Chapter 3 Outline Introduction conception of Ab and

Chapter 3

Outline ØIntroduction (conception of Ab and Ig) ØStructure of Immunoglobulin ØFunction of Immunoglobulin ØCharacteristics and Functions of 5 Ig Classes ØMonoclonal Antibody

Ⅰ. Introduction 1. Antibody (Ab) neutralize exotoxin bacteria Ag antitoxin animal agglutinate specific (in serum) substanceagglutinin Ab 含有抗体的血清 称为免疫血清 Discovery of antibody

Conception of Ab Ag → B cell ↓ plasma cell ↓ globulin (antibody) • can combine with corresponding Ag • immune functions 抗体是B细胞受抗原刺激后, 增 殖分化为浆细胞所产生的一种能与 相应抗原结合、具有免疫功能的球 蛋白 Physicochemical properties of Ab 球蛋白 • gamma-globulin • heterogenicity (异质性) 正常人血清电泳分离图

2. Immunoglobulin (Ig) A. Conception 具有抗体活性或化学结构与抗体 相似的球蛋白统称为免疫球蛋白(Ig) B. Expression of Ig Secreted Ig (SIg) Membrane Ig (m. Ig )

Ⅱ. Structure of Ig 1. Basic structure of Ig * tetrapeptide chain structure * monomer of Ig (appear Y shaped) ---basic unit of Ig molecule

H chain ( , , ) V region (Ag-biding site) L chain κ/λ (2: 1) C region H 2 L 2 2 region hinge region Monomer of Ig

Ag-biding site ---made up of VH and VL (HVR/CDR) HVR 1/CDR 1 FR 2 HVR 2/CDR 2 HVR 3/CDR 3 FR 4 HVR (hypervariable region) CDR(complementarity determining region) FR (framework region)

2. Domain of Ig Ig. G VH/VL --- Ag-binding site (HVR/CDR) CH 1/CL ---genetic marker of allotype CH 2 --- complement C 1 q binding site (CH 3 of Ig. M) CH 3, 4 --- binding to Fc. R on surface of cells(CH 2, 3 of Ig. E binding to Fc R) 19

3. Hydrolytic fragment of Ig (pepsin) (papain) 1 F(ab’)2 +p. Fc’ 2 Fab + 1 Fc

4. Joining chain ＆ secretory piece A. Joining chain n(H 2 L 2) J chain (H 2 L 2)n J n(monomer) polymer (H 2 L 2)2 J dimer (H 2 L 2)5 J pentamer B. Secretory piece (SP) or secretory component (SC) ---保护SIg. A并介导Ig. A分泌到粘膜表面 C. Secretory Ig. A: (H 2 L 2)2 -SC-J

Ⅲ. Functions of Ig 1. V region (recognize and combine with Ag specifically) neutralize exotoxin and virus inhibit adhesion agglutinate bacteria 阻止病原体入侵 溶解细胞/细菌 调理作用 激活补体 中和作用 通过胎盘 2. C region activate complement binding to Fc. R on surface of cells transfer across placenta (Ig. G) 与Ag特异性结合 结合Fc受体 ADCC 调理作用 介导Ⅰ型超敏反应 被动免疫

Immunoglobulin Superfamily 1. Conception and structure of Ig. SF A. Conception 一类具有Ig. V区和/或C区相似的折叠结构, 氨基酸 序列有一定同源性的膜蛋白称为免疫球蛋白超家族 B. Structure 2. Functions of Ig. SF A. Recognize Ag (TCR, BCR) B. Interaction between cells (CD 4/CD 8 - -MHC; CD 28 -B 7; LFA-ICAM) C. Transmit signal (CD 3; Ig /Ig )

p 106 *Diversity and structure of BCR gene 1. Structure of BCR gene V region (14) V region--H: V, D and J L: V and J C region V D J 连接成一个连 续的DNA, 编码V区 C region--H: C , C … L: C , C (2) (22) （四个J-C 对） p 106

2. Diversity and Rearrangement of BCR gene • Rearrangement of H chain D 2 joins with JH 2 VH 1 joins with D 2 JH 2 • Diversity *为数众多的编码Ig 基因在重排时的多样 性组合和连接 *体细胞的突变 transcription VH joins with C or C translation H chain