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1、Antigensandadaptiveimmuneresponses 抗原与获得性免疫应答 specificimmunity Specificimmunityisestablishedonthebasisofthenon specificimmunity Itcanbeacquiredafterindividualwasstimulatedwithaantigen IDefinitionandgeneralnature 1 Antigen Ag 5 1 Antigen Ag SubstancesthatcombinespecificallywithaBorTcell santigen bind
2、ingreceptorcantheninduceanimmuneresponse positiveornegative arecalledantigens Positiveresponseresultsintheproductionofantibody effectorTcells andthatthenegativeresponsecausestheantigen specificnon reactivity thatistolerance Antigen Ag AntigenbindingcausescytotoxicTcells MemoryTcell Activatedcytotoxi
3、cTcell 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 orcellmed
4、iatedimmuneresponse includinginduceproductionofantibodyandeffectorlymphocytes ActivatedBcell antibody ActivatedCTL 2 immunoreactivityorantigenicity抗原性 Antigenicityistheabilitytocombinespecificallywiththefinalproductsoftheaboveresponses i e antibodyand orcell surfacereceptors 3 Haptenandvarrier Hapte
5、n somesmallmolecules calledhaptens areantigenicbutincapable bythemselves ofinducingaspedificimmuneresponse Inotherwords theylackimmunogenicity carrier smallorganicmoleculesthatareantigenicbutnotimmunogenic Chemicalcouplingofhaptentoalargeprotein calledacarrier yieldsanimmunoginichapten carrierconjug
6、ate Animalsimmunizedwithsuchaconjugateproduceantibodiesspecificforthehaptendeterminant Thesubstancethatcanmakethehaptenbeimmunogenic iscapableofinducingimmuneresponse arecalledcarrier HAPTEN CARRIERCONJUGATES A Definition Hapten carrierconjugatesareimmunogenicmoleculestowhichhaptenshavebeencovalentl
7、yattached Theimmunogenicmoleculeiscalledthecarrier B Structure Structurallytheseconjugatesarecharacterizedbyhavingnativeantigenicdeterminantsofthecarrieraswellasnewdeterminantscreatedbythehapten haptenicdeterminants asillustratedintheFigure3 Hapten Haptenshavethepropertyofantigenicitybutnotimmunogen
8、icity Asubstancethatisnon immunogenicbutwhichcanreactwiththeproductsofaspecificimmuneresponse smallmolecules immuneresponse carrier hapten carrier completeantigen II FACTORSINFLUENCINGIMMUNOGENICITY 1 chemicalandphysicalnatureofantigens 1 chemicalcharacteristic 2 moleculesize 3 complicatedchemicalst
9、ructure 4 conformationandaccessibility2 Host 1 foreignness 2 geneticcharacteristicsofthehost 3 Age sex andstateofhealth3 immunizedRoute 1 chemicalandphysicalnatureofantigens 1 chemicalnatureglycoprotein lipoprotein polysaccharide LPSDNA chromosome histoneintheactivatedlymphocyte Aoto antibodyforself
10、 DNA histone Antinuclearantibody ANA Autoimmunodiseases 2 moleculesize 10kD 100kD 10kD immunogens Strongimmunogens Poorimmunogens Thehigheristhemoleculeweight ThemoreareantigenicdeterminantsThemorecomplexistheantigenicstructure Notbedegradatedeasilier Stimulatingimmunecellcontinuously Highimmuneresp
11、onse 3 复杂的化学结构 明胶分子 分子量 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 playac
12、entralroleindeterminingthedegreeofimmuneresponsiveness 3 Age sex andstateofhealth IIISpecificityofantigen 1 Specificityofantigen Thecharacteristicthatantigenonlybindstheantibodyandsensitizedlymphocytespecifically iscalledspecificityofantigen Specificity Theeffectofcompositionandspatialstructureofche
13、micalgrouponthehapten 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 Antigenicdeterminantsorepitopesaretheimmunologicallya
14、ctiveregionsofanimmunogenthatbindtoantigen specificmembranereceptorsonlymphocytes TCR BCR ortosecretedantibodies EpitopeorAntigenicDeterminant Thatportionofanantigenthatcombineswiththeproductsofaspecificimmuneresponse antigen antigen antigen 5 antigenicvalence 抗原的结合价 antigenicvalenceisthenumbersofan
15、tigenicfunctionaldeterminantwhichbindtoantibodymolecules 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
16、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 irre