性+++酪氨酸多聚丙氨酸谷氨酸多聚賴氨酸+++第十四頁(yè)，共38頁(yè)。（2）geneticcharacteristicsofthehost

Geneticcontrolofimmuneresponsiveness,largelyconfinedtogeneswithintheMHC.MHCgeneproducts,whichfunctiontopresentprocessedantigentoTcells,playacentralroleindeterminingthedegreeofimmuneresponsiveness.（3）Age,sex,andstateofhealth第十五頁(yè)，共38頁(yè)。IIISpecificityofantigen1.

Specificityofantigen

：Thecharacteristicthatantigenonlybindstheantibodyandsensitizedlymphocytespecifically,iscalledspecificityofantigen（Specificity）第十六頁(yè)，共38頁(yè)。Theeffectofcompositionandspatialstructureofchemicalgrouponthehapten-antibodyspecificityAnti-serumpositionresponsecompositionNH2SO3HantiNH2NH2-RNH2R-ROrtho-Meta-Para-R=SO3HR=ASSO3H2R=COOH+++++————++—+—serum第十七頁(yè)，共38頁(yè)。2、抗原決定基（antigenicdeterminant）：抗原分子中決定抗原特異性的特殊的化學(xué)基團(tuán)，它是TCR/BCR及抗體特異性結(jié)合的基本單位，又稱表位(epitope)。Antigenicdeterminantsorepitopes

aretheimmunologicallyactiveregionsofanimmunogenthatbindtoantigen-specificmembranereceptorsonlymphocytes(TCR/BCR)ortosecretedantibodies.第十八頁(yè)，共38頁(yè)。EpitopeorAntigenicDeterminantThatportionofanantigenthatcombineswiththeproductsofaspecificimmuneresponse.antigenantigenantigen第十九頁(yè)，共38頁(yè)。5、antigenicvalence(抗原的結(jié)合價(jià))antigenicvalenceisthenumbersofantigenicfunctionaldeterminantwhichbindtoantibodymolecules.Thehaptenisunivalence,andthenaturalantigenisgenerallymacromolecule,consistsofvariousandmultipleantigenicdeterminants,soitiscalledpolyvalentantigen,andcanbindmultipleantibodies.+第二十頁(yè)，共38頁(yè)。多價(jià)抗原第二十一頁(yè)，共38頁(yè)?？贵w：針對(duì)N端1~17氨基酸殘基T效應(yīng)細(xì)胞：針對(duì)C端18~29氨基酸殘基沒(méi)有發(fā)現(xiàn)一個(gè)表位同時(shí)被T細(xì)胞和B細(xì)胞識(shí)別。*B細(xì)胞表位是天然的，*位于分子的表面或轉(zhuǎn)折處*為構(gòu)象決定基或順序決定基*是抗原分子的三級(jí)結(jié)構(gòu)COOH123456789101112131415161718NH31920212223242526272829*T細(xì)胞表位是抗原提呈細(xì)胞加工提呈的抗原肽*呈線性排列第二十二頁(yè)，共38頁(yè)。**onsurfaceofmoleculeantigenantibodyCDR3epitopeBcellepitopeThesideontheantigenmoleculethatisrecognizedbyBCRandantibodyiscalledBcellepitope.**Theepitopeisthesmallestunitontheantigenthatcanbindstoantibody.**conformationaldeterminants（1）Bcellepitope第二十三頁(yè)，共38頁(yè)。（2）TcellepitopeThepeptidethatispresentedbyMHCmoleculeandrecognizedbyTCRiscalledTcellepitope.TCRMHCHIVpeptide第二十四頁(yè)，共38頁(yè)。TCRrecognizeMHC/antigenicpeptideTCRAntigenicpeptideMHC-IITcellAPC第二十五頁(yè)，共38頁(yè)。Ep1Ep2Ep3TCellepitopeAntigenicpeptidesrecognizedbyTcellformtrimolecularcomplexeswithaTCRandanMHCmoleculeirrelevanttoconformationofaproteinmoleculeMainlydependontheaminoacidsequenceofthepeptiderelevanttotheexpressionofMHCmoleculeofthehostirrelevanttoasitewherethepeptideisintheproteinmolecule第二十六頁(yè)，共38頁(yè)。ComparisonofepitopeofTandBcellTcellepitopeBcellepitopeReceptorTCRBCRMHCmoleculerequiredtodisplaynonerequiredprocessedantigencharacterlinerpeptidesnaturalpolypeptide,LPS,polysaccharide,organiccompound5~15aminoacids,5~7monosaccharideor5~7nucleotideEpitopetypelinerconformational,linersideanyonthesurfacesize8~12aminoacids(CD8+),12~17aminoacids(CD4+)第二十七頁(yè)，共38頁(yè)。Bcellepitope（hapten）naturalantigens(polyvalentantigen

–multi-determinants)Tcellepitope第二十八頁(yè)，共38頁(yè)。8、commonantigenandcross-reactionTherearemultiplyantigenicdeterminantsonthesurfaceofthenaturalantigens.EachBcelldeterminantinducesproductionofaspecificantibody.Therebyacomplicatedantigencaninduceproductionofmultiplyantibodies.Asameorsimilarantigenicdeterminantthatexistsbetweenthetwodifferentantigensiscalledcommonantigen.第二十九頁(yè)，共38頁(yè)。Thereactionthatantibodyreactswithsameorsimilarantigenicdeterminantbetweenthedifferentantigensiscalledcross-reaction.第三十頁(yè)，共38頁(yè)。IVtypeofantigen1.DependonwhetherneedtheThforproducingtheantibody**thymusdependentantigen,TD-Ag（胸腺依賴抗原）**thymusindependentantigen,TI-Ag（胸腺非依賴抗原）TDandTIarecompleteantigen(完全抗原)第三十一頁(yè)，共38頁(yè)。TIandTDantigen12CD40/CD40LBcellBcellThcellTI-antigenTDantigenCD412第三十二頁(yè)，共38頁(yè)。（4）hetorophilicantigen（異嗜性抗原）,or

Forssamantigen

HemolyticstreptococcusBCantigen乙型溶血性鏈球菌細(xì)胞壁C抗原MantigenM抗原Streptococcusinfection鏈球菌感染AcuteGlomerulonephritisLPSofE.coliO14Colonicmucosa結(jié)腸粘膜Ulcercolitis潰瘍性結(jié)腸炎GlycoproteinofCardiacvalve心瓣膜的糖蛋白heartmuscleRheumaticfever風(fēng)濕熱StreptococcusA

A族鏈球菌Glomerularbasementmembrane腎小球基底膜Thehetorophilicantigensarecommonantigen,whichareirrelevanttospeciesandexistinhuman,animal,plantandmicroorganism.急性腎小球腎炎第三十三頁(yè)，共38頁(yè)。WhentheimmunesystemencountersaconventionalT-dependentantigen,onlyasmallfraction(1in104-105)oftheTcellpopulationisabletorecognizetheantigenandbecomeactivated(monoclonal/oligoclonalresponse).However,therearesomeantigenswhichpolyclonallyactivatealargefractionoftheTcells(upto25%).Theseantigensarecalledsuperantigens.2、超抗原(SUPERANTIGENS)第三十四頁(yè)，共38頁(yè)。超抗原

TCRVb抗原肽MHC-IIaT細(xì)胞APC超抗原（superantigens,SAg）能同時(shí)與MHC分子及TCR多肽結(jié)合，從而激活多克隆T細(xì)胞的蛋白質(zhì)大分子。超抗原能與MHC-II分子及TCRb鏈結(jié)合，從而造成T細(xì)胞的非特