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Antibodies

Antibodies. Contents. Ⅰ Structure Ⅱ Diversity Ⅲ Function Ⅳ Characteristic and Function of various classes of antibodies Ⅴ Artificial antibodies. Basic concepts ----S timulation of B cells with antigen s leads to differentiation of the B cell s to plasma cells.

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Antibodies

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  1. Antibodies

  2. Contents Ⅰ Structure Ⅱ Diversity Ⅲ Function Ⅳ Characteristic and Function of various classes of antibodies Ⅴ Artificial antibodies

  3. Basic concepts ----Stimulation of B cells with antigens leads to differentiation of the B cells to plasma cells. ----Antibodies are glycoproteins secreted by plasma cells. ----Antibodies can specifically bind to the corresponding antigens. ----Antibodiesare secreted into the serum to make up the circulating antibody pool. ----Antibodies are also called immunoglobulins (Ig). ----secretory Ig; membrane Ig

  4. The structure of immunoglobulins 1. Basic structure (1) a common structure of fourpeptide chains H2L2 linked by disulfide bonds: twoidentical light (L) chains, polypeptides of about 25,000molecular weight, and two identical heavy (H) chains, largerpolypeptides of molecular weight 50,000 or more Heavy chain: 5 types (isotype: a, g,m,d,e) Light chain: 2 types (k,l)

  5. 2. Three functional regions Variable region, VH/VL, Fv: to bind to the antigens VH and VL: hypervariable regions, HVR----antigenbindingsites----complementarity-determining regions, CDR framework regions, FR1-4 Constant region, CH/CL Hinge region

  6. Functional Regions of Immunoglobulins

  7. 3. enzyme digestion Papain: Fab, Fc Pepsin: F(ab’)2, pFc’ The enzyme digestion products of Immunoglobulins

  8. Antibody Classes and Antigenic Determinants on Ig 1. Classes and Types Class: Antigenicity of the heavy-chain constantregion----IgG, IgA, IgM, IgD, IgE Subclass: Antigenicity of the heavy-chain/number and location of disulfide bonds----IgG1-4 Type: Antigenicity of the light-chain constantregion----k, l Subtype: different arrangement of aa in the light-chain constantregion----l1~4

  9. 2. Antigenic Determinants on Ig Isotype: constant-region determinants----non-genetic sign Allotype: different alleles----genetic sign Idiotype, Id: Idiotope→Anti-Id Isotype Allotype Idiotype

  10. 3. Accessory structures (1) J chain (Joining chain) (2) Secretory piece, SP 4. Domain (1) Compact dimensional globes formed by intrachain disulfide bond in Ig molecule (V/C/H/L) (2) b-sheet, b-barrel, immunoglobulin fold (3) CDRs(complementarity-determining regions, hypervariable regions), FRs(Framework regions)

  11. Diagram of an immunoglobulin light chain depicting the immunoglobulin-fold structure of its variable and constant domains.

  12. General structures of the five major classes of secreted antibody.

  13. Main Characteristic and Biological Functions of Ig 1. Main Functions (1) specifically bind to the corresponding antigens: Fv (2) activate complements (3) bind to FcR: opsonization allergic reactions antibody-dependent cell-mediated cytotoxicity (ADCC) (4) cross the placenta and the mucosal surfaces (5) regulate immune response

  14. Figure 1-24

  15. CDR of Ab binds to the epitope of Ag.

  16. Opsonization mediated by antibodies

  17. antibody-dependent cell-mediated cytotoxicity (ADCC) mediated by NK cells

  18. 2. Characteristics and functions of various classes of antibodies (1) IgG four subclasses, widely distributed, the most abundant class in serum, the only class that can cross the placenta (2) IgM five monomer subunits linked by J chain, the first class produced in a primary response to an Ag, diagnostic sign for intrauterus and recent infection (3) IgA monomer: serum; dimer: external secretions (4) IgD low levels, the major membrane-bound Ig expressed by mature B cells (5) IgE extremely low average serum concentration, cytophil, hypersensitivity/antiparasitic defense

  19. mIgM mIgD immature B cells mature B cells activated/memory B cells

  20. Production of Antibodies 1. polyclonal antibody, PcAb 2. monoclonal antibody, McAb 3. engineering antibody antibodies produced by using DNA recombination technique and genetic engineering means including human-mouse chimeric Abs, reshaped Abs, bispecific and bifunctional Abs, small molecule Abs etc

  21. Production of Polyclonal Antiserum

  22. Humanization（Chimeric/Reshaped Antibody)

  23. ***the structure and key biological function of immunoglobulins ** antibody diversity ** the concepts and the characteristics about monoclonal antibodies * the concepts and the characteristics about production of monoclonal antibodies

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