特异免疫应答_精品文档.ppt
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特异免疫应答_精品文档.ppt
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SpecificImmuneResponse,Reading:
Rangetal,Chapter12,LocalHormones,Inflammation&AllergyThekeycellsinvolvedinthespecificimmunologicalresponseareLYMPHOCYTES,fallinginto3maingroups:
1.BCellsresponsibleforantibody(Ab)production2.TCellsimportantintheInductionPhaseandresponsibleforcell-mediatedresponse3.NKCellsNaturalKillerCells,specialisednon-T,non-Bcellsthatareactivatedinthe“innateresponse”Inthespecificimmuneresponsethereare2mainphases:
1.InductionPhase2.EffectorphaseThisisfurthersubdividedinto:
2a.HumoralComponent(Antibody-mediated)2b.Cell-mediatedComponent,SpecificImmuneResponse,SpecificImmuneResponse,InductionPhaseThisinvolvestheactivationofTcellsandBcellswhenaforeignantigen(Ag)ispresentedtoanaveHelperTCellbyanAntigenPresentingCell(APC).Remember:
Antigenanyforeigncompoundthatinitiatesanimmuneresponseusuallyaproteinorpolysaccharideoftenfoundonthesurfaceofmicroorganisms,transplantedtissues/organs,foodsetc.AntibodyspecificallyproducedtoneutraliseONEtypeofAntigen.ProducedbyBcellsblueprintiskeptbyMemoryTcells,SpecificImmuneResponse,InductionPhaseAntigensreachthelocallymphnodesviathelymphatics.TheantigenispresentedtolymphocytesbyAntigenPresentingCells.TheAPCsingestandprocesstheAgandpresentittoanuncommittedornaveCD4-positiveHelperTcellinconjunctionwiththeMHC.ThesenaveHelperTCellsbegintoproduceInterleukin-2-receptorsaswellasgeneratingInterleukin-2.Interleukin-2isacytokinethathasanautocrinefunction,thatis,itcausestheproliferationofactivatedHelperTCellswhicharenowcalledTh0cells.Th0cellsthenproduceeitherTh1orTh2cellsTh2cellproductionisstimulatedbyIL-4(Interleukin-4)fromTh0cells.Th1cellproductionisstimulatedbyIK-12(Interleukin-12)secretedfromtheAPCsafterbindingtoHelperTcells.,SpecificImmuneResponse,Figure20-10Vanderetal,8thEd.,SpecificImmuneResponse,ThesenaveHelperTCellsbegintoproduceInterleukin-2-receptorsaswellasgeneratingInterleukin-2.,Interleukin-2isacytokinethathasanautocrinefunction,thatis,itcausestheproliferationofactivatedHelperTCellswhicharenowcalledTh0cells.,Th0cellsthenproduceeitherTh1orTh2cells,Th1cellproductionisstimulatedbyIK-12(Interleukin-12)secretedfromtheAPCsafterbindingtoHelperTcells.,Th2cellproductionisstimulatedbyIL-4(Interleukin-4)fromTh0cells.,SpecificImmuneResponse,Th2cellsundertheinfluenceofIL-4willpromotetheproliferationofBCellswhichareresponsibleforourAntibodymediatedimmuneresponses.SomeBCellsbecome:
PlasmaCellsandreleaseAbintoblood.MemoryBCellsthatretaintheblueprintoftheAgforfutureAbproductionshouldthesameAgenterthebodylater.,InductionPhase,SpecificImmuneResponse,InductionPhase,Th1cellsproduceseveralcytokinesbutmfactivatingcytokinesandInterferongaremostimportantinitially.InterferongisresponsibleforstimulatingCD8TCellstobecomeCytotoxicTCellsThisisthebeginningofthecell-mediatedpathwayoftheimmuneresponse.,SpecificImmuneResponse,Figure12.3Rangetal.,SpecificImmuneResponse,SpecificImmuneResponse,InductionPhaseSummaryThe2subsetsofTCellsareimportantbecausetheyareresponsibleforprovidingthebalanceinresponsebytheimmunesystem.AlsoanydysfunctionatthislevelwillleadtodeficienciesinbothAb-mediatedand/orcell-mediatedimmunity.Th1CellsandCell-MediatedImmunityTh1Cellsproducethecytokines(IL-2,TNF-bandIFNg)that:
activatemacrophagesstimulateCD8+lymphocytestoreleaseIL-2yieldingcytotoxicTcellsinhibitTh2cellsbyINFgaction.Th2CellsandAb-MediatedImmunityProducecytokines(IL-4,TGF-b,IL-10)that:
StimulateBCellproliferation(CD4+Cells)StimulatedifferentiationofeosinophilsInhibitTh1Cellfunction.,SpecificImmuneResponse,EffectorPhaseAntibody-Mediated(Humoral)ResponseAbsareimmunoglobulins(Igs)thathave2functions:
1.RecognizeandinteractspecificallywithforeignAgs.2.Activateoneofmorehostdefencemechanisms.StructureofAntibodiesY-shapedproteinscontaining:
FabportionthathastherecognitionsiteforAgFcportionthatactivateshostdefences.,SpecificImmuneResponse,EffectorPhaseAmongBcellsthereareclonesthatexpressindividualAbstorecognizespecificAgs.Remember5classesofIgs:
IgA,IgD,IgE,IgGandIgMAbsimprovethehostsabilitytorecoverfromaninvadingAgassociatedwithavirusorabacterialtoxin.Absinteractwithelementsoftheinnateimmunesystemasfollows:
ActivateComplementStimulateIngestionofBacteriaAssistCytotoxicCellFunctionStimulateAllergicReactions,SpecificImmuneResponse,AbandComplementAbbindstoAgforminganAg-AbComplex.ThisexposestheFcportionoftheAbwhichisabindingsiteforComplement.Complement-FcComplexresultsinactivationofthecomplementsequence,particularlytheClassicalPathway.
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