固有及获得性免疫基础

固有及获得性免疫基础InnateImmunity–CellularDefensesPhagocytosisandExtracellularKilling–internalizationofforeignmacromoleculesandcellsEndocytosis–processwherebymacromoleculespresentintheextracellulartissuefliudareingestedbycellsPinocytosis–nonspecificmembraneinvaginationReceptor-mediatedendocytosis–selectivebindingofmacromoleculestospecificmembranerecptorsEndosomes(acidic)+Lysosomes(nucleases,lipases,proteases)secondarylysosomesforbreakdown

2020/12/102InnateImmunity–CellularDefensesPhagocytosis–ingestionanddestructionbyindividualcellsofinvadingforeignparticles(bacteria)Opsonins–factorsthatenhancephagocytosisoftheparticlePhagosome+Lysosomedigestparticle2020/12/103PhagocyticCellsPolymorphonuclearleukocytes(PMN)MacrophagesPhagocyticmonocytesFixedmacrophagesofthereticuloendothelialsystemAllthesecellsreleasecytokinesuponactivation2020/12/104PhagocyticCellsPolymorphonuclearleukocytes(PMN)GranulocytesInclude–basophils,mastcells,eosinophils,neutrophilsShort-livedphagocyticcellsthatcontainlysosomesProduceperoxideandsuperoxideradicalsBactericidalproteins–lactoferrinPMNsplayamajorroleinprotectiona/ginfectionDefects–chronicorrecurrentinfection2020/12/105PhagocyticCellsMacrophages–phagocytesderivedfrombloodmonocytesMigrationfrombloodtotissuesdifferentiationKupffercellsintheliverAlveolarmacrophagesinthelungSplenicmacrophagesinthewhitepulpPeritonealmacrophagesfreefloatinginperitonealfluidMicroglialcellsintheCNS2020/12/106PhagocyticCellsReticuloendothelialSystem(RES)IncludeseachofthesemacrophagepopulationsWidelydistributedthroughoutthebody–usuallylocatedalongcapillariesPhagocytizemicroorganimsandforeignsubstancesinbloodstreamandtissuesDestructionofagedandimperfectcellssuchasRBC2020/12/107PhagocyticCellsCellsofthemacrophageserieshavetwomajorfunctionsEngulfanddigestmicroorganismsandforeignparticlesAntigenpresentationTakeupAgandprocessforpresentationtoTcellsOtherAgpresentingcells(hematopoieticprecursor,notveryphagoctic)DendriticcellsinspleenandlymphnodesInterdigitatingcellsofthethymusLangerhanscellsintheskin2020/12/108CellularDefensesMonocytescentralroleininnateimmunityKeyroleinafferent(induction)limboftheacquiredimmuneresponsebyinitiatingTcellresponsesMacrophages–roleinefferentoreffectorlimboftheacquiredimmuneresponseastheendcellsthatbecomeactivatedbyT-cellreleasedcytokinesthatenhancekillingofpathogens2020/12/109InnateCellularDefensesExtracellularKillingNaturalKillerCells–componentoftheinnateimmunesystemSimilarfunctionascytotoxicTcellsofacquiredimmunesystemRecognize“altered”featuresofthemembranesofabnormalcells(virus-infectedorcancercells)Destroytargetcellsbyreleaseofbiologicallypotentmoleculesthatkilltargetcellwithinaveryshorttime2020/12/1010ExtracellularKillingNaturalKiller(NK)cellsRoleinearlyviralinfectionortumorogenesisbeforeactivationofacquiredimmunityLargegranularlymphocytesAbletolysewithoutpriorstimulationLackAgspecificreceptorsKiller-cellinhibitoryreceptors(KIR)bindtoClassIMHCBycell-cellcontactcandetermineifapotentialtargethaslostitsselfAg(MHC)Infectedortransformed(tumor)cellshavereducedClassIMHContheirsurface–failtoengageKIRandbecomesusceptibletoNKcellmediatedcytotoxicity2020/12/1011NaturalKiller(NK)CellsKillingisachievedbythereleaseofCytotoxicmoleculesthatcauseporesinthetargetcellsleadingtolysisOthermoleculesentertargetcellandinduceapoptosis(programmedcelldeath)byenhancedfragmentationofthetargetcellsnuclearDNAKillingisenhancedbyIL-2,IL-12andinterferons2020/12/1012InflammationMajorcomponentofinnateandacquireddefenseInvolvesphagocytosisandmediatorsexceretedbyphagocyticcellsInitiatedbytissuedamageMechanical(e.g.burn)Chemical(e.g.exposuretocorrosivechemical)Biological(e.g.infectionbymicroorganims)Immunologicinjury(e.g.hypersensitivity)Protectiveresponsetoinjurytorestorenormalstate2020/12/1013HallmarkSignsofInflammationSwelling(tumor)Redness(rubor)Heat(calor)Pain(dolor)LossoffunctiontotheareaOccurwithinminutesafterinjurythroughactivationandincreasedconcentrationofacute-phaseproteinsLocalizedInflammatoryResponsesActivationofclottingKinin-formingpathwaysFibrolyticpathways2020/12/1014Kininshaveseveralimportanteffects:ActdirectlyonlocalsmoothmuscleandcausemusclecontractionActonexonstoblocknervousimpulses,leadingtodistalmusclerelaxationMostimportantly,theyactonvascularendothelialcells,causingthemtocontract,leadingtoincreaeinvascularpermeability,andtoexpressendothelialcelladhesionmolecules(ECAMs)leadingtoleukocyteadhesionandextravasation.Verypotentnervestimulatorsandarethemoleculesmostresponsibleforpain(anditching).Kininsarerapidlyinactivatedbyproteasesthataregeneratedduringthelocalizedrepsonse.2020/12/1015SystemicInflammatoryResponseInductionoffever–Causedbymanybacterialproducts(endotoxinsfromG(-)bacteria)Endogenouspyrogensfrommonocytesandmacrophages(IL-1andcertaininterferons)IncreasedWBCproductionIncreasedsysnthesisofhydrocortisoneandadrenocorticotropichormone(ACTH)Productionofacutephaseproteins

C-reactiveproteinbindstomembranesofcertainmicroorganismstoactivatethecomplementsystem2020/12/1016CytokinesplayakeyroleinInflammationIL-1,IL-6andtumornecrosisfactora(TNF-a)ReleasedbyactivatedmacrophagesInduceadhesionmoleculesonthewallsofvascularendothelialcellstowhichneutrophils,monocytesandlymphocytesadherebeforemovingoutofthevessel(extravasation)toaffectedtissueInducecoagulationandvascularpermeabilityIncreasedchemotaxisforleukocytesandincreasedphagoctosis(IL-8andinterferon-g)Alltheseeffectsresultinaccumulationoffluid(edema)andleukocyticcellsintheinjuredarea.Amplifyresponsebytransportingotherbiologicallyactivecompoundstositeandaccumulatedcellsattractingandactivatingmorecells2020/12/1017OtherBiologicallyActivatedSubstancesDegradativeenzymesToxicfreeradicalsAcidsGrowthinhibitorsAcutephaseproteinsInterferonsHarmfultomicroorganinsInfluencedbyage,raceandhormonalandmetabolicstatus2020/12/1018Mostcellsinvolvedininflammationarephagocyticcells:Atfirst,mainlypolymorphonuclearleukocytesAccum