(3)-5抗原免疫学基础与病原生物学

AntigenContentConceptofantigenAntigencharacteristicsFactorsaffectingantigenicityEpitopeCommonantigenandcross-reactivityNon-specificimmunostimulantsAntigenpreparation1、Antigen,AgConcept:Asubstancethatcanmakeimmunecellsproduceimmuneresponseproducts(activatedTlymphocytesorantibodies),andspecificallybindthem.Immunogenicity免疫原性Reactogenicity反应原性Foreignness异物性Specificity特异性2、BasiccharacteristicsofantigenImmunogenicity:referstotheabilityofanantigentobindtolymphocytes(TCR,BCR),stimulatelymphocyteproliferation,differentiation,andproduceimmuneresponseproducts(suchassensitizedlymphocytesorantibodies).2、Thebasiccharacteristicsofantigen-immunogenicity,reactogenicityReactogenicity(antigenicity):referstotheabilityofanantigentospecificallybindtoimmuneresponseproducts(suchasantibodiesorsensitizedlymphocytes).AgAborCTLLmImmunogenicityReactogenicityCompleteantigenandhaptenantigenImmunogenicityReactogenicityForexampleCompleteantigen++Pathogen,serumHapten—+penicillinQuestion:Howdohaptensproduceantibodies?Whydohaptenssuchaspenicillincauseallergies?Conclusion:Hapten+carrier=completeantigenHapten-carrierphenomenonHapten-carrierphenomenoncanexplainthecauseofdrugallergyQuestion:

Whatroledoesthecarrierplayinthehapten-carrierphenomenon?Carriereffect:Duringthefirstandsecondimmunization,onlythehaptenisboundtothesamecarriertoproduceasecondimmuneresponseagainstthehapten.2、

Thebasiccharacteristicsofantigen-foreignness(exogenous,non-self)Referstothespeciesdifferencebetweenthesubstanceandthehost(MHCdifference).Itisthefirstconditiontodetermineantigenicity."Non-self"becomesanantigen.Farstrongnearweak:theimmuneresponsedependsonthedegreeofforeignbody.Thefarthertherelationshipbetweentheantigenandthehost,thestrongertheimmunogenicity.HeterogeneoussubstanceAllogeneicsubstanceOwnmatterSuchasheterologousserum,microorganisms,etc.BloodgroupantigenSuchasskingrafting,boneaugmentation>>Exceptions:Somehomologoustissuesareweaklyantigenic(suchascrystallin,thyroxin,braintissue);self-organizationchangestobecomeantigens;highlyconservedmacromolecules(collagen,cytochromeC).2、

Thebasiccharacteristicsofantigen-specificityReferstotheantigeninducingthebodytoproduceanadaptiveimmuneresponseanditsreactionwithimmuneresponseproductshasahighdegreeofspecificity.

IncludingimmunogenicspecificityandreactogenicspecificityIsthemostimportantfeatureoftheimmuneresponseItisthetheoreticalbasisforimmunedetectionandimmuneprevention.Themolecularbasisfordeterminingthespecificityofanantigenistheepitope.antigenicdeterminantReferstothespecialchemicalgroupintheantigenmoleculethatdeterminesthespecificityoftheantigenUsually5~15aminoacidresidues,5~7polysaccharideresiduesornucleotidesItisthematerialbasisofantigenspecificity.Itisthesitewheretheantigenbindsspecificallytothelymphocytereceptororantibody.Itishighlyspecific.3、EpitopeClassificationofepitope(accordingtospatialstructure)Linearepitope:Referstoapolypeptideconsistingofacontinuouslineararrangementofaminoacidresidues.Oftenlocatedinsidetheantigenmolecule.ItneedstobeprocessedforTcellrecognition.Conformationalepitope:Referstopolypeptideswhosesequencesarenotcontinuousbutareclosetoeachotherinspacetoformaspecificconformation.OftenlocatedonthesurfaceofantigenmoleculesforBcellstorecognize.E1E2Classificationofepitopes(accordingtothetypeoflymphocytesrecognized)Tcellepitope:AlinearepitopeprocessedandpresentedbyAPCforTcellrecognition.Bcellepitopes:TheepitopesrecognizedbyBcellsandtheirsecretedantibodiesarecollectivelycalledBcellepitopes.Bothlinearepitopesandconformationalepitopescanbeused.ConformationalepitopesandafewlinearepitopeslocatedonthesurfaceofantigenmoleculescandirectlyactivateBcellswithoutAPCprocessingandpresentation.NaturalantigensgenerallycontainbothTcellepitopesandBcellepitopes.Tcellepitope,BcellepitopeWhydosomeantigensweakentheirantigenicityafterenteringthebody?Thenumberofantigenepitopesinanantigenmoleculethatcanbindtoanantibody.Classificationofantigensbyantigenbindingvalence:monovalentantigen/multivalentantigenNaturalantigensaregenerallymultivalentantigens,containingmultipleandmultipleepitopes.Forexample,chickeneggproteinhas5epitopes,andthyroglobulinhasabout40epitopes.5、

Antigenbindingvalue6、

Epitopepredictionandverification•EpiplotEpitlot•BIMAS•epipredict•Predict•NetMHC1.0server•MAPPP_Predictionquery•mhcform•MHCPEP-adatabaseofMHCbindingpeptides•HLALigand-MotifOnlineDatabase•MHCDatabaseSearch•PredictionAlgorithmforproteasomalcleavages•NetChop2.0server•MPIDhomepage•IMGTDatabasesattheEBI•IPD-MHCSequenceDatabase•BciPepadatabaseofBcellepitopes•ProteinSecondaryStructurePredictionVerificationmethod:monoclonalantibodyPredictionmethod:

Biologicalsoftware7、FactorsaffectingantigenimmunogenicityChemicalnatureChemicalcompositionandstructureMolecularweightConformationandaccessibilityPhysicalstate7.1Antigenicfactors7.2Hostfactor7.3Operatingfactor:immunemethodOrganic>InorganicImmunogenicity:protein>carbohydrate>nucleicacid,lipid7.1.1Chemicalnature7.1Factorsthatdetermineantigenicity-antigen>>7.1.2Molecularweight>10kDa

PossibleCauses：a:Manyantigenepitopes,complexantigenmolecularstructureb:StayinthebodyforalongtimeandcontinuouslystimulateimmunecellsRelativity.Forexample,gelatinMW=100kD,veryweakantigenicity;insulinMW=5734,antigenicity7.1Factorsthatdetermineantigenicity-antigenBranchedchain>Straightchain,suchasgelatinWithbenzenering>WithoutbenzeneringSpherical>LinearParticulatematter＞SolublematterPolymer＞Monomer(polyaminoacid>singleaminoacid,suchaspolylysine,polyglutamicacid7.1.3Chemicalcompositionandstructure:themorecomplexthecompositionandstructure,thestrongertheantigenicity7.1Factorsthatdetermineantigenicity-antigenForexample,theantigenicityoflinearaminoacidsisveryweak,andtheantigenicityof+2%tyrosineisgreatlyenhancedThetypesofaminoacids,specialgroups,arrangementorder,position,spatialconfiguration,chargeproperties,hydrophilicityandphysicalstateaffectantigenicity7.1Factorsthatdetermineantigenicity-antigen7.1.4Conformationandphysicalstate,etc.Age:youngandmiddle-aged>juvenileandoldgeneticfactors：MHCgenecontrol.Differentspecieshavedifferentabilitiestorespondtothesameantigen.Differentindividualsofthesamespecieshavedifferentabilitiestorespondtothesameantigen.Gender:FemalesaremorecapableofproducingantibodiesthanmalesHealthstatus:Health>Infection,applicationofimmunosuppressiveagents7.2Factorsthatdetermineantigenicity-thebodyWay:non-oral>oralInjection:intradermal>subcutaneous>muscle>abdominalcavity>veinDose:Largercancausedeathorimmunetolerance;smallercannotproduceimmuneresponse.Thedosageofgranularantigen(suchasbacteria,etc.)issmall,andtheimmunogenicityisstrong;thedosageofsolubleantigen(suchasprotein)islarge,andmultipleimmunizationsoradjuvantsarerequired.Immunization:route,dose,adjuvant7.3Factorsthatdetermineantigenicity-operationScienceAdvances:Thefirstintradermaladjuvantvaccine(20180912),acombinationof3technologies:hollowmicroneedles,VLPs,adjuvantGLAReferstothepresenceofthesameorsimilarepitopebetweentwodifferentantigens.AgAAgBCommonantigenForexample,thereisacommonantigenbetweenRickettsiaandamoeba8、CommonantigenAphenomenoninwhichanantibodycanbindandreactwithmultiplecommonantigentables.Antigencross-reactivityAgAAgBCrossreactionUseofcommonantigensUniversalvaccine:suchastheMproteinofinfluenzavirusClinicaldiagnosis:suchasusingProteusantigeninsteadofRickettsiaantigentodetectRickettsiaantibodiesinthebodyHeterogeneousvaccines:suchasvacciniavaccinetopreventsmallpoxfluvirusItisacommonantigenthatexistsbetweendifferentspecies.In1911,discoveredbyForssman,alsoknownasForssmanantigenItcanexistinanimals,plants,microorganismsandhumans.Forexample,thecommonantigensharedbyhemolyticstreptococcusandhumanendocardiumorglomerularbasementmembraneisheterophilicantigen.Heterophilicantigen9、Thymus-dependentantigenandnon-thymus-dependentantigenAccordingtowhetherThcellsareneededtoassistclassificationThymusdependentantigen(TD-Ag):IthasTcellepitopesandBcellepitopes.ItmustrelyonthehelpofThcellstostimulateBcellstoproduceantibodies,alsoknownasTcelldependentantigens.Mostantigens(suchaspathogens,etc.).Thymus-independentantigen(thymusindependentantigen,TI-Ag):WhenstimulatingB1cellstoproduceantibodieswithoutthehelpofThcells,itisalsocalledTcell-independentantigen.ItisdividedintoTI-1andTI-2antigens.TI-1containsbothepitopesandmitogens,suchasbacterialLPS;TI-2antigencontainsmultiplerepeatedBcellepitopes,whichcanstimulateB1cellstoproduceanimmuneresponse,suchaspneumococcalcapsularpolysaccharide,flagellin,etc.InfantBcellsareimmatureandhavenoorlowresponsetoTI-2.10、AntigenpreparationNaturalantigens:microorganismswithstrongantigenicityHapten+carriercouplingRecombinantantigen:genecloning,expressionandpurificationArtificiallysynthesizedantigenpeptides:antigenepitopeprediction,antigenpeptidedesign,synthesis11、Non-specificimmunostimulantsSubstancesthatcannon-specificallystimulatetheimmuneresponseoflymphocytesarecalledimmunostimulants.SuperantigenAdjuvantMitogenReferstoatypeofantigenthatdoesnotneedtobeprocessedandpresentedbyantigen-presentingcells,andcandirectlyactivatemostTcellsatverylowconcentrationstoproduceastrongnon-specificimmuneresponse.11.1superantigen，SAgCommonantigenSAgAntigenpresentationneedunnecessaryConcentrationrequirementshighextremelylowSpecificitystrongnoNumberofactivatedTcellsfewmuchExogenous：Bacterialexotoxins,suchasStaphylococcusaureusenterotoxin,streptococcalexotoxin,etc.Endogenous：Virus-encodedprotein11.1superantigen，SAgAlsoknownasmitogen,it