Gene-X-ppt(Gene10-基因十)--Chapter18

Chapter18SomaticRecombinationandHypermutationintheImmuneSystem18.1TheImmuneSystem:InnateandAdaptiveImmunity•antigen–Amoleculethatcanbindspecificallytoanantigenreceptor,suchasanantibody.•Bcell–Alymphocytethatproducesantibodies.Developmentoccursprimarilyinbonemarrow.–Bcellsemergingfromthemarrowundergofurtherdifferentiationinthebloodstreamandperipherallymphoidorgans.18.1TheImmuneSystem:InnateandAdaptiveImmunity•Tcells–LymphocytesoftheT(thymic)lineage.Tcellsdifferentiateinthethymusfromstemcellsofbonemarroworigin.–Theyaregroupedinseveralfunctionaltypes(subsets)accordingtotheirphenotype,mainlyexpressionofsurfaceproteinsCD4andCD8.–DifferentTcellsubsetsareinvolvedindifferentcell-mediatedimmuneresponses.18.1TheImmuneSystem:InnateandAdaptiveImmunity•adaptive(acquired)immunity–Theresponsemediatedbylymphocytesthatareactivatedbytheirspecificinteractionwithantigen.–Theresponsedevelopsoverseveraldaysaslymphocyteswithantigen-specificreceptorsarestimulatedtoproliferateandbecomeeffectorcells.–Itisresponsibleforimmunologicalmemory.18.1TheImmuneSystem:InnateandAdaptiveImmunity•Bcellreceptor(BCR)–ThereceptorforantigenexpressedonthesurfaceofBlymphocytes.–TheBCRhasthesamestructureandspecificityoftheantibodythatwillbeproducedbythesameBcellafteritsactivationbyantigen.18.1TheImmuneSystem:InnateandAdaptiveImmunity•Tcellreceptor(TCR)–TheantigenreceptoronTlymphocytes.–ItisclonallyexpressedandbindstoacomplexofMHCclassIorclassIIproteinandantigen-derivedpeptide.•humoralresponse–Animmuneresponsethatismediatedprimarilybyantibodies.Itisdefinedasimmunitythatcanbetransferredfromoneorganismtoanotherbyserumantibody.18.1TheImmuneSystem:InnateandAdaptiveImmunity•innateimmunity–Aresponsetriggeredbyreceptorswhosespecificityispredefinedforcertaincommonmotifsfoundinbacteriaandotherinfectiveagents.–ThereceptorthattriggersthepathwayistypicallyamemberoftheToll-likereceptor(TLR)family,andthepathwayresemblesthepathwaytriggeredbyTollreceptorsduringembryonicdevelopment.–Thepathwayculminatesinactivationoftranscriptionfactorsthatcausegenestobeexpressedwhoseproductsinactivatetheinfectiveagent,typicallybypermeabilizingitsmembrane.18.2TheInnateResponseUtilizesConservedRecognitionMoleculesandSignalingPathways•Innateimmunityistriggeredbypatternrecognitionreceptors(PRRs)thatrecognizehighlyconservedmicrobe-associatedmolecularpatterns(MAMPs)foundinbacteria,viruses,andotherinfectiousagents.•PAMPs–Pathogen-associatedmolecularpatterns,nowreferredtoasMAMPs,arebroadlyconservedmicrobialcomponents,includingbacterialflagellinandlipopolysaccharides,thatarerecognizedbyPRRs,whichcriticallyinitiateinnateimmuneresponses.FIGURE01:Innateimmunity18.2TheInnateResponseUtilizesConservedRecognitionMoleculesandSignalingPathways•Toll-likereceptors(TLRs)areimportantPRRsthatdirectlyactivateinnateimmuneresponses.•TLRsignalingpathwaysarehighlyconservedfrominvertebratestovertebratesandananalogouspathwayisfoundinplants.•TLRsareexpressedindendriticcells(DCs),macrophages,andneutrophils.•TLRsareexpressedinBlymphocytesandsomeTlymphocytes.18.2TheInnateResponseUtilizesConservedRecognitionMoleculesandSignalingPathways•Toll/interleukin1/resistance(TIR)domain–ThekeysignalingdomainuniquetotheTLRsystem.–TIRislocatedinthecytosolicfaceofeachTLR,andalsoinTLRadaptors.–SimilartotheTLRs,theadaptorsareconservedacrossmanyspecies.–TheseadaptorsareMyD88,MyD88-adaptor-like(MAL,alsoknownasTIRAP),TIR-domain-containingadaptorproteininducingIFN(TRIF;alsoknownasTICAM1),TRIF-relatedadaptormolecule(TRAM;alsoknownasTICAM2),andsterilearmadillo-motif-containingprotein(SARM).18.3AdaptiveImmunity•HelperT(Th)cellsproducesignalsrequiredbyBcellstoenablethemtodifferentiateintoantibody-producingcells.•complement–Asetof~20proteinsthatfunctionthroughacascadeofproteolyticactionstolyseinfectedtargetcells,ortoattractmacrophages.•cell-mediatedresponse–TheimmuneresponsethatismediatedprimarilybyTlymphocytes,anddefinedbasedonimmunitythatcannotbetransferredfromoneorganismtoanotherbyserumantibody.FIGURE04:Antibodiesinteractwithantigens18.3AdaptiveImmunity•CytotoxicTcells(CTLs)orkillerTcellsareresponsibleforthecell-mediatedresponseinwhichfragmentsofforeignantigensaredisplayedonthesurfaceofacell.–ThesefragmentsarerecognizedbytheTCRexpressedonthesurfaceofTcells.FIGURE05:T-cellreceptorbindsantigenfragments18.3AdaptiveImmunity•InTCRrecognition,theantigenmustbepresentedinconjunctionwithamajorhistocompatibilitycomplex(MHC)molecule.•autoimmunedisease–Apathologicalconditioninwhichtheimmuneresponseisdirectedtoselfantigen.18.4ClonalSelectionAmplifiesLymphocytesThatRespondtoGivenAntigens•clonalselection–Thetheoryproposedthateachlymphocyteexpressesasingleantigenreceptorspecificityandthatonlythoselymphocytesthatbindtoagivenantigenarestimulatedtoproliferateandtofunctionineliminatingthatantigen.–Thus,theantigenselectsthelymphocytestobeactivated.–Clonalselectionwasoriginallyatheory,butitisnowanestablishedprincipleinimmunology.FIGURE06:Antigenrecognitiontriggersclonalexpansion18.4ClonalSelectionAmplifiesLymphocytesThatRespondtoGivenAntigens•EachBcellexpressesasi