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1、MucosalImmunization黏膜免疫ImmuneResponse.Innateimmunity:macrophages,NKcells,mucous,lysozyme,cytokines,etc.Providesfirstlineofdefensetopreventcolonizationandinfection.DetermineswhichantigenswillberecognizedbyB-andT-cellsandthenatureoftheresponse.ImmuneResponse.Ac
2、quiredimmunity:B-andT-lymphocytes.B-cells:produceantibodiesthatneutralizevirusesandbacterialtoxins,blockattachmentofmicrobestohostcells,oropsonizemicrobesforphagocytosisT-cells:help(CD4+)orcytotoxic(CD8+)functions(eliminationofintracellularmicrobesandviruses)
3、Pathogen-associatedmolecularpatterns(PAMPs).Conservedmolecularstructuresfoundonbacterialandviralpathogens.Examples:Gram+and–bacteria:LPS,teichoicacid,peptidoglycans,CpGmotifsRNAvirus:dsRNAYeasts:mannansPathogen-associatedmolecularpatterns(PAMPs).Notpresentonm
4、ammaliancellsbutinteractwithnon-clonalpatternrecognitionreceptors(PPRs)onmacrophages,dendriticcells,epithelialcells.Examples:CD14,collectins,toll-likereceptors(TLRs),mannosebindingprotein(MBP),serumamyloidP,C’receptors,CD11b/CD18,DEC205PAMPsandPPRs:Mechanismo
5、factivation.Example:bacterialCpGbindstoTLR9BindingofmicrobialmoleculestoTLRstransducessignalsthroughacommonadaptor(MYD88)andNFkBresultinginthegenerationofcytokines(IL-1,IL-12,TNF-a)andactivationmolecules(B7)onlymphocytes.Enhancesantigenpresentation,T-cellacti
6、vation,increasesadaptiveimmuneresponse.MucosalEpithelialCells.Interfacebetweenpathogenandimmunesystem:Innate(MHCClassI)andinducible(MHCClassII)antigenpresentationfunctionInducedbypathogenstosynthesizeandsecrete:AntimicrobialpeptidesandproteinsImmunoregulatory
7、cytokinesColony-stimulatingfactorsChemokines(recruitmentofimmunecells)HelperT-CellSubsets.TH1:IFN-g,TNF-bCellularimmunityvs.intracellularbacteria,smallparasitesInductionofneutralizingantibodiesoftheIgG2asubclass(inmice)TH2:IL-4,IL-5,IL-10,andIL-13Inducedbyhel
8、minthparasites,allergens,immunizationwithsolubleoralum-adsorbedantigensImmunitytoextracellularparasites,bacteriaHelperfunctioninproductionofIgA,IgE,andneutralizingIgGtobacterialtoxinsRegu