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 blood fetusbarrier 二 Cellsinvolvedininnateimmunityandtheirfunctions PhagocuteNaturalkillercells TcellsNKTcellsB1cells 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 CD14C3bRFc RToll 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 peroxidate Localinflammatoryreaction 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 KARKARrecognizecellcarbohydrateligands ITAM transduceactivationsignalsKIRTheextracellularregionofKIRrecognizeMHC Iofselfcells ITIM transduceinhibitorysignalsRegulationofNKcellkillingeffectbytworeceptors 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 Thesamegroupofcellsexpressonlyonekindof TCR samespecificityofantigenrecognition responsetocommonantigenBiologicalFunction 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 laminapropriaofbowels wallsFeatures appearearlyintheontogenesis self renewalSurfacemarkers CD5 CD11 mIgM CD23 MolecularrecognitionNarrowspectrumofantigenrecognition 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 CommonlyspecificforpathogensRequiredforthemicrobes survivalandpathogenicityMolecularbasisforthepan 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 Innateimmuneresponseinitializesadaptiveimmuneresponse Innateimmuneresponseinfluencesthetypeofadaptiveimmuneresponse Innateimmuneresponseassistsadaptiveimmuneresponse Non specificimmunityspecificimmunity Cellsinvolved epitheliummucosalcells phagocyte NK NK1 1 T B 1B T T B APC phase instant 96hafter96h features non specific broadspectrumofantigenrecognition totakeeffectwithoutrequirementofclonalexpansionanddifferentiation specific exclusiveantigenrecognition totakeeffectwithrequirementofclonalexpansionanddifferentiation duration noimmunologicalmemory shortduration Withimmunologicalmemory longduration BiologicalsignificancesofinnateimmunityParticipatingandregulatingtheinitiationofadaptiveimmuneresponseAffectingthestrengthofadaptiveimmuneresponseAffectingthetypeofadaptiveimmuneresponseAffectingBcellmemory negativeselection selftolerance TomastercelltypesparticipatingtheinnateimmuneresponseTomasterthesignificanceofpatternrecognitionmoleculesandpathogenassociatedmoleculesTomasterKAR KIRandtheirmodulationtoNKcellkillingeffectTomasterthemainfeaturesofadaptiveimmunityandinnateimmunityTobefamiliarwiththekindsofphagocytesandthebiologicalfunctionTobefamiliarwith TcellandB 1BcellandtheirfunctionTounderstandfunctionoftheepithelialcellsandtheirattachmentsTounderstandthecharacteristicsofvariousphagocytes