NOBEL PRIZES FOR ANTIBODY RESEARCH 1901 von Bering

NOBEL PRIZES FOR ANTIBODY RESEARCH 1901 von Bering 1908 Ehrlich & Metchnikoff Edelman & Poter 1972 1977 Yalow 1984 Koler, Milstein & Jerne 1987 Tonegawa Serum therapy antitoxin Chemical structure of Ab Radioimmunoassay Monoclonal Ab Ig gene rearrangement

Discovery of Ab 抗体的发现 1890: von Behring and Kitasato -ANTIBODIES in the serum of vaccinated individual bind to pathogens Emil von Behring 1854 - 1917, Nobel Prize in 1901 for demonstrating that circulating antitoxins against diphtheria and tetanus toxins conferred immunity.

Immune sera Normal sera

Ⅰ. Basic Immunoglobulin Structure Ig的基本结构

重链和轻链 25 k. D 214 aa 1)重链Heavy chain: 5 Classes , , . Ig. A, Ig. G, Ig. M, Ig. D, Ig. E 50 -75 k. D 2) 轻链light chain: 2 types: : =2: 1 450 -550 aa

决定簇互补区( Complementarity determining region, CDR), 即V区中的高变区(Hyperviable region），直接与抗原表 位接触结合的区域 V区 CDR 1 CDR 2 29 -31 49 -58 FR CDR 3 91 -98

抗体分子的水解片段 木瓜蛋白酶 （papain） 2 Fab，1 Fc N VH N CH 1 VL CL 胃蛋白酶 （pepsin） F(ab’)2, p. Fc S-S -S-S- S-S CH 2 H CH 3 C L

Gerald Edelman 1929 -- Rodney Porter 1917 -1985 Nobel Prize in 1972

Summary小结 Varible region NH 3+ VH VL CH 1 Fab CL Hinge region CH 2 CH 3 Constant region CH 4 COO– Fc 1. A four polypeptide chains basic unit composed of two identical light chains and two identical heavy chains , held by disulfide bonds(二硫键）。 2. Y-shape structure, symmetric. 3. –NH 2 terminal, -COOH terminal 4. variable & constant regions. 5. domains: polypeptide chains folded by disulfide bonds into globular regions.

Ⅲ. FUNCTIONS OF ANTIBODY 抗体的功能 Ⅰ

活化补体 C 1 qr 2 s 2 C 1 r C 1 s C 1 q No activation Activation

调理作用 O P S O N I Z A T ion

抗体依赖细胞介导的细胞毒作用 效应细胞 Ab Fc R 靶细胞 Target cell ADCC A form of nonspecific cytotoxic cell-mediated reaction in which an effector kills an antibody-coated target cell, presumably by recognition of the Fc region of the cellbound antibody through an Fc receptor presented on the effector cell (e. g. , NK cells, neutrophils, Macrophages).

Ⅳ. Properties & Biological Activities of Five Classes of Immunoglobulins 五类Ig的特性与功能 Ⅰ

Ig. E Ⅰ structure Monomer Extra domain: CH 4

Ⅴ. 人 制备抗体 多克隆抗体Polyclonal antibody, p. Ab 单克隆抗体Monoclonal antibodies, m. Ab 基因 程抗体Genetic engineering antibody

单克隆抗体制备 Crotalus atrox Remove spleen Cell fusion Collect venom Immunize BALB/c mice purity venom Check cells for production of Ab Expend and grow cells ELISA Myeloma cells Expend postive cells