醫(yī)學(xué)免疫學(xué)甲全冊配套完整課件

醫(yī)學(xué)免疫學(xué)甲全冊配套完整課件IntroductionIMMUNOLOGY曹雪濤主編《醫(yī)學(xué)免疫學(xué)》第六版人民衛(wèi)生出版社2013金伯泉主編《醫(yī)學(xué)免疫學(xué)》第五版人民衛(wèi)生出版社2008龔非力主編《醫(yī)學(xué)免疫學(xué)》第三版科學(xué)出版社2009AbbasAK,etal.CellularandMolecularImmunology.7thed.ElsevierSaunders,2012JanewayCA,etal.Immunobiology.8thed.GarlandSciencePublishing,2012References

Immunologyisonfrontiersoflifesciences

Immunologyisoneofthemainpillarsfordevelopmentofbasicandclinicalmedicine

ImmunologyisconnectedtightlywithbiotechnologyanditsindustrializationAnumberofmysteriesareunderexplorationinimmunologyWhystudyImmunology?ImmunologyisadifficultFirst,therearelotsofdetails,andsometimesthesedetailsgetinthewayofunderstandingtheconcepts.Aseconddifficultyinlearningimmunologyisthatthereisanexceptiontoeveryrule.Thethirddifficultyinstudyingimmunologyisthatourknowledgeoftheimmunesystemisstillevolving.IntroductionConceptofImmunityImmuneResponseImmuneCellsTissuesandOrgansoftheImmuneSystemImmunopathologyImmunity1.Immunity:referstoallmechanismsusedbythebodyasprotectionagainstenvironmentalagentsthatareforeigntothebody.(torecognizeandeliminateforeignsubstances)2.Agents:microorganisms(viruses,bacteriaetc)andtheirproducts,foods,chemicals,pollen,tumorcells,etc.3.Immunesystem:immunetissuesandorgans,immunecells,immunemoleculesIntroduction4.Immuneresponse:thecoordinatedreactionofthemoleculesandcellsintheimmunesystemtoaforeignagent.Benefits:protectthehostfromdiseasesDamagingeffects:causetissuedamage5.Immunology

isthestudyofthewaysinwhichthebodydefendsitselffrominfectiousagentsandotherforeignsubstancesinitsenvironment.Threefunctionsofimmunesystem:

(1)immunologicdefence(2)immunologicsurveillance(3)immunologichomeostasisTheDangerModel:ARenewed

SenseofSelfPollyMatzingerTheSelf-NonselfModelsTheInfectious-Nonself(INS)ModelTheDangerModelIntroductionConceptofImmunityImmuneResponseImmuneCellsTissuesandOrgansoftheImmuneSystemImmunopathologyBriefhistoryofImmuneResponseImmuneResponseIntroduction

Innateimmuneresponse

naturalimmuneresponse

non-specificimmuneresponse

Adaptiveimmune

response

acquiredimmuneresponse

specificimmuneresponseInnateimmunityItreferstoanyinbornimmunitythatisalreadypresentthefirsttimeapathogenisencountered.Itdoesnotrequirepriorexposureandisnotmodifiedsignificantlybyrepeatedexposurestothepathogenoverthelifeofanindividual.IntroductionInnateimmuneresponse

Physiologicalbarriersskinmucousmembranes

Phagocytosispolymorphonuclearleukocytes(PMN)monocytes/macrophages

Naturalkiller(NK)cell

Complementandacutephaseproteins

IntroductionTheprincipalmechanismsofinnateandadaptiveimmunityInnateimmunitymechanismofrecognitionPathogenassociatedmoleculespatterns(PAMPs）:LPS,DNA,RNA,ProteinDanger-associatedmolecularpatterns(DAMPS):DNA,HSPPatternrecognitionreceptors(PRR):

Toll-likereceptor(TLR),C-lectinrecptor(CLR),RIG-I-Likerecptor(RLR),NOD-likeReceptor(NLR)Toll-likereceptor(TLR)TLRManydifferenttypesofbloodcellsparticipateintheimmuneresponsetomicrobes:Innateimmunecells:“phagocytes”macrophage,neutrophils,dendriticcellsAdaptiveimmunecells:“l(fā)ymphocytes”Tcells,Bcells,APCInnateimmuneresponseIntroduction(Lung)MacrophageAttackingE.coli

InnateimmuneresponseIntroductionMacrophageAttackingE.coliAlthoughinnateimmunitycaneffectivelycombatmanyinfections,microbesthatpathogenicforhumanhaveevolvedtoresistinnateimmunity.Defenseagainsttheseinfectionsarethetaskoftheadaptiveimmuneresponse,andthisiswhydefectsintheadaptiveimmunesystemresultinincreasedsusceptibilitytoinfections.AdaptiveimmuneresponseAdaptiveimmuneresponseTheTcellsandBcellsinthebodyrecognizetheantigenand,inturn,becomeactivated.Theactivatedlymphocytesthenproliferateandcarryouttheirspecificeffectorfunctions.TypesofadaptiveimmunityTwotypesofadaptiveimmunityHumoralimmunity:mediatedbyBcellsanddefenseagainstextracellularmicrobes.Cell-mediatedimmunity:mediatedbyTcellsanddefenseagainstintracellularmicrobes.Cell-mediatedimmunity: Phagocytosis(cellulareating) cytotoxcity細(xì)胞毒性(cellularkilling)Humoralimmunity: antibodies:(alsocalledimmunoglobulin)proteinssecretedbyBcellsthatbinddirectlyandspecificallytopathogens.Antibodiestargetpathogensbymarkingthemfordestructionbyothercomponentsoftheimmunesystem.complement:groupofserumproteinsthatcandirectlykillpathogens.ImmuneEffectorMechanisms?2005ElsevierTypesofadaptiveimmunity.AdaptiveimmuneresponseIntroduction1.Theactivationoflymphocytes

antigeninteractswithspecificreceptors:Bcell---BCR(Bcellreceptor):membraneIgTcell---TCR(Tcellreceptor),co-stimulatorysignal2.Proliferationanddifferentiationoflymphocytes

Bcell----cytokines(IL-4,etc.)Tcell----Antigen-TCR;co-stimulatorysignal;cytokines(IL-2,IL-7,IL-15)3.Effectorcellsandtheirfunctions

Bcell----Antibody;Tcell----Th,CTL4.MemorycellsAdaptiveimmuneresponseIntroductionBCR(mIg)TCRαβThetwo-signalrequirementforlymphocyteactivation.Signal1isprovidedbyantigenrecognition.Signal2isprovidedbycomponentsofthemicrobesorsubstancesproducedduringtheinnateimmuneresponse.AdaptiveimmuneresponseIntroduction1.Theactivationoflymphocytes

antigeninteractswithspecificreceptors:Bcell---BCR(Bcellreceptor):membraneIgTcell---TCR(Tcellreceptor),co-stimulatorysignal2.Proliferationanddifferentiationoflymphocytes

Bcell----cytokines細(xì)胞因子(IL-4,etc.)Tcell----Antigen-TCR;co-stimulatorysignal共刺激信號;cytokines(IL-2,IL-7,IL-15)3.Effectorcellsandtheirfunctions

Bcell----Antibody;Tcell----CTL,Th4.MemorycellsDownloadedfrom:StudentConsult(on31May200605:26PM)?2005ElsevierDownloadedfrom:StudentConsult(on31May200605:26PM)?2005ElsevierLinksbetweeninnateandadaptiveimmunityTheinnateandadaptiveimmuneresponseIntroductionCharacteristicsCellsMoleculesInnateimmunityRespondsrapidlyNomemoryNoorlowspecificityPhysicalbarriersPhagocytes(PMNsandmacrophages)NaturalkillercellsHumoralfactorsComplementAcutephaseProteinsCytokinesAdaptiveimmunityRespondsSlowlyMemoryHighlyspecificTcellsBcellsDendriticcellsAntibodiesCytokinesGranzymesIndividualBandTcellspossesstheabilitytomakeaspecificreceptor(eachcellmakesadifferentreceptormolecule)AntigenbindstothecellsurfacereceptorandactivatesthecellProcesstakesseveraldays.Effectorcellsandmemorycellsareproduced.Memorycellscanthusbeactivatedfaster.ClonalselectiontheoryFrankM.BurnetTheclonalselectionhypothesisTheNobelPrizeinPhysiologyorMedicine1987"forhisdiscoveryofthegeneticprincipleforgenerationofantibodydiversity"SusumuTonegawa（利川根進）

ThegenesencodingtheantigenreceptorsofTandBcellsareassembledbyDNArearrangementasthesecellsdevelop.AsaresultofV(D)Jrecombination,everyBandTcellsexpressesauniqueversionoftheantigenreceptor.GenerearrangementofIgIntroductionConceptofImmunityImmuneResponseImmuneCellsTissuesandOrgansoftheImmuneSystemImmunopathologyBriefhistoryofImmuneResponseImmuneCellsIntroductionhematopoieticstemcell(HSC)Myeloidprogenitor髓系祖細(xì)胞LymphoidprogenitorGranulocytes(eosinophils嗜酸,neutrophils中性,basophils嗜堿)

Monocytes,macrophagesDendriticcellErythrocyte紅細(xì)胞Megakaryocyte巨核細(xì)胞TlymphocyteBlymphocyteNKcellDendriticcellMostbloodcellsacttofightinfection.AdaptiveimmunityInnateimmunityBloodcellslineages.1.Lymphocytes(exceptNKcells)arewhollyresponsibleforthespecificimmunerecognitionofpathogens,sotheyinitiateadaptiveimmuneresponses.2.Lymphocytesarederivedfrombone-marrowstemcells.3.Blymphocytesdevelopinthebonemarrow.Tlymphocytesdevelopinthethymus.IntroductionLymphocytesLymphocytesareextremelyheterogeneousinlineage,functionandphenotypeandarecapableofcomplexbiologicresponsesandactivities.Lymphocytesareoftendistinguishedbysurfaceproteinsthatmaybeidentifiedbypanelsofmonoclonalantibodies單克隆抗體.Thestandardnomenclature術(shù)語fortheseproteinsisthe“CD”(clusterofdifferentiation)numericaldesignation.

BLymphocytes⑴BCR:asurfacereceptor(mIg)specificforaparticularantigen⑵Bcellsplasmacellsantibody(thesamespecificityastheBCR)⑶humoralimmunityIntroductionAgsecrete

BLymphocytesIntroductionTCR:T-cellantigenreceptorTCR

+>95%

TCR

+1–5%1.CytotoxicTcells(CTL)2.helperTcells:Th1,Th2,Th173.RegulatoryTcells(Treg)andsuppressorTcells(Ts)IntroductionTLymphocytesPropertiesofTH1,TH2,andTH17subsetsofCD4+helperTcells.IntroductionTLymphocytes

TlymphocyteIntroduction

TLymphocytesHumanT-lymphocyteAttackingFibroblastTumorCellsSpecializedcellsthatdisplayantigenstoTcellsandprovidesecondsignal.ProfessionalAPCsincludedendriticcells(DCs),macrophages(M

)andBcells.Antigenpresentingcells(APC)Macrophage:powerfulinantigenprocessinganddestruction,butlowinantigenpresentation.Dendriticcells(DC):suchasLangerhanscell(LC),powerfulinantigenprocessingandpresentation.IntroductionAntigenpresentingcellsIntroductionNaturalkillercells(NK)1.10-15%ofbloodlymphocytes,LGL2.expressneitherT-cellnorB-cellantigenreceptorsIntroductionPhagocyticcellsMonocytes(blood)/Macrophages(tissues)

functions:1.removeparticulateantigens2.takeup,processandpresentantigenicpeptidestoTcellsdistribution:KupffercellsinthelivermicroglialcellsinthebrainIntroductionPhagocyticcellsPolymorphonucleargranulocytes

1.neutrophils;basophils;eosinophils2.neutrophilsareshort-livedphagocyticcells

multilobednucleus;10-20

m3.neutrophilshavealargearsenalofantibioticproteinsgranules:lysosomes;lactoferrinIntroductionPhagocyticcellsIntroductionPhagocyticcellsIntroductionmonocyteneutrophilPhagocyticcellsIntroductioneosinophilneutrophilPhagocyticcellsIntroduction

neutrophilactivatederythrocyteplateletIntroductionConceptofImmunityImmuneResponseImmuneCellsTissuesandOrgansoftheImmuneSystemImmunopathologyBriefhistoryofImmuneResponseTissuesoftheimmunesystemPrimary(orcentral)lymphoidorgansthebonemarrowthethymusSecondary(orperipheral)lymphoidorgansthespleenlymphnodesCutaneousandmucosalimmunesystemIntroductionGenerativelymphoidorgans:theorgansinwhichTandBlymphocytesmatureandbecomecompetenttorespondtoantigens.Peripherallymphoidorgans:theorgansinwhichadaptiveimmuneresponsestoforeignantigens(suchasmicrobes)areinitiated.Maturationoflymphocytes.Maturelymphocytesleavethegenerativelymphoidorgansandentercirculationandtheperipherallymphoidorgans,wheretheyrespondtoforeignantigensandfromwheretheyrecirculateinthebloodandlymph.

theplaceinwhichproliferationofHSCtakesplacetheplaceinwhichdevelopmentandmaturationofBcellsoccurThelymphoidprogenitorcellsaretransportedbycirculatingbloodtothethymusanddifferentiateintofunctionalTlymphocytesIntroductionBonemarrowThethymus1.Cells:thymicstromalcells(TSC)epithelialcells,monocytes(macrophage),TDCthymocytesTcell(

+)2.Structure:cortex---immaturethymocytesmedulla---maturethymocytesM

,TDC3.Function:ItisthesiteofTcellmaturation/selection;

ItdeterminesthespecificityoftheTCRexpressedontheTcellsreleasedtoperiphery

IntroductionThelymphnodeHuman:2-10mmindiameterroundandkidneyshapedConsistsof:cortex(B-cellarea)paracortex(T-cellarea)centralmedulla(B-cellarea)IntroductionThelymphnodeIntroductionDownloadedfrom:StudentConsult(on1June200602:08PM)?2005ElsevierThemorphologyoflymphnodes.Thestructuralorganizationandbloodflowinalymphnode.Lightmicrographshowsacross-sectionofalymphnodewithnumerousfolliclesinthecortex,someofthemcontaingerminalcenters,andthecentralmedulla.180-250ggerminalcenter(B)1.thewhitepulpperiarteriallymphaticsheath(T)

theredpulp(B)

2.function:

destroytheAg,agedplatelets

immuneresponseIntroductionThespleenIntroductionThespleenDownloadedfrom:StudentConsult(on1June200602:08PM)?2005ElsevierThemorphologyofthespleen.Asplenicarteriolesurroundedbytheperiarteriolarlymphoidsheath(PALS)andtheattachedfolliclecontainingaprominentgermianlcenter.LightmicrographofasectionshowsanarteriolewiththePALSandasecondaryfollicle.Withintheperipherallymphoidorgans,TcellsandBcellsaresegregatedintodifferentanatomiccompartments.Downloadedfrom:StudentConsult(on31May200605:26PM)?2005ElsevierSegregationofTandBcellsindifferentregionsofperipherallymphoidorgans.Thepathbywhichna?veTandBcellsmigratetodifferentareasofalymphnode.ImmunofluorescenceshowsthattheBcellsandTcellslocateinthefolliclesandintheparafollicularcortex,respectively.Mucosalimmunesystem(MIS)

1.non-encapsulatedlymphoidtissueinthelaminapropriaandsubmucosalareasofthegastrointestinal,respiratoryandgenitourinarytracts.2.tonsil,appendix,Peyer’spatches3.BcellIgAIEL

(intraepitheliallymphocytes)Adaptiveimmune(Tcells)4.function:local(mucosal)immunityIntroductionMucosal-associatedlymphoidtissue(MALT)McellsandProductionofIgAMcells:epithelialcellslackingthemicrovilli,havingadeeppocketinthebasolateralplasmamembraneLymphocyterecirculationLymphocytesleavethebloodviahigh-walledendotheliumofthepost-capillaryvenules.Lymphocytetraffickingexposesantigentoalargenumberoflymphocytes.Introduction

LymphocyterecirculationIntroductionRecirculationofTcells.NaiveTcellsmigratefrombloodthroughHEVintotheTcellareasofalymphnode,whereTcellsareactivatedbyantigens.ActivatedTcellsexitthelymphnode,enterbloodstream,andmigratepreferentiallytoperipheraltissuesatsitesofinfectionandinflammation,whereinfectiousmicrobesareeliminated.IntroductionConceptofImmunityImmuneResponseImmuneCellsTissuesandOrgansoftheImmuneSystemImmunopathologyBriefhistoryofImmuneResponseImmunopathology

Hypersensitivity-overactiveimmuneresponseImmunodeficiency-ineffectiveimmuneresponseAutoimmunity-inappropriatereactiontoselfantigensCancerIntroductionConceptofImmunityImmuneResponseImmuneCellsTissuesandOrgansoftheImmuneSystemImmunopathologyBriefhistoryofImmuneResponse

BriefHistoryofImmunology1.EmpiricalImmunology(AD1700-1900)2.ScientificImmunology(1900-1950s)3.ModernImmunology(1960s-Present)DocumentsshowthatasearlyasAD1000,theancientChinesecustomexistedofhavingchildreninhalepowdersmadefromthecrustyskinlesionsofpatientsrecoveringfromsmallpoxEdwardJenner(1749-1823)JennervaccinationAliMaaliWhyCanweeradicatethesmallpox??Noanimalreservoir?Lifelongimmunity?Subclinicalcasesrare?Oneserotype?Effectivevaccine?MajorcommitmentbygovernmentsLouisPasteur

Fowlcholera1879

Pasteurellamultocida狂犬病疫苗炭疽病疫苗ScientificImmunologyTheNobelPrizeinPhysiologyorMedicine1901EmilvonBehring"forhisworkonserumtherapy,especiallyitsapplicationagainstdiphtheria,bywhichhehasopenedanewroadinthedomainofmedicalscienceandtherebyplacedinthehandsofthephysicianavictoriousweaponagainstillnessanddeaths".TheNobelPrizeinPhysiologyorMedicine1905RobertKoch"forhisinvestigationsanddiscoveriesinrelationtotuberculosis".TheNobelPrizeinPhysiologyorMedicine1908IlyaIlyichMechnikovandPaulEhrlich"inrecognitionoftheirworkonimmunity"免疫學(xué)系統(tǒng)復(fù)雜，常通過多個機制行使功能：俄國科學(xué)家Mechnikov識別出了能吞噬入侵細(xì)胞的巨噬細(xì)胞，而Ehrlich則提出了側(cè)鏈理論，指出了對抗入侵者時，血液中的抗體是如何釋放出來的。TheNobelPrizeinPhysiologyorMedicine1913CharlesRichet"inrecognitionofhisworkonanaphylaxis".TheNobelPrizeinPhysiologyorMedicine1930TheNobelPrizeinPhysiologyorMedicine1930wasawardedtoKarlLandsteiner"forhisdiscoveryofhumanbloodgroups".SirFrankMacfarlaneBurnetandPeterBrianMedawar"fordiscoveryofacquiredimmunologicaltoleranceTheNobelPrizeinPhysiologyorMedicine1960TheNobelPrizeinPhysiologyorMedicine1972GeraldM.EdelmanandRodneyR.Porter"fortheirdiscoveriesconcerningthechemicalstructureofantibodies"TheNobelPrizeinPhysiologyorMedicine1980BarujBenacerraf,JeanDaussetandGeorgeD.Snelland"fortheirdiscoveriesconcerninggeneticallydeterminedstructuresonthecellsurfacethatregulateimmunologicalreactions".TheNobelPrizeinPhysiologyorMedicine1984NielsK.Jerne,GeorgesJ.F.K?hlerandCésarMilstein"fortheoriesconcerningthespecificityindevelopmentandcontroloftheimmunesystemandthediscoveryoftheprincipleforproductionofmonoclonalantibodies".TheNobelPrizeinPhysiologyorMedicine1996SusumuTonegawa"forhisdiscoveryofthegeneticprincipleforgenerationofantibodydiversity".TheNobelPrizeinPhysiologyorMedicine1996PeterC.DohertyandRolfM.Zinkernagel"fortheirdiscoveriesconcerningthespecificityofthecellmediatedimmunedefence"TheNobelPrizeinPhysiologyorMedicine2011wasdivided,onehalfjointlytoBruceA.BeutlerandJulesA.Hoffmann"fortheirdiscoveriesconcerningtheactivationofinnateimmunity"

andtheotherhalftoRalphM.Steinman"forhisdiscoveryofthedendriticcellanditsroleinadaptiveimmunity".TheNobelPrizeinPhysiologyorMedicine2011Thankyou!Antigen（Ag）ChapterⅡAntigen1.Concept2.Immunogenicityandspecificity3.Requirementsforimmunogenicity4.Typesofantigens5.SuperantigenandadjuvantsKNOWLEDGEPOINTSConcept1.抗原Antigen(Ag)–

thesubstancesthatarerecognizedbyTCR/BCRorantibodyandinduceaspecificimmuneresponse.

蛋白質(zhì)、多糖、脂類、核酸Antigen2.PropertiesofAg-⑴immunogenicity-⑵immunoreactivity(reactwiththeproductsofaspecificimmuneresponse)AgTBT漿細(xì)胞致敏T細(xì)胞抗體免疫原性AgTBT漿細(xì)胞致敏T細(xì)胞免疫反應(yīng)性抗體

-substancesthatinducespecificimmuneresponse.CompleteAgs（完全抗原）：havethepropertiesofimmunogenicityandimmunoreactivity.Hapten（半抗原）：havethepropertyofimmunoreactivitybutnotimmunogenicity.

-Asubstancethatisnon-immunogenicbutwhichcanreactwiththeproductsofaspecificimmuneresponse.Antigen

Haptensaresmallmoleculeswhichcouldneverinduceanimmuneresponsewhenadministeredbythemselvesbutwhichcanwhencoupledtoacarriermolecule.

hapten+carrier→completeAgAntigen抗原特異性Antigenspecificityinduceaspecificimmuneresponse,reactwiththeproductsofaspecificimmuneresponseAntigenicspecificity抗原特異性

1.epitope(antigenicdeterminant)

抗原決定簇（基），表位-theportionoftheantigenthatbindsspecificallywiththebindingsiteofanantibodyorareceptoronalymphocyte.-thesizeofanepitopeisapproximatelyequivalentto5-15aminoacids.抗原結(jié)合價antigenicvalence

AntigenEpitope表位AntigendescriptionexampleOneepitopehaptensManyepitopesofthesamespecificityManypolysaccharides,homopolymersManyepitopesofdifferentspecificityproteinsRepresentationofsomepossibleantigenicstructures2.thetypesofepitope

▲conformationalepitope構(gòu)象表位:

Someepitopesformonlywhenthecriticalresiduesarebroughttogetherinspacethroughfoldingofthepolypeptideorpolysaccharidechainintoitsnormalthree-dimensionalconformation.▲sequentialepitope順序或線性表位:

Alloftheaminoacidorsugarresiduesthatformagivenepitopearepositionedsequentiallyinthelinearsequenceofaproteinorpolysaccharideantigen.AntigenBindingsiteforantigenBindingsiteforantigen構(gòu)象表位線性表位

★Bcellepitope★TcellepitopeAntigenAntigen

TcellepitopeBcellepitope●ReceptorTCRBCR●APC,MHCnecessaryunnecessary●Characterlinearshortnaturalpolypeptidepeptidepolysaccharideslineardeterminantconformationaldeterminant;lineardeterminant

●Size8-10aa(CD4+T)5-15aa2,9anchorresidue13-17aa(CD8+T)●LocationAgsurfaceofAg

Antigen3.hapten-carriereffect半抗原載體效應(yīng)AntigenAntigencommonepitopeandcross-reaction（交叉反應(yīng)）crossantigenFactorsinfluencingimmunogenicityContributionoftheantigen1.Foreignnessy異物性

-Theimmunesystemnormallydiscriminatesbetweenselfandnon-selfsuchthatonlyforeignmoleculesareimmunogenic.AntigenFactorsinfluencingimmunogenicity2.chemicalComposition–

proteinpolysaccharidenuclearacid3.size-Thereisnotabsolutesizeabovewhichasubstancewillbeimmunogenic.Ingeneral,thelargerthemoleculethemoreimmunogenicitislikelytobe.Antigen4.chemicalcomplexity-Ingeneral,themorecomplexthesubstanceischemicallythemoreimmunogenicitwillbe.Anincreaseinthechemicalcomplexityofacompoundisaccompaniedbyanincreaseinitsimmunogenicity5.conformation

化學(xué)基團的性質(zhì)、數(shù)目、位置和空間構(gòu)象6.accessibility

7.physicalform

-Ingeneralparticulateantigensaremoreimmunogenicthansolubleones.AntigenAntigenB.Contributionofthehost1.GeneticFactors-Somesubstancesareimmunogenicinonespeciesbutnotinanother.Similarly,somesubstancesareimmunogenicinoneindividualbutnotinothers(i.e.respondersandnon-responders).2.Age，gender

-Agecanalsoinfluenceimmunogenicity.Usuallytheveryyoungandtheveryoldhaveadiminishedabilitytomountandimmuneresponseinresponsetoanimmunogen.AntigenC.

MethodofAdministration1.Dose-Thedoseofadministrationofanimmunogencaninfluenceitsimmunogenicity.2.Route-Generallythesubcutaneousrouteisbetterthantheintravenousorintragastricroutes.Therouteofantigenadministrationcanalsoalterthenatureoftheresponse3.AdjuvantsAntigenTypesofantigens抗原的種類Th:Thymus-dependentantigen(TD-Ag)Thymus-independentantigen(TI-Ag)Relative:XenogenicantigenAllogenicantigenAutoantigenHeterophilicantigenIdiotypicantigenAntigenTD-Ag胸腺依賴性抗原Thymus

-dependentantigensarethosethatdonotdirectlystimulatetheproductionofantibodywithoutthehelpofTcells.Bcellepitope＋TcellepitopeHumoralimmunityandcellularimmunityAntibody:fivetypesImmunememoryProteinsarethymus-dependentantigens.AntigenTI-Ag胸腺非依賴性抗原Thymus-independentantigensareantigenswhichcandirectlystimulatetheBcellstoproduceantibodywithouttherequirementforTcellhelpIngeneral.onlyBcellepitopeHumoralimmunityAntibody:IgMNoImmunememorypolysaccharidesareTI-antigens.AntigenTI-Ag

Thymus-independentantigenscanbesubdividedintoType1andType2basedontheirabilitytopolyclonallyactivateBcells.

Type1TI-Ag(LPS)arepolyclonalactivatorswhileType2arenot.Antigen異嗜性抗原HeterophilicAg(Forssmanantigen)-Across-reactingantigenthatappearsinwidelyrangingspeciessuchashumansandbacteria.Postinfectiousglomerulonephritis:groupAStreptococcusglomerularbasementmembraneAntigenTypesofantigensForssmanantigen豚鼠免疫家兔肝、脾、腎

等組織乳劑分離血清與豚鼠組織發(fā)生反應(yīng)結(jié)合綿羊紅細(xì)胞HeterophilicAg(Forssmanantigen)XenogenicAg異種抗原-Anantigenfoundinmorethanonespecies.AllogenicAg同種異型抗原-individualsofaspeciesdifferinalleles(areallogeneic)andtheantigenicdifferenceswillcauseanimmuneresponsetoallografts.TheantigensconcernedareoftenoftheMHCandarereferredtoasalloantigens.AntigenAutoantigen自身抗原-Theantigensofanorganismsowncellsandcellproductsareselfantigenstotheimmunesystemofthatorganism.-Clonesofimmunecellsreactivewithselfantigensarenormallyeliminated.AntigenTypesofantigensidiotypicAg獨特型抗原-Thecombinedantigenicdeterminants(idiotopes)foundonantibodiesofanindividualthataredirectedataparticularantigen;suchantigenicdeterminantsarefoundonlyinthevariableregion.AntigenEndogenousantigen內(nèi)源性

Exogenousantigen外源性Tolerogen,allergen耐受原Tolerogen:anantigenthatinducesastateofspecificimmunologicalunresponsiveness變應(yīng)原Allergen:asubstancecapableofinducingallergyorspecifichypersensitivity.pollens,dust