固有及获得性免疫基础.ppt

ElementsofInnateandacquiredImmunity,Innate(nonspecific)ImmunityPhysiologicalandChemicalBarriersSkinandmucousmembranesAcidpHFattyacidsHydrolyticenzymes(lysozyme)ProteolyticenzyemsandbileInterferonsproteinsmadebycellsinresponsetovirusinfectionthatinducedageneralizedantiviralstateinsurroundingcellsComplementsystem20proteinsinacontrolledenzymaticcascadewhichtargetsthemembraneofpathogenicorganismsandtargetsthemefordestruction,InnateImmunityCellularDefenses,PhagocytosisandExtracellularKillinginternalizationofforeignmacromoleculesandcellsEndocytosisprocesswherebymacromoleculespresentintheextracellulartissuefliudareingestedbycellsPinocytosisnonspecificmembraneinvaginationReceptor-mediatedendocytosisselectivebindingofmacromoleculestospecificmembranerecptorsEndosomes(acidic)+Lysosomes(nucleases,lipases,proteases)secondarylysosomesforbreakdown,InnateImmunityCellularDefenses,Phagocytosisingestionanddestructionbyindividualcellsofinvadingforeignparticles(bacteria)OpsoninsfactorsthatenhancephagocytosisoftheparticlePhagosome+Lysosomedigestparticle,PhagocyticCells,Polymorphonuclearleukocytes(PMN)MacrophagesPhagocyticmonocytesFixedmacrophagesofthereticuloendothelialsystemAllthesecellsreleasecytokinesuponactivation,PhagocyticCells,Polymorphonuclearleukocytes(PMN)GranulocytesIncludebasophils,mastcells,eosinophils,neutrophilsShort-livedphagocyticcellsthatcontainlysosomesProduceperoxideandsuperoxideradicalsBactericidalproteinslactoferrinPMNsplayamajorroleinprotectiona/ginfectionDefectschronicorrecurrentinfection,PhagocyticCells,MacrophagesphagocytesderivedfrombloodmonocytesMigrationfrombloodtotissuesdifferentiationKupffercellsintheliverAlveolarmacrophagesinthelungSplenicmacrophagesinthewhitepulpPeritonealmacrophagesfreefloatinginperitonealfluidMicroglialcellsintheCNS,PhagocyticCells,ReticuloendothelialSystem(RES)IncludeseachofthesemacrophagepopulationsWidelydistributedthroughoutthebodyusuallylocatedalongcapillariesPhagocytizemicroorganimsandforeignsubstancesinbloodstreamandtissuesDestructionofagedandimperfectcellssuchasRBC,PhagocyticCells,CellsofthemacrophageserieshavetwomajorfunctionsEngulfanddigestmicroorganismsandforeignparticlesAntigenpresentationTakeupAgandprocessforpresentationtoTcellsOtherAgpresentingcells(hematopoieticprecursor,notveryphagoctic)DendriticcellsinspleenandlymphnodesInterdigitatingcellsofthethymusLangerhanscellsintheskin,CellularDefenses,MonocytescentralroleininnateimmunityKeyroleinafferent(induction)limboftheacquiredimmuneresponsebyinitiatingTcellresponsesMacrophagesroleinefferentoreffectorlimboftheacquiredimmuneresponseastheendcellsthatbecomeactivatedbyT-cellreleasedcytokinesthatenhancekillingofpathogens,InnateCellularDefenses,ExtracellularKillingNaturalKillerCellscomponentoftheinnateimmunesystemSimilarfunctionascytotoxicTcellsofacquiredimmunesystemRecognize“altered”featuresofthemembranesofabnormalcells(virus-infectedorcancercells)Destroytargetcellsbyreleaseofbiologicallypotentmoleculesthatkilltargetcellwithinaveryshorttime,ExtracellularKilling,NaturalKiller(NK)cellsRoleinearlyviralinfectionortumorogenesisbeforeactivationofacquiredimmunityLargegranularlymphocytesAbletolysewithoutpriorstimulationLackAgspecificreceptorsKiller-cellinhibitoryreceptors(KIR)bindtoClassIMHCBycell-cellcontactcandetermineifapotentialtargethaslostitsselfAg(MHC)Infectedortransformed(tumor)cellshavereducedClassIMHContheirsurfacefailtoengageKIRandbecomesusceptibletoNKcellmediatedcytotoxicity,NaturalKiller(NK)Cells,KillingisachievedbythereleaseofCytotoxicmoleculesthatcauseporesinthetargetcellsleadingtolysisOthermoleculesentertargetcellandinduceapoptosis(programmedcelldeath)byenhancedfragmentationofthetargetcellsnuclearDNAKillingisenhancedbyIL-2,IL-12andinterferons,Inflammation,MajorcomponentofinnateandacquireddefenseInvolvesphagocytosisandmediatorsexceretedbyphagocyticcellsInitiatedbytissuedamageMechanical(e.g.burn)Chemical(e.g.exposuretocorrosivechemical)Biological(e.g.infectionbymicroorganims)Immunologicinjury(e.g.hypersensitivity)Protectiveresponsetoinjurytorestorenormalstate,HallmarkSignsofInflammation,Swelling(tumor)Redness(rubor)Heat(calor)Pain(dolor)LossoffunctiontotheareaOccurwithinminutesafterinjurythroughactivationandincreasedconcentrationofacute-phaseproteinsLocalizedInflammatoryResponsesActivationofclottingKinin-formingpathwaysFibrolyticpathways,Kininshaveseveralimportanteffects:,ActdirectlyonlocalsmoothmuscleandcausemusclecontractionActonexonstoblocknervousimpulses,leadingtodistalmusclerelaxationMostimportantly,theyactonvascularendothelialcells,causingthemtocontract,leadingtoincreaeinvascularpermeability,andtoexpressendothelialcelladhesionmolecules(ECAMs)leadingtoleukocyteadhesionandextravasation.Verypotentnervestimulatorsandarethemoleculesmostresponsibleforpain(anditching).Kininsarerapidlyinactivatedbyproteasesthataregeneratedduringthelocalizedrepsonse.,SystemicInflammatoryResponse,InductionoffeverCausedbymanybacterialproducts(endotoxinsfromG(-)bacteria)Endogenouspyrogensfrommonocytesandmacrophages(IL-1andcertaininterferons)IncreasedWBCproductionIncreasedsysnthesisofhydrocortisoneandadrenocorticotropichormone(ACTH)ProductionofacutephaseproteinsC-reactiveproteinbindstomembranesofcertainmicroorganismstoactivatethecomplementsystem,CytokinesplayakeyroleinInflammation,IL-1,IL-6andtumornecrosisfactora(TNF-a)ReleasedbyactivatedmacrophagesInduceadhesionmoleculesonthewallsofvascularendothelialcellstowhichneutrophils,monocytesandlymphocytesadherebeforemovingoutofthevessel(extravasation)toaffectedtissueInducecoagulationandvascularpermeabilityIncreasedchemotaxisforleukocytesandincreasedphagoctosis(IL-8andinterferon-g)Alltheseeffectsresultinaccumulationoffluid(edema)andleukocyticcellsintheinjuredarea.Amplifyresponsebytransportingotherbiologicallyactivecompoundstositeandaccumulatedcellsattractingandactivatingmorecells,OtherBiologicallyActivatedSubstances,DegradativeenzymesToxicfreeradicalsAcidsGrowthinhibitorsAcutephaseproteinsInterferonsHarmfultomicroorganinsInfluencedbyage,raceandhormonalandmetabolicstatus,Mostcellsinvolvedininflammationarephagocyticcel