特异性B淋巴细胞应答免疫学课件.ppt

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1、1第十七章特异性B淋巴细胞应答中南大学基础医学院免疫学系田伟博士，教授ImmunityandtheImmuneResponseSystemHumoralorB-CellMediatedImmuneResponseProducessecretedantibodies(proteins)Bindtoantigensandidentifytheantigencomplexfordestruction.EachBlymphocytemakesauniqueantibodymolecule(immunoglobulinorIg).Overa

2、milliondifferentBlymphocytesareproducedineachindividual.ActivationofBLymphocytesandProductionofAntibodiesAntibodiesareproducedbyBlymphocytesandtheirprogeny.NaiveBlymphocytesrecognizeantigensbutdonotsecreteantibodies.Plasmacellssecreteantibody.ImmunologicallyNaiveNoprevi

3、ousexperienceNomemoryBCellReceptorComplex第一节B细胞对TD抗原的免疫应答1113活化辅助受体组成：CD19/CD21/CD81CD19胞浆区有9个Tyrosine残基，募集含SH2结构域的信号分子。加强了由BCR复合物传导的信号，明显降低抗原激活B细胞的阈值，从而大大提高了B细胞对抗原刺激的敏感性。14信号1：BCR直接识别抗原表位,CD19/CD21/CD81为辅助受体.信号2：T细胞B细胞CD40L……CD40ICAM-1，2，3……LFA-1细胞因子：IL-4、5、6B细胞活化所需要的信

4、号15Two-SignalModelofHumoralImmuneResponseActivationandMigrationActivatedhelperT-cells(effectorcells)interactwithAg-stimulatedB-cellsatedgeoffolliclesinlymphoidtissueB-CellActivation20B细胞T细胞抗原识别受体BCRTCR转导信号分子Igα/IgβCD3ITAM（p）化后第一个被募集的PTKSykZAP-70GEFs激活的小G蛋白Ras和RacRas辅助受体

5、CD19/21/81CD4/CD8BCR复合物与T细胞复合物介导的细胞信号转导的差别GerminalCenters(GC)Function:togenerateBcellsthatproduceantibodieswithincreasedaffinityfortheinducingantigen=>affinitymaturationGerminalCenterReaction:ActivatedBcellsgiverisetoCentroblasts-localizeinfollicle,undergorapidcelldivis

6、ionandturnonmachinerythatcausessomaticmutationinV-regionsCentroblastsgiverisetoCentrocytesSeveralimportantmodificationsoccurintheGC;somatichypermutation,affinitymaturationandisotypeswitching.Ki67FDCCD4TSomatichypermutationAffinityMaturationAffinityofAbproducedtoproteinA

7、gincreaseswithprolongedorrepeatedexposurestothatAgAbbindingtomicrobeorAgincreasesifinfectionispersistentorrecurrentduetopointmutationsintheVregion–AgbindinghypervariableregionhappensonlyinT-dependentproteinAgmutationrate1:1000nucleotides–somatichypermutationAffinityMatu

8、rationIsotypeSwitchingHeavyclasschainisswitchedtoadifferentisotypetobroadenfunctionalcapabilities.HelperT-cell