抗原与获得性免疫应答Englishversion.ppt

Antigensandadaptiveimmuneresponses,抗原与获得性免疫应答,specificimmunity,Specificimmunityisestablishedonthebasisofthenon-specificimmunity.Itcanbeacquiredafterindividualwasstimulatedwithaantigen.,IDefinitionandgeneralnature,1.Antigen(Ag):,5-1.Antigen(Ag),SubstancesthatcombinespecificallywithaBorTcellsantigen-bindingreceptorcantheninduceanimmuneresponse(positiveornegative)arecalledantigens.Positiveresponseresultsintheproductionofantibody/effectorTcells,andthatthenegativeresponsecausestheantigen-specificnon-reactivity，thatistolerance.,Antigen(Ag),AntigenbindingcausescytotoxicTcells,MemoryTcell,ActivatedcytotoxicTcell,Antigenbindingtriggersreleaseofantibodies,MemoryBcell,ActivatedBcell,Antibodies,2.Thebasicnaturesofantigen,（1）immunogenicity（免疫原性)（2）immunoreactivity(反应原性)orantigenicity(抗原性),Theantigenmoleculegenerallyposetwonatures,thatis,(1)immunogenicity,Immunogenicityistheabilitytoinduceahumoraland/orcellmediatedimmuneresponse,includinginduceproductionofantibodyandeffectorlymphocytes.,ActivatedBcell,antibody,ActivatedCTL,（2）immunoreactivityorantigenicity抗原性,Antigenicityistheabilitytocombinespecificallywiththefinalproductsoftheaboveresponses(i.e.,antibodyand/orcell-surfacereceptors).,3、Haptenandvarrier,Hapten：somesmallmolecules,calledhaptens,areantigenicbutincapable,bythemselves,ofinducingaspedificimmuneresponse.Inotherwords,theylackimmunogenicity,carrier：smallorganicmoleculesthatareantigenicbutnotimmunogenic.Chemicalcouplingofhaptentoalargeprotein,calledacarrier,yieldsanimmunoginichapten-carrierconjugate.Animalsimmunizedwithsuchaconjugateproduceantibodiesspecificforthehaptendeterminant.Thesubstancethatcanmakethehaptenbeimmunogenic(iscapableofinducingimmuneresponse)arecalledcarrier.,HAPTEN-CARRIERCONJUGATES,A.Definition-Hapten-carrierconjugatesareimmunogenicmoleculestowhichhaptenshavebeencovalentlyattached.Theimmunogenicmoleculeiscalledthecarrier.,B.Structure-Structurallytheseconjugatesarecharacterizedbyhavingnativeantigenicdeterminantsofthecarrieraswellasnewdeterminantscreatedbythehapten(haptenicdeterminants)asillustratedintheFigure3.,Hapten：,Haptenshavethepropertyofantigenicitybutnotimmunogenicity.,Asubstancethatisnon-immunogenicbutwhichcanreactwiththeproductsofaspecificimmuneresponse.,smallmolecules,immuneresponse,+,carrier,hapten+carrier=completeantigen,II.FACTORSINFLUENCINGIMMUNOGENICITY,1、chemicalandphysicalnatureofantigens（1）chemicalcharacteristic（2）moleculesize（3）complicatedchemicalstructure（4）conformationandaccessibility2、Host（1）foreignness（2）geneticcharacteristicsofthehost（3）Age,sex,andstateofhealth3、immunizedRoute,1、chemicalandphysicalnatureofantigens,（1）chemicalnatureglycoprotein,lipoprotein、polysaccharide、LPSDNA，chromosome、histoneintheactivatedlymphocyte,Aoto-antibodyforself-DNA,histone,Antinuclearantibody(ANA),Autoimmunodiseases,（2）moleculesize,10kD,100kD,100kD）,直链氨基酸,加苯环氨基酸（2%酪氨酸）,（免疫原性很弱）,（免疫原性大大增强）,（4）分子构象(conformation)的易接近性(accessibility),抗原性+,酪氨酸多聚丙氨酸谷氨酸多聚赖氨酸,+,（2）geneticcharacteristicsofthehostGeneticcontrolofimmuneresponsiveness,largelyconfinedtogeneswithintheMHC.MHCgeneproducts,whichfunctiontopresentprocessedantigentoTcells,playacentralroleindeterminingthedegreeofimmuneresponsiveness.,（3）Age,sex,andstateofhealth,IIISpecificityofantigen,1.Specificityofantigen：Thecharacteristicthatantigenonlybindstheantibodyandsensitizedlymphocytespecifically,iscalledspecificityofantigen（Specificity）,Theeffectofcompositionandspatialstructureofchemicalgrouponthehapten-antibodyspecificity,Anti-serum,position,response,composition,NH2,SO3H,anti,NH2,NH2,-R,NH2,R,-R,Ortho-,Meta-,Para-,R=SO3H,R=ASSO3H2,R=COOH,+,+,+,serum,2、抗原决定基（antigenicdeterminant）：抗原分子中决定抗原特异性的特殊的化学基团，它是TCR/BCR及抗体特异性结合的基本单位，又称表位(epitope)。,Antigenicdeterminantsorepitopesaretheimmunologicallyactiveregionsofanimmunogenthatbindtoantigen-specificmembranereceptorsonlymphocytes(TCR/BCR)ortosecretedantibodies.,EpitopeorAntigenicDeterminant,Thatportionofanantigenthatcombineswiththeproductsofaspecificimmuneresponse.,antigen,antigen,antigen,5、antigenicvalence(抗原的结合价),antigenicvalenceisthenumbersofantigenicfunctionaldeterminantwhichbindtoantibodymolecules.Thehaptenisunivalence,andthenaturalantigenisgenerallymacromolecule,consistsofvariousandmultipleantigenicdeterminants,soitiscalledpolyvalentantigen,andcanbindmultipleantibodies.,多价抗原,没有发现一个表位同时被T细胞和B细胞识别。,*onsurfaceofmolecule,antigen,antibodyCDR3,epitope,Bcellepitope,ThesideontheantigenmoleculethatisrecognizedbyBCRandantibodyiscalledBcellepitope.,*Theepitopeisthesmallestunitontheantigenthatcanbindstoantibody.,*conformationaldeterminants,（1）Bcellepitope,（2）Tcellepitope,ThepeptidethatispresentedbyMHCmoleculeandrecognizedbyTCRiscalledTcellepitope.,TCR,MHC,HIVpeptide,TCRrecognizeMHC/antigenicpeptide,TCR,Antigenicpeptide,MHC-II,Tcell,APC,Ep1,Ep2,Ep3,TCellepitope,AntigenicpeptidesrecognizedbyTcellformtrimolecularcomplexeswithaTCRandanMHCmolecule,irrelevanttoconformationofaproteinmolecule,Mainlydependontheaminoacidsequenceofthepeptide,relevanttotheexpressionofMHCmoleculeofthehost,irrelevanttoasitewherethepeptideisintheproteinmolecule,ComparisonofepitopeofTandBcell,TcellepitopeBcellepitope,ReceptorTCRBCR,MHCmoleculerequiredtodisplaynonerequiredprocessedantigen,characterlinerpeptidesnaturalpolypeptide,LPS,polysaccharide,organiccompound,515aminoacids,57monosaccharideor57nucleotide,Epitopetypelinerconformational,liner,sideanyonthesurface,size,812aminoacids(CD8+),1217aminoacids(CD4+),Bcellepitope（hapten）,naturalantigens(polyvalentantigenmulti-determinants),Tcellepitope,8、commonantigenandcross-reaction,Therearemultiplyantigenicdeterminantsonthesurfaceofthenaturalantigens.EachBcelldeterminantinducesproductionofaspecificantibody.Therebyacomplicatedantigencaninduceproductionofmultiplyantibodies.Asameorsimilarantigenicdeterminantthatexistsbetweenthetwodifferentantigensiscalledcommonantigen.,Thereactionthatantibodyreactswithsameorsimilarantigenicdeterminantbetweenthedifferentantigensiscalledcross-reaction.,IVtypeofantigen,1.DependonwhetherneedtheThforproducingtheantibody,*thymusdependentantigen,TD-Ag（胸腺依赖抗原）,*thymusindependentantigen,TI-Ag（胸腺非依赖抗原）,TDandTIarecompleteantigen(完全抗原),TIandTDantigen,1,2,CD40/CD40L,Bcell,Bcell,Thcell,TI-antigen,TDantigen,CD4,（4）hetorophilicantigen（异嗜性抗原）,orForssamantigen,HemolyticstreptococcusBCantigen乙型溶血性链球菌细胞壁C抗原MantigenM抗原,Streptococcusinfection链球菌感染,AcuteGlomerulonephritis,LPSofE.coliO14,Colonicmucosa结肠粘膜,Ulcercolitis溃疡性结肠炎,GlycoproteinofCardiacvalve心瓣膜的糖蛋白heartmuscle,Rheumaticfever风湿热,StreptococcusAA族链球菌,Glomerularbasementmembrane肾小球基底膜,Thehetorophilicantigensarecommonantigen,whichareirrelevanttospeciesandexistinhuman,animal,plantandmicroorganism.,急性肾小球肾炎,WhentheimmunesystemencountersaconventionalT-dependentantigen,onlyasmallfraction(1in104-105)oftheTcellpopulationisabletorecognizetheantigenandbecomeactivated(monoclonal/oligoclonalresponse).However,therea