section 3 antigen

Section3Antigens 1 Mastertheconcept characteristicoftheantigen andthefactorsinfluencingimmunogenicity chemicalnature moleculesize foreignness andgeneticcharacteristicsofthehost 2 Masterantigenicdeterminant commonantigen 3 Understandantigencategory 4 knowsuperantigen5 Understandtheimportantantigeninmedicine AntigenandAdaptiveimmunity Bcells antigen EffectorBcells memoryBcells Plasmacell Tcells antigen EffectorTcells memoryTcells CTLs Ths Antigen Ag Chapter1Propertiesofantigen SubstancesthatcombinespecificallywithaBorTcell santigen bindingreceptorscantheninduceanimmuneresponsearecalledantigens Antigen Ag AntigenbindingcausescytotoxicTcells MemoryTcell ActivatedcytotoxicTcell Antigenbindingtriggersreleaseofantibodies MemoryBcell ActivatedBcell Antibodies Chapter2Characteristicsofantigen 1 immunogenicity 2 antigenicity Theantigenmoleculegenerallyposetwonatures thatis 1 Immunogenicity Immunogenicityistheabilitytoinduceahumoraland orcellmediatedimmuneresponse includinginduceproductionofantibodyandeffectorlymphocytes ActivatedBcell antibody ActivatedCTL 2 antigenicity Antigenicityistheabilitytocombinespecificallywiththefinalproductsoftheaboveresponses i e antibodyand orcell surfacereceptors 1Specificity SpecificityofantigenThecharacteristicthatantigenonlybindstheantibodyandsensitizedlymphocytespecifically iscalledspecificityofantigen Specificity Landsteiner Theeffectofcompositionandspatialstructureofchemicalgrouponthehapten antibodyspecificity 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 Antigenicdeterminantsorepitopesaretheimmunologicallyactiveregionsofanimmunogenthatbindtoantigen specificmembranereceptorsonlymphocytes TCR BCR ortosecretedantibodies 1 Antigenicdeterminantsorepitopes EpitopeorAntigenicDeterminant antigen antigen antigen 1ConformationalepitopeNonsequentialpolypeptidesorpolysaccharideonthesurfaceofthemolecules Nativeconformation 2linerepitopeAsequentialaminoacidfragment Lineardeterminant Insideoftheantigenmolecule Structureofepitopes Thepropertiesofantigenicdeterminants ConformationalandLinearEpitope TcellEpitopeandBcellEpitope Inimmuneresponse theepitopesthatTCRandBCRrecognizeisdifferent andarecalledTcellepitopeandBcellepitope separately 1 humanpancreaticglucagonwasinoculatedintothemouse 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 NH3 19 20 21 22 23 24 25 26 27 28 29 COOH 2 ProductionofspecificantibodyandTeffectorcell NoepitopewasfoundtoberecognizedbyTcellandBcellsimultaneously COOH 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 NH3 19 20 21 22 23 24 25 26 27 28 29 TcellEpitopeandBcellEpitope TcellEpitope TcellEpitope BcellEpitope Digested onsurfaceofmolecule antigen antibodyCDR3 epitope Bcellepitope isrecognizedbyBCRandantibody conformationaldeterminants i Bcellepitope Hemaglutinin HA DeterminantsrecognizedbyBcells 1 Composition AntigenicdeterminantsrecognizedbyBcellsandtheantibodiessecretedbyBcellsarecreatedbytheprimarysequenceofresiduesinthepolymer linearorsequencedeterminants and orbythesecondary tertiaryorquaternarystructureofthemolecule conformationaldeterminants 2 Size Ingeneralantigenicdeterminantsaresmallandarelimitedtoapproximately4 8residues aminoacidsandorsugars Thecombiningsiteofanantibodywillaccommodate ii Tcellepitope ThepeptidethatispresentedbyMHCmoleculeandrecognizedbyTCRiscalledTcellepitope TCR MHC HIVpeptide TCRrecognizeMHC antigenicpeptide TCR Antigenicpeptide MHC II Tcell APC Ep1 Ep2 Ep3 TCellepitope AntigenicpeptidesrecognizedbyTcellformtrimolecularcomplexeswithaTCRandanMHCmolecule Dependontheaminoacidsequenceofthepeptide RelevanttotheexpressionofMHCmoleculeofthehost DeterminantsrecognizedbyTcells Composition AntigenicdeterminantsrecognizedbyTcellsarecreatedbytheprimarysequenceofaminoacidsinproteins Tcellsdonotrecognizepolysaccharideornucleicacidantigens ThedeterminantsneednotbelocatedontheexposedsurfaceoftheantigensincerecognitionofthedeterminantbyTcellsrequiresthattheantigenbeproteolyticallydegradedintosmallerpeptides FreepeptidesarenotrecognizedbyTcells ratherthepeptidesassociatewithmoleculescodedforbythemajorhistocompatibilitycomplex MHC anditisthecomplexofMHCmolecules peptidethatisrecognizedbyTcells ComparisonofepitopeofTandBcell TcellepitopeBcellepitope ReceptorTCRBCR MHCmoleculerequiredtodisplaynonerequiredprocessedantigen characterlinerpeptidesnaturalpolypeptide LPS polysaccharide organiccompound 5 15aminoacids 5 7monosaccharideor5 7nucleotide Epitopetypelinerconformational liner sideanyonthesurface size 8 12aminoacids CD8 12 17aminoacids CD4 2 Commonantigenandcross reaction EachBcelldeterminantinducesproductionofaspecificantibody Therebyacomplicatedantigencaninduceproductionofmultiplyantibodies complicatedantigen Asameorsimilarantigenicdeterminantthatexistsbetweenthetwodifferentantigensiscalledcommonantigen Thereactionthatantibodyreactswithsameorsimilarantigenicdeterminantbetweenthedifferentantigensiscalledcross reaction Immunologicalmemory ABcowpoxDE Anti Cowpoxantibody cowpoxBmcell Anti CowpoxantibodyagainstSmallpox SmallpoxBmcell cowpoxBmcell days FirstresponsetoantigenCowpox AntigenCowpoximmunity AntigenSmallpoxAntigenB immunity Antibodyconcentration FirstresponsetoantigenB SecondaryresponsetoantigenSmallpox Foreignnessisthecentreofimmunogen Thegreaterofthephylogeniticdistancebetweentwospecies thegreaterthestructuraldisparitybetweenthem Variouspathogens animalprotein homologuous Self moleculethathasnotbeenexposedtoimmaturelymphocytesduringlymphocytedevelopmentmaybelaterrecognizedasnonself orforeign bytheimmunesystem 2Foreignness 5 1 3 HaptenandCarrier 1Hapten somesmallmolecules calledhaptens areantigenicbutincapable bythemselves ofinducingaspedificimmuneresponse Inotherwords theylackimmunogenicity 2carrier Chemicalcouplingofhaptentoalargeproteinyieldsanimmunoginichapten carrierconjugate Thesubstancethatcanmakethehaptenbeimmunogenic iscapableofinducingimmuneresponse arecalledcarrier Hapten Haptenshavethepropertyofantigenicitybutnotimmunogenicity Asubstancethatisnon immunogenicbutwhichcanreactwiththeproductsofaspecificimmuneresponse smallmolecules immuneresponse carrier hapten carrier completeantigen Chapter3Factorsinfluencingimmunogenicity 1Physicochemicalnatureofantigens 1 chemicalnatureglycoprotein lipoprotein polysaccharide LPSDNA chromosome histoneintheactivatedlymphocyte Auto antibodyforself DNA histone Antinuclearantibody ANA Autoimmunediseases 2 moleculesize 10kD 100kD 10kD immunogens Strongimmunogens Poorimmunogens Thehigheristhemoleculeweight ThemoreareantigenicdeterminantsThemorecomplexistheantigenicstructure Notbedegradatedeasilier Stimulatingimmunecellcontinuously Highimmuneresponse 3 complicatedchemicalstructure GlutinMW 100kD Straightchainaminoacid AddAromaticaminoacid 2 tyrosine poorimmunogenicity betterimmunogenicity 4 conformationandaccessibilityofthemolecule Tyrosinepoly alanineGlutanpoly lysine immunogenicity 1 GeneticcharacteristicsofthehostGeneticcontrolofimmuneresponsiveness largelyconfinedtogeneswithintheMHC 2 Age sex andstateofhealth Infection useofimmuneinhibitor 2Effectofhost Chapter4Classificationofantigens 1 DependonwhetherneedtheThforproducingtheantibody thymusdependentantigen TD Ag thymusindependentantigen TI Ag TIandTDantigen 1 2 CD40 CD40L Bcell Bcell Thcell TI antigen TDantigen CD4 1 Thymusdependentantigen TD Ag T dependentAntigens donotdirectlystimulatetheproductionofantibodywithoutthehelpofTcells Proteins Structurallycharacterizedbyafewcopiesofmanydifferentantigenicdeterminants 2 Thymusindependentantigen TI Ag T independentAntigens directlystimulatetheBcellstoproduceantibodywithouttherequirementforTcellhelpPolysaccharides Characterizedbythesameantigenicdeterminantrepeatedmanytimes agram negative E coli plasmamembraneandcellwall Figure15 3 2Dependontherelationshipwithhost 1 XenogenicAg Theantigenfromdifferentspeciesiscalledxenogenicantigen MicroorganismAnimalimmuneserumfortherapy horseserum antitoxin Horseserumantitoxinspossesdualnatures i Specificantibody neutralizationoftoxin ii Xenogenicantigen stimulateproductionofantibodyagainsthorseserum hypersensitivity 2 AllogenicAg Theantigensfromdifferentindividualsofthesamespeciesarecalledallogenicantigen HumanallogenicAg bloodtype RBC ant