肿瘤免疫生化医学医药课件.ppt

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1、TumorImmunobiochemistry1.ThesurveillianceSystemandcancer2.Naturalkiller(NK)cell3.Antibody4.MHCproteinsFordecades,theimmunesurveillancesystemhasbeencreditedwithprotectingthebodyagainstcancer.Presumably,cancerdevelopsoccasionallyduringalifetimeandthesurveillancesystemisabletoeradicateitfromth

2、ebody.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

3、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)butdonotharmnormalcellsNKcellsalsoareheterogeneous;theycontainsubsetsofcells,atleastoneofwhich(A-NKcells)iscapa

4、bleofkillingtumorcellsandcellsinfectedwithvirusesTheA-NKcellhasavarietyofreceptorsonitscellularsurfaceTu15-12Tu15-12Tu15-12图15-1OneormoreofreceptorswillrecognizeanantigenonthesurfaceofthetumorcellThisantigen,notexpressedonmostnormalcells,isanMHCclassIchain-relatedantigen,theantigenbindsto

5、NKG2D,ac-lectin-likereceptoronthesurfaceofhumanNKcellsThecomplexwiththeantigencaninitiatethekillingprogramthroughpI3kNKG2Disnon-covalentlyassociatedtotheDAP10transmembranesignalingadaptor.Killercellshaveatleasttwomechanismstodestroytumorcells*perforin-granzyme-mediatednecrosis*FasL/Faspat

6、hwayinduceapoptosisTu15-12Tu15-3Tu15-3Tu15-3Tu15-3Tu15-4WhycanNKcellkilltumorcellsbutdonotharmnormalcellsTwoofreceptorsonthesurfaceoftheNKcellarekillercellinhibitoryreceptorKIR,(KIR2DL2),anexampleofanimmunoglobulin-likereceptor,andLy-49A,normalcellsexpressanMHCclassIchain-relatedantigeneith

7、eratverylowlevelsornotatall,andA-NKcellsthataresurveyingthemicroenvironmentdonotattackthemontheotherhand,NKcellshavereceptorsthatrecognizenormalantigensonnormalcells;thiscomplexinhibitsthekillingprogramTu15-9Tu15-103.AntibodyAntibodies(Abs)arespecificmol