醫(yī)學免疫學復習資料：名解

PAGEPAGE7IMMUNOLOGY(TERMS)1.Immunity:“aconditionofbeingabletoresistaparticulardiseaseespeciallythroughpreventingdevelopmentofapathogenicmicroorganismorbycounteractingtheeffectsofitsproducts”2.Immunology:isthestudyofourprotectionfromforeignmacromoleculesorinvadingorganismsandourresponsestothem.3.Innateimmunityevolveswiththegermlineandinvolvesreceptors,enzymesandcellsthatdetectconservedaspectsofmicrobesandparasites.Itisthe1stlineofdefense.Nospecificity,nomemory.4.AdaptiveimmunityisprovidedbyT&Blymphocytes.Itisthe2ndlineofdefense.Ithastwoimportantcharacteristics:Immuneresponseishighlyspecificfortheantigenthattriggeredit.Exposuretoantigencreatesanimmunologic“memory.”5.Primarylymphoidorgans:Lymphoidorgansincludeprimary(bonemarrow&thymus)andsecondarylymphoidorgansandtissues(lymphoidnodes、spleen、MALT)Primarylymphoidorgansaretheplacewherelymphocytesdevelopandmature.LymphocytesincludesBcellandTcell,respectivelyoriginatingfrombonemarrowandthymusandmediateshumoralandcellularimmunity.6.Secondarylymphoidorgans:Secondarylymphoidorgansaretheplacethatimmuneresponseshappen,whichincludelymphnodes,spleen,tonsilandMALT.Lymphnodesdraintheconnectivetissuesofthebody.Thespleendrainstheblood.MALTareresponsibleforlocalinfection.7.MALT:Themajority(50%)oflymphoidtissueinthehumanbodyislocatedwithintheliningofthemajortracts,includingrespiratory,digestiveandgenitourinarytracts.Thisisbecausethesearethemainsitesofentryformicrobesintothebody.Thesearecollectivelycalledthemucosa-associatedlymphoidtissues(MALT).8.Antigensaremoleculeswhicharerecognizedbyreceptorsonlymphocytes.Blymphocytesusuallyrecognizeintactantigenmolecules,whileTlymphocytesrecognizeantigenfragmentsonthesurfaceofantigenpresentingcells.9.Epitope:Antigenmoleculeseachhaveasetofantigenicdeterminants,alsocalledepitopes.EpitopesaremolecularshapesrecognizedbyantibodiesandTcellsoftheadaptiveimmunesystem.10.ClonalselectionEachlymphocyteisgeneticallyprogrammedtobecapableofrecognizingessentiallyonlyoneparticularantigen.Whenanantigenbindstothecellthatcanrecognizeit,itisinducedtoproliferaterapidly.Withinafewdaysthereareasufficientnumbertomountanadequateimmuneresponse.Inanotherwords,theantigenselectsforandgeneratesthespecificclonesofitsownantigen-bindingcells,aprocesscalledcloneselection.Inbrief:cloneselectioninvolvesrecognitionofantigenbyaparticularlymphocyte,thisleadtoclonalexpansionanddifferentiationtoeffectorandmemorycells.11.Opsonization:Thissisaprocessofmakingamicrobeeasiertophagocytose.Anumberofmoleculescalled“opsonins”dothisbycoatingthemicrobesandaidattachmentofthemicrobetothephagocyteandalsotriggeractivationofphagocytosis.opsoninsincludethecomplementcomponentC3bandantibodywhichactingasabridgebetweenantigenandphagecytes.12.NKcellsbelongtolymphocytefamily.ButincontrasttoallTandBlymphocytes,NKcelldonotexpressantigen-specificreceptorsanddonotpossesstheadaptivepropertyofmemorycelldevelopment:theyarethereforconsideredtoformpartoftheinnateimmunesystem.However,likeTc,theirmainfunctionistokillinfectedcellandtumorcellsusingsimilarmechanismtothoseofTccellstoinduceapoptosisoftheirtargets.NKcellarealsoabletokilltargetscoatedwithIgGviatheirreceptorforIgG.ThispropertyisreferredtoasADCC.13.DCsarerequiredbyTcelltoenablethemtorespondtoantigens.DCsaremostimportantantigenpresentingcellsknownsofarandaretheinterfaceofinnateandadoptiveimmunity.Functions:Antigenup-takinginperipheralsites&antigenpresentationinlymphnodes.14.Complement:ThecomplementsystemisanimportantcomponentofinnateimmunityItcanbeactivatedbytheclassicalandalternativepathways,bothpathwayswilleventuallyleadtothelyticpathwaywhichfeaturedbytheformationofMAC.Functionofcomplement:anaphylaxis(C3a,C5a),chemotaxis(C5a)，opsonization(C3b,C4b),lysis(C56789)15.Interferonsareproteinsinvolvedinprotectionagainstviralinfections.Thetwokindsofinterferon,typeIandtypeII,havedifferentcellularoriginsandmediatearangeofdifferentactivities.Theyinterferewithviralreplicationbutalsoaresignalingmoleculesbetweencells.16.lymphocytetrafficandrecirculationLymphocytesproducedintheprimarylymphoidorgans(thymus-T,bonemarrow-B)migrateviathebloodstreamtothesecondarylymphoidorgans/tissueswheretheycarryoutthefunction.Theydonotstayinonesitebutcontinuallyrecirculatethroughthebodyinsearchofantigens.17.Affinityisthetightnessofbindingofanantibodybindingsitetoanantigenicdeterminant(epitope)thetighterthebinding,thelesslikelytheantibodyistodissociatefromantigen.18.Valenceisthemaximumnumberofepitopeswithwhichtheantibodycanreact.19.Avidity:antibodybindsamultivalentantigenistermedavidity,todifferentiateitfromtheaffinityofasingleantigenicdeterminantforanindividualcombiningsite.Antibodyavidityindicatestheoverallstrengthofinteractionbetweenantibodyandantigen.20.Isotype:Thesearegeneticmarkersonimmunoglobulinssharedbyalltheindividualofsamespecies.Thegenesforisotypicvariantsarepresentinallhealthymembersofaspecies.Forexample,thegenesforγ1,γ2,γ3,γ4,μ,α1,α2,δ,ε,κandλchainsareallpresentinthehumangenome,andarethereforeisotypes.21.Allotype:Thesearegeneticmarkersonimmunoglobulinsthatsegregatewithinthespecies.Thisreferstogeneticvariationbetweenindividualswithinaspecies.Forexample,thevariantofIgG3calledG3m(b0)ischaracterizedbyaphenylalanineatposition436oftheγ3heavychain.Itisnotfoundinallpeopleandisthereforeanallotype.Allotypesoccurmostlyasvariantsofheavychainconstantregions.22.Idiotype:Theseareuniqueantigenicdeterminantassociatedwithantigenbindingsitesofantibodiesandaretheresultsofthedifferentaminoacidsequenceswhichdeterminetheirspecificities.Variationinthevariabledomain,particularlythehypervariableregions,producesidiotypes.Thesedeterminethebindingspecificityoftheantigen-bindingsite.23.CDRs:Attheaminoacidlevel,thevariableregionofantibodyiscomprisedofthreeregionsofextremevariability(hyervaribleregion).Theyarecalledcomplementarity-determiningregions,orCDRs.24.FRs:InterspersedamongtheCDRsareframeworkregions(FRs)whicharelessvariableandmoreevolutionarilyconserved.Atthethree-dimensionallevel,thethreeCDRsofeachchainconvergetoformacombiningsitewhichrecognizetheantigenicdeterminant(epitope).25.Monoclonalantibody:In1975,KohlerandMilsteindevelopedaproceduretocreatecelllinesproducingpredetermined,monospecificandmonoclonalantibodies.Thebasictechnologyinvolvesfusionofanimmortalcell(amyelomatumorcell)withaspecificpredeterminedantibody-producingBcellfromimmunizedanimalsorhumans.Theresultinghybridomacellisimmortalandsynthesizeshomogeneous,specific,mAbwhichcanbemadeinlargequantities.26.ADCC：ANTIBODY-DEPENDENTCELL-MEDIATEDCYTOTOXICITY–Thelinkingofantibodyboundtotargetcells(virusinfectedcells,orsometumorcells)withFcRofnaturalkillercells(NKcells),neutrophils,macrophages,oreosinophilscanresultinkillingofthetargetcell.27.cytokinesDefinition:Cytokinesaresmallmolecules,secretedbycellsinresponsetoastimulus.Function:Asagroup,cytokinesinducegrowth,differentiation,chemotaxis,activationand/orenhancedcytotoxity.Theyareusedforstrengtheningcommunicationsbetweencells.28.Tolllikereceptors(TLR)Tolllikereceptorsareafamilyofproteinsofwhichthereareatleast5knownmembers.UsingTLRs,innateimmunecellscandetectandrespondtoinfectionbyrecognizingconservedmotifsofmicrobes.TLRstransmitsignalsaboutmicrobialconstituentstothenucleus,thusregulatingthetypeofgenesexpressed,andthesubsequentresponse.29.PositiveselectionofTcells:TcellsthatexpressaTCRthatcanbindweaklytoselfMHCaresparedfromdeathandarepositivelyselectedtosurvive.30.NegativeselectionofTcells:Tcellsthatreactstronglytoself-antigensonMHCareeliminated.OnlythoseTcellsthatcanreacttoMHC,butdonotbindstronglytoself-antigensemergeasmatureTcellsfromthethymus.31.CD:cellsurfacemoleculescanberecognizedbyparticularmonoclonalantibodies.AllofthemAbsthatreactwithaparticularmembranemoleculearegroupedtogetherasaclusterofdifferentiation(CD).32.MHC:majorhistocompatibilitycomplexItwasidentifiedthatthehistocompatibility(theabilitytoacceptgraftsfromanotherindividual)dependedonthedonorandrecipientsharingthesameMHCgenetype.Itwasprovedthenthatthegeneisaverylarge,containingmorethan100separategeneloci,butthemoleculeswhichdeterminegraftrejectionarealimitedgrouptermedclassIandclassIIMHCgenesthatmapneartoeachotheronasinglechromosome.That'swheretheterm,majorhistocompatibilitycomplexcomesfrom.33.TH1:CD4+THelpercells(TH)arefurtherdividedinto2mainclasses,TH1andTH2,andmaturationintothesetypesisdeterminedbythemicroenvironment.TH1cellsarestimulatedtomatureduetothepresenceofbacteria,viruses,fungi,protozoa.Theystimulatemacrophageactivation,andsupportmaturationofCytotoxicTcells.TheyreleaseIL-2,IFN-Y,TNF-B,andarelinkedtocellmediatedinflammation,andDelayedTypeHypersensitivity.ActivatemacrophagesandcytotoxicTcellstoaggressivelyingestantigenandtokillingestedmicrobes.34.TH2:StimulateBcellstodifferentiateintoantibody-producingplasmacells.BcellswillonlyundergoisotypeswitchingafterreceivingTcellhelp.TheIgclassthataBcellswitchestoisspecifiedbythetypesandbalanceofcytokinessecretedbythehelperTcell.35.TcareCD8+cells:alsocalledcytotoxicTcellswhichkillvirallyinfectedcells.OnceactivatedcytotoxicTcellsactontargetcellsinfectedpathogenandkillthembyapoptosis(throughporferindependedkillingandfasdependedkilling).Thisstopsintracellularpathogensreproducingandfurtherinfectinghostcells.36.2-signaltheoryforTcellactivation:ApopularmodeltoexplaintherequirementofTcellactivationisthetwo-signalhypothesis.Inthismodel,signaloneisderivedfromtheTCRaftertriggeringbyantigenicpeptidepresentedbyMHCandsignaltwoisdeliveredthroughcostimulatorymoleculesexpressedonthesurfaceofTcells,BcellsandAPCs.37.Co-stimulatorymolecules:the2ndsignalforTcellactivationisprovidebythemoleculesonAPCs,whicharecalledcostimulators.Intheabsenceofcostimulation,Tcellsthatencounterantigenseitherfailtorespondanddiebyapoptosisorenterastateofunresponsivenesscallanergy.ThebestcharacterizedCMisCD28-B7.38.Immunetolerance:Itreferstoanantigeninducedspecificunresponsiveness.Itisanantigen-induced,activeprocess.Likeimmunologicresponse,itisantigenspecific.Likeimmunologicresponse,itcanexistinBcells,Tcellsorboth.Likeimmunologicresponse,itseasiertoinduceandlastslongerinTcellsthaninBcell.39.CentraltoleranceistheprocesswherebyimmatureTandBcellsacquiretolerancetoselfantigensduringmaturationwithintheprimarylymphoidorgans/tissues.Itinvolvestheeliminationofcellswithreceptorsforselfantigens.Mechanism:clonaldeletion40.Peripheraltoleranceistheprocesswherebymaturelymphocytesacquiretolerancetoselfantigensinperipheraltissues.Mechanismclonalanergy(BandT),AICD41.AICD:activationinducedcelldeath.Fas/FasLinteractionisdirectlyresponsibleforAICD.Thismayofprimarybenefitinmaintainingimmunologicalaswellasphysiologicalhomeostasisbyeliminatingunnecessarycellsthroughapoptosis.ActivatedTlymphocytescanexpressboththereceptorproteinFasanditsligandFasL,whereasBcellsmainlyexpressFas.Fas/FasLinteractionleadstocelldeath.42.TSA(tumorspecificantigens):uniquetotumorcellsbutarerare.43.TAA(tumorassociatedantigens):arealsofoundonsomenormalcells.44.OncofetalantigensarethusnotTSAnoristheirpresent,evenathighconcentration,intheserumdiagnosticofcancer,becausehighlevelscanresultfromnon-neoplasticdiseasesincludingchronicinflammationofthebowelorcirrhosisoftheliver.However,thequantitationofthesemoleculesintheserumcanbeusedtoevaluatethetumorburdenandeffectivenessofdrugtreatment.45.TCR-CD3complex:ATCRcomplexiscomposedofoneheterodimericTCR,plusa5-polypeptideCD3complexwhichisinvolvedincellsignallingforTcellactivation.CD3istheactivationcomplexfortheTCR.TheTCRonlyrecognizesantigen/MHCcomplexexpressedonthesurfaceofcells.Bindingofantigen/MHCtotheTCRstimulatesCD3.CD3thensendsanactivationsignaltotheinsideoftheTcell.44.HLA:HLA(humanlymphocyteantigen)ishumanMHC(majorhistocompatibilitycomplex)Itwasidentifiedthatthehistocompatibility(theabilitytoacceptgraftsfromanotherindividual)dependedonthedonorandrecipientsharingthesameMHCgenetype.Itwasprovedthenthatthegeneisaverylarge,containingmorethan100separategeneloci,butthemoleculeswhichdeterminegraftrejectionarealimitedgrouptermedclassIandclassIIMHCgenesthatmapneartoeachotheronasinglechromosome.That'swheretheterm,majorhistocompatibilitycomplexcomesfrom.47.BCR-Igα/βcomplexBcellreceptorismembrane-boundimmunoglobulinIgM,thefunctionofBCRistorecognizeantigensignalsandthenactivesEachchainhasaconstantregionandavariableregion,similartoanantibody.ABCRcomplexiscomposedofoneBCR,plus2Igɑ/IgbcomplexwhichisinvolvedincellsignallingforBcellactivation.TheBCR-Igα/βcomplexrecognizesandbindantigensandsendantigensignalstothenuclearofBcells.48.Superantigens:Someproteinproductsofbacteriaandvirusesproduceproteinsknownassuper-antigensthatbindtolateralsurfaceofMHCIImolecules(notinthepeptidebindinggroove)andtheVregionofthebsubunitoftheTCR.Theseantigensarenotprocessedintopeptidesasconventionalantigens,butareabletobindtoaspecificfamilyofTCR.49.Vaccination–termnowusedtoexplainhowhealthysubjectsareinoculatedwithattenuated(weakened)strainsofpathogenstoinduceACQUIREDprotection(Activeimmunization).TheaimofvaccinationistoinducememoryinTand/orBcellsthroughtheinjectionofanonvirulentantigenpreparation.Thus,intheeventofanactualinfection,theinfectiousagentand/oritstoxinismetbyasecondaryratherthanaprimaryresponse.50.Passiveimmunization:Passiveimmunizationistheadministrationofpreformedantibodies(usuallyIgG)eitherintravenouslyorintramuscularly.ItisusedtoproviderapidprotectionincertaininfectionssuchasdiphtheriaortetanusorintheeventofaccidentalexposuretocertainpathogenssuchashepatitisB.Itisalsousedtoprovideprotectioninimmunecompromisedindividuals.51.Activeimmunization:activeimmunizationistheadministrationofvaccinescontainingmicrobialproducts(withorwithoutadjuvants)inordertoobtainlongtermimmunologicalprotectionagainsttheoffendingmicrobe.52.Adjuvants:nonlivingvaccines,especiallythoseconsistingofsmallmoleculesrequiretheinclusionofagentstoenhancetheireffectiveness.Theseagents(adjuvants)includemicrobial,syntheticandendogenouspreparationshavingadjuvantactivity.53.IDD:Immunodeficiencydisease(IDD)ischaracterizedbytheprogressivelossordepressionofimmunefunctioncausedbycongenitalhypoplasiaorpostnatalfactors.AccordingtothereasonsinIDD:Primaryimmunodeficiencydisease(PIDD)andSecondaryimmunodefici