固有免疫细胞及功能英.ppt

,Cellsininnateimmunityandtheirfunctions,一.Tissue,cellsandmoleculesoftheinnateimmunesystemPhasesofinnateimmuneresponsesCharacteristicsofinnateimmuneresponseanditsrelationshipwithadaptiveimmuneresponse,SectionITissue,cellsandmoleculesoftheinnateimmunesystem,AcquiredImmunityAdaptiveImmunitySpecificImmunity,InnateImmunityNativeImmunityNonspecificImmunity,Speciesdevelopment,formedevolutionallyPossessfromthetimeofbirth，reactrapidlyNon-specificanti-infectionimmunity,alsoinvolvedinspecificimmunity,一.Tissuebarriersandtheireffection,（一）TheskinandmucosalsurfacesprovideprotectivebarriersagainstinfectionPhysicalbarriers:epithelial,cilia,mucusChemicalbarriers:lacticacid,unsaturatedfattyacid,gastricacidBiologicalbarriers:microorganisms,（二）Blood-brainbarrier（三）bloodfetusbarrier,二.Cellsinvolvedininnateimmunityandtheirfunctions,PhagocuteNaturalkillercellsTcellsNKTcellsB1cells,1.phagocytes,Mononuclearphagocytesystem,neutrophils,monocyte,macrophage,microglialcells,Kupffer,Osteoclast,MacrophageLong-lived(uptoseveralmonths)Large,pleomorphismandrichinlysosomesinthecytoplasm.MHC-I/IIandmanyadhensionmoleculesManyreceptors,NeutrophilShort-livedSmallandroundLargequantities,replacedrapidlyLargeamountofazurophilgranuleandneutrophilgranuleinthecytoplasmMHC-Iandreceptorofadhensionmolecules,surfacereceptorsofphagocytesMannitol,fucose,phosphatidereceptorCR3,CR4,CD14C3bRFcRToll-likereceptorscavenger,RecognizedmoleculesCorrespondingcarbohydrateandphosphatideLPSAntigensentrappedbyC3bAntigensspeciallyboundbyIgGPAMP,PhagocytesBiologicalfunctions,PhagocytesBiologicalfunctionsAntimicrobialandcytotoxicactivityOxygen-dependent,Oxygen-independentSecretionoffactorsCytokines,InflammantorymediatorsAntigenpresentationIntrinsic,ExtrinsicAnti-tumour,Oxygen-dependentkillingmechanismsReactiveoxygenintermediates(ROIs)Neutrophilmyeloperoxidase(MPO)Reactivenitrogenintermediates(RNIs)Oxygen-dependentkillingmechanismsacidpH,lysozyme,lactoferrin,cationicprotein,elastase,Antimicrobialandcytotoxicactivity,SecretionoffactorsReleasedinappropriateorlargequantitiesCytokines：TNF-,IL-1,IL-6,IL-8,IL-12,MCP-1Inflammationmediators：prostaglandinE,LTB4,PAF,phosphatidase,peroxidateLocalinflammatoryreaction（TNF-、IL-1、LTB4）Feverandacutephasereaction（CRP、MBL）Immunoregulation（IL-1、IL-6、IL-12）,PhagocytesBiologicalfunctionsAnti-infectionAnti-tumor:directlycontactandfusewiththetumourcellmembrane;cytotoxicsubstance,proteinase,cytolysin,TNF-,ADCCmediatedbytumorspecificantibodyAntigenprocessingandpresentationImmunoregulation,PBMC,SpleenLargeamountofazurophilgranuleinthecytoplasmaKillthetargetcellsdirectlywithnoneedsofpreactivationsurfacemarkers:CD3-,CD56,CD16,2.NKCells,NKcells,Molecularrecognition:killeractivatoryreceptor(KAR)killerinhibitoryreceptor(KIR)KARKARrecognizecellcarbohydrateligandsITAMtransduceactivationsignalsKIRTheextracellularregionofKIRrecognizeMHC-IofselfcellsITIMtransduceinhibitorysignalsRegulationofNKcellkillingeffectbytworeceptors,NKcellsBiologicalFunctionsAnti-infection：lysis,IFN-andTNF-Anti-tumor：directlycontactandfusewithtumourcellsmembraneADCCmediatedbytumorspecificantibodiesImmunoregulation,3.TcellDistributions:epithelia,mucosasurfacemarkers:TCR,CD2/3/16/25/45,LFA-1，DNMolecularrecognition:Narrowspectrumofantigenrecognition：HSP,CD1complex,viralproteins(VP)ThesamegroupofcellsexpressonlyonekindofTCR:samespecificityofantigenrecognitionresponsetocommonantigenBiologicalFunction:anti-infectioninskinandmucosa,anti-tumor,immunoregulation,4.NKTcellsDistribution:liver,bonemarrow,thymussurfacemarker:NK1.1,TCR-CD3complexmolecularrecognitionNarrowspectrumofantigenrecognition：CD1complex，withoutMHCrestrictionBiologicalfunction:anti-infection,anti-tumor,involvedinimmunoregulationbysecretingcytokines,5.B1cellDistribution:abdomen,thoraciccavity，laminapropriaofbowelswallsFeatures:appearearlyintheontogenesis，self-renewalSurfacemarkers:CD5、CD11、mIgM，CD23MolecularrecognitionNarrowspectrumofantigenrecognition：TI-2polysaccharideantigen,TI-1polysaccharideantigen（LPS）,self-antigenFeaturesofresponse,Othertypesofcellsinvolvedintheinnateimmunity:DendriticcellEosinophilgranulocyteBasophilicgranulocyteMastcell,三.Innateeffectormoleculesandtheirmainfunction,（一）complementsystem,（二）Cytokines1.Cytokinestoinduceanti-viralability2.CytokinestoinduceandpromoteInflammatoryreactions3.Cytokinestoinduceandenhanceanti-tumorabilities,（三）Defensin（四）Lysozyme（五）-Lysin,TransientphaseofinnateimmuneresponseEarlyphaseofinnateimmuneresponseInductionPhaseofadaptiveimmuneresponse,Section2Phasesofinnateimmuneresponse,Section3CharacteristicsofInnateImmuneResponseandItsRelationshipwithAdaptiveImmuneResponse,.Characteristicsofinnateimmuneresponse,（一）Recognitionfeaturesofinnateimmunecells1.Pattern-recognitionreceptors(PRRs)andpathogen-associatedmolecularpatterns(PAMPs),（1）Pattern-recognitionReceptors,PRRsExpressedonthesurfaceofinnateimmunecellswiththeabilityofrecognizingoneormorePAMPsLackofdiversity,non-clonalexpression,mediatingrapidbiologicalresponseMaintypes:Mannose-bindingreceptor,scavengerreceptor,Toll-likereceptorBiologicalfunctions:Opsonization,activationofcomplementsystem,phagocytosis,initializingcellactivationandtransductionofinflammatorysignal,inductionofapoptosis,(2)PathogenAssociatedMolecularPatterns,PAMPsSomenon-specificandhighlyconservedmolecularstructuressharedbyaclass/groupofspecifiedmicrobialpathogens,thatcanberecognizedbynon-specificimmunecells.Forexample:lipopolysaccharide(LPS),teichoicacid,peptidoglycan(PG),mannose,bacterialDNA/RNA.etal.Features:CommonlyspecificforpathogensRequiredforthemicrobessurvivalandpathogenicityMolecularbasisforthepan-specificrecognitionofthehost,2.SignaltransductionmediatedbyPRRs（TLRs）,MD2,TLR6,TLR2,TLR1,CD14,TLR4,TLR3,TLR5,TLR9,Peptidoglycan,Teichoicacid（G）BacteriumlipoproteinLPS（leptospire）CellwallsofMycobacteriumZymosan,LPS（G）teichoicacid（G）RSVFprotein,dsDNA,Flagellin,UnmethylatedCpGDNA,FeaturesofInnateImmuneCellResponseVariouschemokinereceptorsonthesurfaceDirectactivationintheinflammationsiteShort-lived,withoutmemory,RelationshipbetweenInnateImmuneReponseandAdaptiveImmuneResponse,InnateimmuneresponseinitializesadaptiveimmuneresponseInnateimmuneresponseinfluencesthetypeofadaptiveimmuneresponseInnateimmuneresponseassistsadaptiveimmuneresponse,Non-specificimmunityspecificimmunity,Cellsinvolved,epitheliummucosalcells,phagocyte,NK,NK1.1+T,B-1B,T,T,B,APC,phase,instant96hafter96h,features,non-specific,broadspectrumofantigenrecognition，totakeeffectwithoutrequirementofclonalexpansionanddifferentiation,specific，exclusiveantigenrecognition，totakeeffectwithrequirementofclonalexpansionanddifferentiation,duration,noimmunologicalmemory，shortduration,Withimm