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Immunoglobulin

Chapter 3. Immunoglobulin. 免疫球蛋白. (conception of Ab and Ig). Outline. Introduction Structure of Immunoglobulin Function of Immunoglobulin Characteristics and Functions of 5 Ig Classes Monoclonal Antibody. Ⅰ. Introduction. 1. Antibody (Ab). neutralize. antitoxin.

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Immunoglobulin

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  1. Chapter 3 Immunoglobulin 免疫球蛋白

  2. (conception of Ab and Ig) Outline Introduction Structure of Immunoglobulin Function of Immunoglobulin Characteristics and Functions of 5 Ig Classes Monoclonal Antibody

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

  4. Conception of Ab Ag → B cell ↓ plasma cell ↓ globulin •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 (antibody) Physicochemical properties of Ab 球蛋白 •gamma-globulin •heterogenicity (异质性) 正常人血清电泳分离图

  5. 2. Immunoglobulin (Ig) A. Conception B. Expression of Ig 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) Secreted Ig (SIg)Membrane Ig (mIg )

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

  7. H chain V region (,,,,) (Ag-biding site) L chain κ/λ (2:1) C region  H2L2 2 region Monomer of Ig hinge region

  8. Ag-biding site ---made up of VH and VL (HVR/CDR) HVR1/CDR1 FR1 FR2 HVR2/CDR2 HVR3/CDR3 FR3 FR4 HVR (hyper-variable region) CDR(complementarity determining region) FR (framework region)

  9. 2. Domain of Ig IgG VH/VL --- Ag-binding site (HVR/CDR) CH1/CL ---genetic marker of allotype CH2--- complement C1q binding site (CH3 of IgM) CH3,4--- binding to FcR on surface of cells(CH2, 3 of IgE binding to FcR) 19

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

  11. 4. Joining chain ＆ secretory piece A.Joining chain B.Secretory piece (SP) or secretory component (SC) (H2L2)2 J dimer (H2L2)5 J pentamer n(H2L2)n(monomer) (H2L2)nJ polymer J chain ---保护SIgA并介导IgA分泌到粘膜表面 C.Secretory IgA: (H2L2)2-SC-J

  12. 五类免疫球蛋白结构的异同 CH4 CH4 J chain J chain SC

  13. 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 通过胎盘 中和作用 2. C region activate complement binding to FcR on surface of cells transfer across placenta (IgG) 被动免疫 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

  14. Antibody-dependent cell -mediated cytotoxicity(ADCC) (抗体依赖的细胞介导的细胞毒作用) IgG Ag Ag (Ab包被的靶细胞) ADCC--- 指IgG类抗体与靶细胞表面抗原特异性结合后，表达IgG FcR的效应细胞(NK细胞、巨噬细胞和中性粒细胞) 可通过与靶细胞表面IgG的Fc段结合，而直接杀伤被抗体包被 的靶细胞

  15. 1.IgG:H2L2, IgG1 to IgG4 ---含量最多,免疫防御最重要;新生儿抗感染重要;用于紧急预防 2. IgM: (H2L2)5J, pentamer ---分子量最大, 血管内抗感染的主要抗体;最早合成和分泌(早期诊断和宫内感染指标); mIgM是BCR(单体) 3. IgA : monomer or dimer (secretory IgA,SIgA) Ⅳ.Characteristics and Functions of 5 Ig Classes ---分泌型IgA粘膜局部抗感染重要;婴儿从初乳可获得SIgA 4. IgD : monomer (H2L2) ---mIgD是BCR和B细胞成熟标志 5.IgE : monomer (H2L2) ---血中含量最少;介导Ⅰ型超敏反应

  16. Ⅴ.Monoclonal Antibody 1.Polyclonal antibody(pAb) ---含多个抗原表位的抗原免疫动物，可刺激体内多个B细胞克隆产生针对多种抗原表位的抗体，这种含有多种抗体的混合物，称为多克隆抗体 2.Monoclonal antibody(mAb) A.Conception B. Characteristics ---由针对(或识别)单一种抗原表位的B细胞克隆产生的同源抗体,称为单克隆抗体 ---高效价、高纯度、高特异性、低成本

  17. Immunoglobulin Superfamily A.Conception B.Structure 1.Conception and structure of IgSF 一类具有IgV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 2.Functions of IgSF A.Recognize Ag B.Interaction between cells (TCR,BCR) (CD4/CD8- -MHC; CD28-B7;LFA-ICAM) C.Transmit signal (CD3;Ig/Ig)

  18. p106 *Diversity and structure of BCR gene 1.Structure of BCR gene V region--- H: V,D and J L: V and J V region C region (14) VDJ连接成一个连续的DNA,编码V区 C region--- H: C, C ,C  … L:C, C (2) (22) p106 （四个J-C 对）

  19. 2.Diversity and Rearrangement of BCR gene •Rearrangement of H chain D2 joins with JH2 VH1 joins with D2JH2 •Diversity transcription *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 VH joins with C or C translation H chain

  20. p114 *Class switch of Ig 5’ C基因的5’端一段重复性DNA序列,称为转换区(switch region) IgM→IgG3? VDJ-C →IgM C,C VDJ-C3→→IgG3 •仅C区转换 •抗原特异性不变 IgM→其他类别或亚类Ig的现象,称为类别转换或同种型转换

  21. p114 *BCR & secreted Ig 编码C末端的疏水性跨膜区和胞浆区 (不含疏水性氨基酸) SIg mIg

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