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1、Chapter4Antigen1.DefinitionofantigenAntigen:anysubstancesthatcaninduceaspecificimmuneresponseandspecificallybindwithimmuneresponseproductsandlymphocytesreceptors(BCRandTCR)invitroorinvivo.Antigen.Tolerogen.AllergenSectionIPropertiesofAntigen AgT TB BT TPlasma cellPlasma cellEffector T cellEffector T
2、 cellImmunoreactivityImmunoreactivityImmunogenicity2.TwopropertiesofAg1)Immunogenicity:theabilityofantigenwhichcanstimulatethebodytoevokeaspecificimmuneresponse2)Immunoreactivity:theabilityofantigenwhichcancombinewithcorrespondingAborsensitizedTymphocyte.lImmunogen(Completeantigen):Molecules that ca
3、n stimulate immuneresponsearecalledimmunogens.lHapten:OnlypossessimmunoreactivityCarrier:EnhancetheimmunogenicityofhaptenHapten+carriercompleteantigen3.Structureofantigen4.SpecificityandcrossreactionSpecificityExistinbothimmunogenecityandimmunoreactivityThebasisofimmunologicdiagnosisandimmunologicth
4、erapyAntigenicdeterminants(epitope)Theportionofantigenmoleculeswhichcanspecificallybindwithantibodyorantigenicreceptoroflymphocytes.Proteinantigen-5-15aminoacidresiduesPolysaccharideantigen-5-7polysaccharideresidues Antigenicvalence Totalnumberofdeterminantswhichcanbeboundbyantibodyorantigenicrecept
5、oroflymphocytesiscalledantigenicvalence.Mostnaturalantigensarepolyvalenceantigen.AntigenicdeterminantsClassificationofantigenicdeterminant(1)AccordingtothestructureofAgdeterminantsConformationaldeterminantsSequential(orlinear)determinantsConformationaldeterminantsConformationaldeterminants are forme
6、d by amino acid residues that arent in a sequence but become spatially juxtaposed in the folded protein. - They are normally exist on the surface of antigen molecules. -They are recognized by B cells or antibody. Sequential(orlinear)determinantsEpitopesformedbyseveraladjacentaminoacidresiduesarecall
7、edlineardeterminants.MostofthemexistinsidetheAg,someofthemexistonthesurfaceofAg.TheyaremainlyrecognizedbyTcells,butsome(onthesurface)alsocanberecognizedbyBcells.(2)AccordingtotypesofcellsrecognizingantigenicdeterminantsTcelldeterminants(Tcellepitopes)Bcelldeterminants(Bcellepitopes)conformationallin
8、earDifferencebetweenTcellepitopeandBcellepitope TcellepitopeBcellepitopeReceptorTCRBCRNatureshortpeptideproteins,polysaccharidesSize8-17aminoacidresidues5-15aminoacidresiduesor5-7monosaccharidesTypeslinearepitopeconformationalepitopeorlinearepitopePositionanypositioninantigenthesurfaceofantigen 5.Co
9、mmonantigenandcrossreactionCommonantigen The same or similar determinants amongvariousantigensarecalledcommonantigen.CrossreactionTheantibodiesinducedbyoneantigencanreact with another antigen because ofpresence of common determinant betweentwoantigens. A1232BAnti-AAnti-2Anti-1Anti-2Anti-3Anti-BCross
10、reactionMechanismofcrossreaction-common Ag determinants -similar structure of Ag determinantsEffect Antiserum against one kind of Ag can also react with another Ag and cause a cross reaction . Inclinic,existenceofcrossreactionmayleadtowrongdiagnosis.I.Factorsrelatedtoantigens1）Foreignness“Non-self ”
11、substances: means substances which never contactwith embryonic lymphocytes according to Burnets selectiontheory. Xeno-substances (Various pathogens and their products, xeno-protein, etc.) Allo-substances (ABO blood type, HLA, et al)Selfcomponents-degeneration-releaseofsequesterantigen-forbiddenclone
12、rejuvenateSectionIIFactorsthatinfluenceimmunogenicityofAg2.Certainphysicalandchemicalproperties1)MolecularweightReasonablelargemolecule(10.0kd)stableandcomplexmore surface structures for lymphocytes torecognize2)chemicalcompositionandstructureProteinsPolysaccharidesNucleicAcidsLipidsaromaticring-mor
13、eimmunogenicityringlinear3)physicalnaturePolymerMonomerParticulateSolubleDenaturedNativeThechemicalcomponent,arrangementandconformationaffectthespecificityofantigenII.Factorsrelatedtohost1.Inheritance(Species,Individual)2.Age,sexandhealthyconditionIIIMethodsofimmunity1.Dosageofantigen,timesofinjecti
14、on2.Ways(subcutaneousintravenousoral)3.AdjuvantCertainsubstancewhichcanenhancetheimmuneresponseorchangethetypeofimmuneresponse.ClassificationbasedonthedependenceofTcellsClassificationbasedonphylogeneticrelationshipBasedonthenatureandsourceofantigenSectionIII.ClassificationofAg1.Classificationbasedon
15、thedependenceofTcells1)TD-Ag(thymusdependentAg)2)TI-Ag(thymusindependentAg)1)TD-Ag(thymusdependentAg).MostofTD-Agareprotein.Manykindsofdeterminant,eachisless.StimulateBcelltoproduce:IgG,IgM,IgA.CapableofinducingCMI.Immunememory2)TI-Ag(thymusindependentAg)lMostTI-AgarepolysaccharidelTherearemanysame,
16、repeatdeterminantslOnlyinduceBcelltoproduceIgMlCannotinduceCMIlNoimmunememoryXenogenicantigenallogenicantigenAutoantigenHeterophilicantigenTumorantigenAllogenicantigenXenogenicantigenautoantigen2.ClassificationbasedonphylogeneticrelationshipHeterogenousAg(xenogenicantigen)1)pathogensandtheirproducts
17、MicrobialAg:Surfaceantigen-“Vi”AgSomaticAg-“O”AgFlagellarAg-“H”AgPillusAg2)ExotoxinandtoxoidExotoxin.ProducedbyG+bacteria.StrongimmunogenicityandpathogenicityToxoidUnder certain conditions, exotoxin lose its toxicitywithoutaffectingitsimmunogenicity,thentheexotoxinbecomestoxoid. Tetanus toxoid3)Anim
18、alimmuneseraAnimalserumcontainsAbsafterbeingimmunizedbysomeAg.Antibodyactivation:bindtoantigenImmunogenicity:hypersensitivityTAT:Tetanusanti-toxin4)Antigenandvaccine.Vaccinenon-toxicantigenpreparation.ItisveryimportantininducingamemoryresponseAllogenicantigen1)antigensofredbloodcelllABOsystem(bloodt
19、yping)-veryimportantintransfusionlRhsystem(inChinese99%RH+)-HemolyticdiseaseofthenewborninducedbyRhincompatibilityABOsystem Blood antigen antibody in typing of RBC serum A A anti-B B B anti-A AB A,B - O - anti-A, anti-B 2)HLAsystem(Humanleukocyteantigen)-Relatedtotransplantation-Veryimportantinimmun
20、eregulationAutoantigen1)Degenerationofprotein2)ReleaseofsequesteredAg3)Forbiddenclonerejuvenate-common Ags sharedbydifferentspecies-nospecificityofspecies-Significance.Immunopathology.DiagnosisHeterophilicantigenTumorantigenTumorspecificAg(TSA)onlyexpressonthetumorcellsbutnormalcellsTumorassociatedA
21、g(TAA)high express on tumor cells but low on normalcellseg,AFPCEAEndogenousAgs:antigenssynthesizedwithincells-presentedbyclassMHCmolecules.ExogenousAgs:antigenscomesfromoutsideofthecells-presentedbyclassMHC molecules.3.Classificationbasedonnatureandsourceofantigen4.ClassificationbasedonotherslFuncti
22、ons:completeAg,haptenAglChemicalcomponentproteinpolysacchridenucleicacidlipidlProductionofAg:naturalAgartificialAgSectionVSuperantigen1.Superantigen(SAg):Substancethatcannon-specificallystimulatepolyclonalT/BcellsandinduceaverystrongimmuneresponsewithaextremelylowconcentrationSuperantigenConventiona
23、l AntigenSuperantigenAntigenThe mechanism of SAg is different from that of Ags.TCRMHCTcellSAg:exotoxin-enterotoxinABellSAg:SPA(staphylococcalproteinA)SignificanceofSAgImmuneactivationImmuneinhibitionImmunetoleranceWhat you should know by the end of this lectureDefinition and characteristics of antig
24、enDefinition of antigenic determinants, conformational determinants and linear determinantsDifference between T cell epitopes and B cell epitopesDefinition of common antigen and cross reactionDifference between TD-Ag and TI-AgHow can you classify different Ag? What is TSA,TAA, hetreophilic Ag, superantigen ?
