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1、TumorImmunobiochemistry1.ThesurveillianceSystemandcancer2.Naturalkiller(NK)cell3.Antibody4.MHCproteinsFordecades,theimmunesurveillancesystemhasbeencreditedwithprotectingthebodyagainstcancer.Presumably,cancerdevelopsoccasionallyduringalifetimeandthesurveillancesystemisa
2、bletoeradicateitfromthebody.1.ThesurveillanceSystemandcancerItisonlywhenacancerescapesthissystemorthesystembecomesweakenedthatcancercanbecomeestablished.Insomecases,thecancercellsareable,biochemically,toescapetheimmunesurveillancesystem.机体的抗肿瘤免疫效应机制包括细胞免疫和体液免疫细胞免疫的效应细胞
3、包括T细胞,NK细胞,巨噬细胞,目前认为中性粒细胞、嗜酸性粒细胞也参与抗肿瘤作用。激活补体系统溶解肿瘤细胞,抗体依赖的细胞介导的细胞毒作用,抗体的调理作用,抗体封闭肿瘤细胞上的某些受体,抗体使肿瘤细胞的粘附特性改变或丧失ThesurveillianceSystem2.Naturalkiller(NK)cellNKcellsaresubsetofTcellsthatcankilltumorcells(orvirus-infectedcells)butdonotharmnormalcellsNKcellsalsoareheteroge
4、neous;theycontainsubsetsofcells,atleastoneofwhich(A-NKcells)iscapableofkillingtumorcellsandcellsinfectedwithvirusesTheA-NKcellhasavarietyofreceptorsonitscellularsurfaceTu15-12Tu15-12Tu15-12图15-1OneormoreofreceptorswillrecognizeanantigenonthesurfaceofthetumorcellThisan
5、tigen,notexpressedonmostnormalcells,isanMHCclassIchain-relatedantigen,theantigenbindstoNKG2D,ac-lectin-likereceptoronthesurfaceofhumanNKcellsThecomplexwiththeantigencaninitiatethekillingprogramthroughpI3kNKG2Disnon-covalentlyassociatedtotheDAP10transmembranesignalin
6、gadaptor.Killercellshaveatleasttwomechanismstodestroytumorcells*perforin-granzyme-mediatednecrosis*FasL/FaspathwayinduceapoptosisTu15-12Tu15-3Tu15-3Tu15-3Tu15-3Tu15-4WhycanNKcellkilltumorcellsbutdonotharmnormalcellsTwoofreceptorsonthesurfaceoftheNKcellarekillercellinhi
7、bitoryreceptorKIR,(KIR2DL2),anexampleofanimmunoglobulin-likereceptor,andLy-49A,normalcellsexpressanMHCclassIchain-relatedantigeneitheratverylowlevelsornotatall,andA-NKcellsthataresurveyingthemicroenvironmentdonotattackthemontheotherhand,NKcellshavereceptorsthatrecogniz
8、enormalantigensonnormalcells;thiscomplexinhibitsthekillingprogramTu15-9Tu15-103.AntibodyAntibodies(Abs)arespecificmol