双语第十三章b淋巴细胞介导的体液免疫应答.ppt

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1、第十三章 B淋巴细胞介导的体液免疫应答,Section 13 humoral immune response mediated by B lymphocyte,第一节 B细胞对TD抗原的免疫应答,Chapter 1 B cell response to T cell-dependent antigen,Antigen recognition of B cells,B cell recognizes and binds an antigen in its free,unprocessed form through BCR.No MHC restriction.,一、B细胞对TD抗原的识别,BCR

2、特异性结合抗原，产生B细胞活化的第一信号；B细胞内化与其BCR结合的抗原，并进行加工处理，形成抗原肽-MHC类分子复合物，提呈给抗原特异性Th细胞识别。BCR识别的抗原无需经APC的加工和处理，也无MHC限制性。,Double signals for B cells activation,Antigen signal:recognition of antigen by the BCR Ig/Ig(CD79a/CD79b):transmit antigen stimulus signal Co-receptors:CD19/CD21/CD81accessory signal CD40 CD40L

3、,二、B细胞活化需要的信号,B细胞活化的第一信号：BCR特异性结合抗原启动第一信号，经由Ig/Ig传导入胞内，B细胞共受体(CD19/CD21/CD81)加强信号的传导；B细胞活化的第二信号（协同刺激信号）CD40/CD40L（活化的Th细胞）,Clustering of BCR,MAPK pathway,Activation of transcription factors,genes transcription and expression,Activation of associated tyrosine kinases,Signals transduction of B cell ac

4、tivation,Cytoplasmic domain of Ig/Igare phosphorylated,Syk is recruited and activated,PLC-pathway,B细胞活化的信号转导途径,BCR交联,PLC-活化途径,MAP激酶活化途径,转录因子活化,相关基因转录,SyK被募集并活化,Ig/Ig胞质区ITAM磷酸化,活化酪氨酸激酶（Blk、Fyn或Lyn）,Interaction between TH and B cells,TH cells provide accessory signal（CD40/CD40L）and cytokines(Th1 IL-2、

5、IFN-、Th2 IL-4、5、6)for B cells activation and differentiation.B cells provide antigen signal（peptide-MHC complex）and costimulatory signal（B7/CD28）for TH cells activation.,T、B细胞相互作用,Th细胞辅助B细胞免疫应答Th细胞提供B细胞活化的第二信号（CD40/CD40L）；Th细胞分泌多种细胞因子协助B细胞分化(Th1 IL-2、IFN-、Th2 IL-4、5、6)B细胞作为APC活化T细胞B细胞提供T细胞活化的第一信号（抗原

6、肽-MHC类分子复合物）活化的B细胞提供T细胞活化的第二信号（B7/CD28）,Proliferation and terminal differentiation of B cells,Activated CD4+Th secrete cytokines which act on B cells,Th1:IL-2 IFN-Th2:IL-4 IL-5 IL-6,三、B细胞的增殖和终末分化,细胞因子信号,Th1:IL-2 IFN-Th2:IL-4 IL-5 IL-6,活化的CD4+Th细胞分泌细胞因子，作用于B细胞。,Th细胞对B细胞的辅助作用发生于外周淋巴器官的T细胞区和生发中心。,专职APC

7、（DC）捕捉、加工抗原,迁移至局部淋巴结的T细胞区,APC捕捉,TCR结合抗原肽-MHC分子,T细胞被激活(Th),表达该抗原特异性BCR的B细胞,B细胞被激活进入淋巴滤泡,表达该抗原特异性TCR的T细胞,增殖形成生发中心,Development and differentiation of B cells in germinal centers,The events associated with the development and differentiation involves somatic hypermutation,affinity maturation,Ig heavy-ch

8、ain class switch and memory B cell formation.,四、B细胞在生发中心的分化成熟,生发中心中绝大多数B细胞发生凋亡，部分B细胞在抗原刺激和T细胞辅助下继续分化发育，在生发中心中完成体细胞高频突变和Ig亲和力成熟、Ig类别转换，最终形成浆细胞和记忆性B细胞。,Somatic hypermutation,Fully assembled V/J and V/D/J exons in B cells undergo point mutation at an unusually high rate during the course of an immune r

9、esponse,this phenomenon is termed somatic hypermutation.Individual cells that undergo high affinity mutants and express higher affinity Ab are selected.Form the BCR diversity.,Affinity maturation,The antibodies produced later in an immune response tend to have higher affinity for the target antigen

10、than those produced earlier,this phenomenon is termed affinity maturation.Especially the antibody produced in secondary response tends to be higher affinity than that in primary response.Somatic hypermutation and antigen selection are thought to account for this phenomenon.,（一）体细胞高频突变和Ig亲和力成熟,生发中心母细

11、胞的轻链和重链V基因可发生高频率的点突变，称为体细胞高频突变；在每次细胞分裂中，IgV区基因中大约每1000个bp中就有一对发生突变；体细胞高频突变在抗原诱导下发生；再次免疫应答时抗原会优先结合高亲和力的BCR，产生高亲和力的抗体，称为抗体亲和力成熟；导致BCR多样性及体液免疫应答中抗体的多样性。,Ig heavy-chain class switching,Each mature B cell,after activation,initially expresses IgM antibodies and then undergoes switching to a different clas

12、s of antibody without changing its specificity for antigen,this phenomenon is called class switching,or isotype switching.Results from a specialized type of DNA rearrangement.depends on signaling by a TH cell.(CD40L-CD40)Influenced by cytokines produced by TH cells.,（二）Ig的类别转换,在免疫应答中首先分泌IgM，随后可表达IgG

13、、IgA或IgE，而其IgV区不发生改变，这种可变区相同而Ig类别发生变化的过程称为Ig的类别转换或同种型转换；类别转换的遗传学基础是同一V区基因与不同重链C基因的重排；Ig的类别转换在抗原诱导下发生，接受Th细胞分泌的多种细胞因子的调节。,Formation of plasma cells,Synthesize and secrete specific AbMost transfer to bone marrow and generate Ab continuouslyDont express BCR and MHC molecule,cant react to Ag and lose th

14、e ability to react with Th,（三）浆细胞的形成,又称抗体形成细胞，能合成和分泌特异性抗体；大部分迁入骨髓，在较长时间内持续产生抗体；表面不再表达BCR和MHC类分子，不能再与抗原起反应，也失去了与Th相互作用的能力；,Memory B lymphocyte,Reside in lymphoid follicles or circulate in the blood,survive for years.Have a higher affinity receptor and more readily activated to proliferate and secrete

15、 antibody by antigen stimulation in secondary response.,（四）记忆性B细胞的产生,生发中心中存活下来的B细胞，或分化发育成浆细胞，或成为记忆性细胞离开生发中心进入血液参与再循环；记忆性B细胞不产生Ig，但再次与同一抗原相遇时可迅速活化，产生大量抗原特异的Ig。,Antibody:neutralization,opsonization,complement activation and ADCC.Memory B cells,Effector,五、B细胞的效应 抗体的效应记忆性B细胞的效应,第二节 B细胞对TI抗原的免疫应答,Chapter

16、 2 B cell response to T cell-independent antigen,TI antigen,TI-1 antigenTI-2 antigen,At high concentrations TI-1 antigen acts with B cells as a mitogen.At low concentrations TI-1 antigen elicits an antigen-specific antibody response.,B cell response to TI-1 antigens,TI-1抗原,又被称为B细胞丝裂原，如LPS，成熟或不成熟的B细胞

17、均可被激活。高浓度时经丝裂原受体与B细胞结合诱导多克隆B细胞增殖和分化；低浓度时激活抗原特异性B细胞。激活初始B细胞无需Th细胞辅助，诱导产生低亲和力的IgM，单独不足以诱导Ig类别转换、抗体亲和力成熟及记忆性B细胞形成。,TI-2 antigens are generally highly repetitive polymeric antigens.TI-2 antigens activate B cells through cross-linking of BCR molecules.,B cell response to TI-2 antigens,TI-2抗原诱导B细胞的激活,多为细菌

18、胞壁与荚膜多糖，具有高度重复的结构，仅能激活成熟的B细胞，应答的主要是B-1细胞。通过其高度重复的抗原表位使B细胞的mIg广泛交联而被激活，但过度交联会使成熟B细胞出现耐受。,TI-2抗原,Dont require the presence of TH cells.Generate primarily IgM antibodies of low affinity.No somatic hypermutation,no affinity maturation,no Ig heavy-chain class switch and no memory B cells formation.,Chara

19、cteristics of B cell response to TI antigen,无Ig亲和力成熟无Ig类别转换，只能产生IgM无需Th细胞和巨噬细胞的参与无记忆性B细胞形成,不能引起免疫记忆,B细胞对TI-Ag的应答特点,第三节 体液免疫应答抗体产生的 一般规律,Chapter 3 Rules of antibody production,（一）初次应答,潜伏期(lag phase)：抗原刺激后至血清中能测到特异抗体前的阶段；对数期(log phase)：抗体量呈指数增长；平台期(plateau phase)：血清中抗体浓度基本维持在一个相当稳定的较高水平；下降期(decline ph

20、ase)：血清中抗体浓度慢慢下降。,Primary response,Most of the antigen is processed by dentritic cells.Develop in 4-5 days after antigen introduction,5-10 days required to reach peak serum antibody concentration.Achieve low antibody concentration.Duration is short.The antibodies initially produced are predominantly

21、 IgM with low antigen affinities.,Secondary response,Meromy B cells serve as the principal APCs.Activated at very low concentrations of antigen.Shorter lag peroid.Achieve high affinity and high concentration of antibody.Duration is long.IgG tends to predominate.,（二）再次应答,潜伏期短；诱发再次应答所需抗原剂量小；抗体浓度增加快，快速到达平台期，平台高；抗体维持时间长；再次应答主要产生高亲和力的抗体IgG，而初次应答中主要产生低亲和力的IgM。,