《医学免疫学教学》03 antibody

1、Outline of the lectureEmil von Behring (1845-1917)antibody-In 1890 by von Behring and Kitasato described an activity in serum of toxin-immunized animals that neutralized toxin. Transfer of immune serum could protect nave animals from diphtheria or tetanus.HistoryDay 02468Resting B cellAntibodyformin

2、g cell,AFC(plasma cell)YYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYOutline of the lecturenBasic structurenHeavy chain and Light chain（重链和轻链）（重链和轻链）nVariable region and Constant region（可变区和恒定区）（可变区和恒定区）nOther structuresnHinge region（铰链）（铰链）nJoining chain （J链）链）n Secretory component (SC，分泌片，分泌片)nDomains （功能区）（功能

3、区）nFragmentation of Ig by proteolytic cleavage人：人： 2：1，小鼠：，小鼠：20：1 1) Heavy chain (H) & Light chain (L)2) Variable region (V region) and constant region (C region) V regions (VL+VH) are the site where antigens bind specifically to antibodies.Fab (antigen binding fragment) are the N-terminal half

4、 of the H-chain and all of the L-chain. Fc (crystallized fragment) are the C-terminal half of the H-chain fragment that crystallized).FabFcHypervariable regions (HV, CDR) and framework regions (FR)Domains of Ig 3) Other structures(1) Hinge region Flexibility of immunoglobulinsJoining chain aid to co

5、mbine monomers into polymers. Five molecules of IgM usually polymerize into a larger pentamer. Secretory IgA is a dimmer.Secretory component (SC) can prevent the secretory IgA dimmers from degradation of other proteases. Secretory IgA always distribute on lumenal surface.(2) Joining chain and secret

6、ory component (SC)Secretory IgA is a dimmerIgM polymerize into a pentamerBoth H- and L- chains have intrachain disulfide bridges every 90 amino acid residues, which create polypeptide loops, domains, of 110 amino acids.免疫球蛋白的功能区免疫球蛋白的功能区-H chain Variable region is one domain, referred to as VH; cons

7、tant region has three or four domains, referred to as CH1, CH2, CH3, CH4.(IgG, IgA, IgD has three domains-CH1, CH2, CH3 in C region; while IgM, IgE has four domains-CH1, CH2, CH3, CH4 in C region). -L-chain Variable region is one domain, referred to as VL; constant region also has only one domain, r

8、eferred to as CL. 3. Immunoglobulin fragmentsOutline of the lectureOutline of the lecturepeptidepeptideepitopebinding of HV and epitope C C区的功能区的功能 激活补体激活补体 IgMIgM和和IgGIgG与抗原形成免疫复合物后能与抗原形成免疫复合物后能激活补体经典途径激活补体经典途径； 凝聚的凝聚的IgG4IgG4和和IgAIgA能激活补体旁路激活途径能激活补体旁路激活途径 与免疫细胞表面与免疫细胞表面FcRFcR结合结合 1 1）调理作用（调理作用（ops

9、onization)opsonization) IgFc IgFc段与吞噬细胞表面段与吞噬细胞表面FcRFcR结合结合，促进吞噬细胞的吞噬作用；，促进吞噬细胞的吞噬作用； 2 2）抗体依赖细胞介导的细胞毒作用（抗体依赖细胞介导的细胞毒作用（Ab-dependent cell-mediated cytotoxicity,ADCC) ) IgFc IgFc段与段与NKNK细胞等表面细胞等表面FcRFcR结合结合，促进，促进NKNK细胞的细胞毒作用；细胞的细胞毒作用； 3) 3) 介导介导I I型超敏反应型超敏反应 IgE FcIgE Fc段与肥大细胞等表面段与肥大细胞等表面FcRFcR结合结合，介

10、导，介导型超敏反应型超敏反应。 穿过胎盘和粘膜穿过胎盘和粘膜 IgGIgG通过胎盘，提供被动免疫保护；通过胎盘，提供被动免疫保护； sIgAsIgA穿过粘膜，参与黏膜局部的抗感染免疫。穿过粘膜，参与黏膜局部的抗感染免疫。IgE can induce the class I hypersensitivity.肥大细胞表面表达高亲和力肥大细胞表面表达高亲和力的的IgE Fc受体（受体（FcRI）。）。IgE与变应原结合，导致与变应原结合，导致FcRI发生交联就能激活肥大发生交联就能激活肥大细胞，导致其脱颗粒，释放生细胞，导致其脱颗粒，释放生物活性介质，导致物活性介质，导致型超敏反型超敏反应的发生。

11、应的发生。-Mast cells and basophils have receptors for Fc portion of IgE. Binding of antigens to IgE already bound to Fc receptors for IgE on mast cells results in degranulation and inducing the type I hypersensitivity.IgE can induce the class I hypersensitivity.粘膜免疫粘膜免疫Outline of the lecture immunoglobu

12、lin classesThese are monomer forms as they appear when expressed as a B cell antigen receptor. When secreted, the structures can be quite different. IgM is a pentamer in serum, and IgA can be a dimer.多能免疫球蛋白多能免疫球蛋白初次应答与再次应答初次应答与再次应答 由脊髓灰质炎病毒引起，由脊髓灰质炎病毒引起，从消化道感染，粘附于肠从消化道感染，粘附于肠道粘膜细胞并进入血液，道粘膜细胞并进入血液，使

13、脊髓灰质前角的运动神使脊髓灰质前角的运动神经元受损，导致肌肉麻痹，经元受损，导致肌肉麻痹，特别是下肢瘫痪。特别是下肢瘫痪。脊髓灰质炎减毒活疫苗脊髓灰质炎减毒活疫苗（糖丸）（糖丸）sIgA脊髓灰质炎（小儿麻痹）：脊髓灰质炎（小儿麻痹）：mIgMmIgD成熟成熟B细胞细胞活化活化B细胞细胞未成熟未成熟B细胞细胞CH4CH4Outline of the lecture第一代抗体第一代抗体polyclonal antibody，PcAb (多克隆抗体多克隆抗体)第二代抗体第二代抗体Monoclonal antibody，McAb (单克隆抗体单克隆抗体)第三代抗体第三代抗体Genetically en

14、gineering Ab, GeAbRecombinant antibody ，ReAb(基因工程抗体基因工程抗体/重组抗体重组抗体)蛋白质抗原分子蛋白质抗原分子1 1、2 2、3 3、4 4、5 5表示表示B B细胞决定基细胞决定基针对多种抗原决定基的针对多种抗原决定基的多种抗体的混合物多种抗体的混合物带有多个带有多个B细细胞表位胞表位抗原抗原针对不同表位针对不同表位的的B细胞细胞克隆增殖克隆增殖多种抗体的混合物多种抗体的混合物（多克隆抗体）（多克隆抗体）刺激小鼠刺激小鼠H H：次黄嘌呤：次黄嘌呤A A：氨基蝶呤：氨基蝶呤T T：胸腺嘧啶：胸腺嘧啶聚乙二醇聚乙二醇特异性特异性敏感性敏感性均一性均一性McAbPcAb低低差差无无高高强强有有1、用于免疫学检测，辅助临、用于免疫学检测，辅助临床诊断床诊断2、McAb用于亲和层析，分用于亲和层析，分离微量可溶性抗原离微量可溶性抗原3、标记的、标记的McAb用于基础研用于基础研究，了解细胞分化等究，了解细胞分化等4、制备生物导弹用于肿瘤、制备生物导弹用于肿瘤、移植等的临床治疗移植等的临床治疗（一）人（一）人-鼠嵌合抗体鼠嵌合抗体（二）人源化抗体（二）人源化抗体只有互补决定区（只有互补决定区（CDRCDR）是鼠源的）是鼠源的其余部位都是人源的其余部位都是人源的V V区是鼠源的区是鼠源的C C区是人