ANTIGENSANDANTIBODIESSTRUCTUREOFIMMUNE結(jié)構(gòu)的免疫抗原和抗體

Antigens.Bacterialantigens.MajorHistocompatibilityComplex.Medicalbiology,microbiology,virology,immunologydepartment

Thenameantigens(Gk.antiagainst,genosgenus)isgiventoorganicsubstancesofacolloidstructure(proteinsanddifferentproteincomplexesincombinationwithlipidsorpolysaccharides)whichuponinjectionintothebodyarecapableofcausingtheproductionofantibodiesandreactingspecificallywiththem.

Antigenicsubstancesmusthavecertainproperties:

acolloidstructure,andsolubilityinthebodyfluids.

Antigenicpropertiesarepertinenttotoxinsofaplantorigin(ricin,robin,abrin,cortin,etc.),toxinsofananimalorigin(toxinsofsnakes,spiders,scorpions,phalangia,karakurts,bees),enzymes,nativeforeignproteins,variouscellularelementsoftissuesandorgans,

bacteriaandtheirtoxins,rickettsiaeandviruses.Antigens,consequently,arecharacterizedbythefollowingmainproperties:

1.theabilitytocausetheproductionofantibodies(antigenicity),2.theabilitytoenterintoaninteractionwiththecorrespondingantibodies(antigenicspecificity).Thefeaturesofmoleculesthatdetermineantigenicityandimmunogenicityareasfollows:1.Foreignness.2.MolecularSize.3.Chemical-StructuralComplexity4.AntigenicDeterminants(Epitopes)

Foreignness:

Ingeneral,moleculesrecognizedas"self”arenotimmunogenic;ie,wearetoleranttothoseself-molecules.Tobeimmunogenic,moleculesmustberecognizedas"nonself,"ie,foreign.MolecularSize:

Themostpotentimmunogensareproteinswithhighmolecularweights,ie,above100,000.Generally,moleculeswithmolecujarweightbelow10,000areweaklyimmunogenic,andverysmallones,eg,anaminoacid,arenonimmunogenic.Certainsmallmolecules,eg,haptens,

becomeimmunogeniconlywhenlinkedtoacarrierprotein.Chemicalnature:

Proteinandpolysaccharidesaremostantigenic.Lipidsandnucleicacidsarelessantigenic.Theirantigenicityisenhancedbycombinationwithproteins.Acertainamountofchemicalcomplexityisrequired,forexample,aminoacidhomopolymersarelessimmunogenicthanheteropolymerscontainingtwoorthreedifferentaminoacids.AntigenicDeterminants(Epitopes):

Epitopesare–smallchemicalgroupsontheantigenmoleculethatcanelicitandreactwithantibody.Anantigencanhaveoneormoredeterminants.Mostantigenshavemanydeterminants;ie,theyaremultivalent.AntigenepitopesAntigenepitopes

Hapten(incompleteantibody)isamoleculethatcannotinduceanimmuneresponsebyitself

butcanreactwithspecificantibody.Nevertheless,haptenscaninducearesponseifcombinedwithlargermolecules(normallyproteins)whichserveascarrier.Haptensareusuallysmall.Manydrugs,eg,penicillins,arehaptens,andthecatecholintheplantoilthatcausespoisonoakandpoisonivyisahapten.haptenNoantibidiesproduced

AntibodyagainstepitopeonantigenproteinImmunogenicantigenepitopeepitopehaptenImmunogenicantigenascarierforhapten

AntibodyagainstepitopeonantigenAntibodyagainstepitopeonhapten

Atypicalantigen:antibodyreaction:gram-negativebacterialpathogenmayhaveseveralantigens,orimmunogens(flagella,piliandcellwall)AntigenicstructureofabacteriumHNRNAProteinМ2ProteinМ1LipidmembraneAntigenicstructureofavirusAntigenicpropertiesofbacteria,toxins,rickettsiaeandviruses,usedinthepracticeof

reproducingartificialimmunityagainstinfectiousdiseases,areofmostpracticalimportance.

Whentheantigenicstructuresofthehostaresimilarto

thoseofthecausativeagent,themacroorganism

isincapableofproducingimmunity,astheresultofwhichthediseasefollowsagravercourse.Itispossiblethatinindividualcasesthecarrierstateandinefficacyofvaccinationareduetothecommoncharacterofthemicrobialantigensandtheantigensoftheperson'scells.Ithasbeenestablishedthathumanerythrocyteshaveantigensincommonwith

staphylococci,streptococci,theorganismsofplague,E.coli.Salmonellaparatyphi,Shigellaorganisms,smallpoxandinfluenzaviruses,andothercausativeagentsofinfectiousdiseases.Suchaconditioniscalledantigenicmimicry.Isoantigens

arethosesubstanceswhichhaveantigenicpropertiesandarecontainedinsomeindividualsofagivenspecies.Isoantigensofleukocytes,bloodplatelets,lymphocytes,granulocytes,bloodsera,liver,andkidneysandinter-organ(cellnuclei,mitochondria,ribosomes,etc.)andpathological(cancerous,bum,radiation)isoantigenshavebeenrevealed.Isoantigens

havebeenfoundintheerythrocytesofanimalsandman.Atfirstitwasestablishedthatinhumanerythrocytestherearetwoantigens(AandB),andinthesera—beta-andalpha-antibodies.Onlyheterogenicantigensandantibodies(agglutinins)canbefoundinhumanblood.Onthebasisofantigenicstructuretheerythrocytesofallpeoplecanbesubdividedinto4groups(A,B,ABand0).Thesedataaretakenintoaccountduringbloodtransfusion.Autoantigens

aresubstancescapableofimmunizingthebodyfromwhichtheyareobtained.Selfantigensareordinarilynon-antigenic,notnormallyfoundfreeincirculationortissuefluids,arenotrecognizedasselfantigens.Thus,theybecomemodifiedandarecapableofbearinganantigenicfunction.

Autoantigens

Thesesubstancesinclude

theeyelens,spermatozoids,homogenatesoftheseminalgland,skin,emulsionsofkidneys,liver,lungsandothertissues.Autoantigens

Underordinaryconditionstheydonotcomeincontactwiththeimmunizingsystemsofthebody,thereforeantibodiesarenotproducedagainstsuchcellsandtissues.However,ifthesetissuesareinjured,thenautoantigensmaybeabsorbed,andmaycausetheproductionofantibodieswhichhaveatoxiceffectonthecorrespondingcells.

Theoriginationofautoantigensispossibleundertheinfluenceof

cooling,radiation,drugs(amidopyrine,sulphonamides,preparationsofgold,etc.),virusinfections"(viruspneumoniasandmononucleosis),acterialproteinsandtoxinsofstreptococci,staphylococci,tuberclebacilli,paraproteins,asepticautolysisofbraintissue,andotherfactors.HistocompatibilityantigensTherearetheantigenspresentonthecellsofeachindividualofspecies.Theseproteinsarealloantigens;ie,theydifferamongmembersofthesamespecies.Theseantigensareencodedbygenesknownashistocompatibilitygeneswhichcollectivelyconstitutemajorhistocompatibilitycomplex(MHC),Thesearelocatedontheshortarmofchromosome6.MajorHistocompatibilityComplexMHCproductspresentonthesurfaceofleucocytesareknownashumanleukocyteantigens(HLA).Thesuccessoftissueandorgantransplantsdependsonthedonor'sandrecipient'shumanleukocyteantigens(HLA).IftheHLAproteinsonthedonor'scellsdifferfromthoseontherecipient'scells,animmuneresponseoccursintherecipient.MajorHistocompatibilityComplex

Threeofthesegenes(HLA-A,HLA-B,andHLA-C)codefortheclassIMHCproteins.SeveralHLA-DlocideterminetheclassIIMHCproteins,ie,DP,DQ,andDR.TherearemanyallelesoftheclassIandclassIIgenes.Forexample,thereareatleast47HLA-Agenes,88HLA-Bgenes,29HLA-Cgenes,andmorethan300HLA-Dgenes,butanyindividualinheritsonlyasinglealleleateachlocusfromeachparentandthuscanmakenomorethantwoclassIandIIproteinsateachgenelocus.

Expressionofthesegenesiscodominant,ie,theproteinsencodedbyboththepaternalandmaternalgenesareproduced.Eachpersoncanmakeasmanyas12HLAproteins:3atclassIlociand3atclassIIloci,frombothchromosomes.BetweentheclassIandclassIIgenelociisathirdlocus,sometimescalledclassIII.Thislocuscontainsseveralimmunologicallyimportantgenes,encodingtwocytokines(tumornecrosisfactorandlymphotoxin)and-twocomplementcomponents(C2andC4).ClassIMHCProteins.Theseareglycoproteinsfoundonthesurfaceofvirtuallyallnudeatedcells.Thereareapproximately20differentproteinsencodedbytheallelicgenesattheAlocus,40attheBlocus,and8attheClocus.ClassIIMHCProteins.Theseareglycoproteinsfoundonthesurfaceofcertaincells,includingmacrophages,Bcells,dendriticcellsofthespleen,andLangerhanscellsoftheskin.BIOLOGICIMPORTANCEOFMHC

TheabilityofTcellstorecognizeantigenisdependentonassociationoftheantigenwitheitherclassIorclassIIproteins.Forexample,cytotoxicTcellsrespondtoantigeninassociationwithclassIMHCproteins.Thus,acytotoxicTcellthatkillsavirus-infectedcellwi