Chapter 4 ANTIBODY STRUCTURE AND FUNCTION

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1 Chapter 4 ANTIBODY STRUCTURE AND FUNCTION

2 Different way to depict an Ig molecule Y

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5 In both the heavy and light chain variable regions there is variability at every position and there are hypervariable regions

6 CDR: complementarity-determining regions

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8 The antigen binding site is made-up of both heavy and light chain CDRs

9 Antibodies contact epitopes or antigenic determinants This antigen is a protein. This part of the protein is the epitope for this antibody. *The epitope is small (~6 amino acids or ~6 sugars) or a small part of a larger antigen. An antigen is the whole molecule (or cell) bound by the antibody. Also, the antigen could be an isolated epitope. Immunogens induce immune response and are the target of the induced response. Immunogens are antigens but not all antigens are immunogens.

10 Epitopes are conformational discontinuous or continuous This antibody binds aa 81-87; it binds a continuous epitope This antibody binds aa 34-40; it binds a continuous epitope This antibody binds aa and 85-88; it binds a conformational epitope This antibody binds aa and 61-64; it binds a conformational epitope

11 How an antibody can exhibit binding with two different epitopes

12 Five major classes of secreted antibody

13 Greek letters are used to name the heavy and light chain constant regions For example; g, m, a, d, e for the heavy chains k, l for the light chains) The heavy chain determines the class of the Ig, thus If the heavy chain is g the class is IgG (and g1 for IgG1, etc.) If the heavy chain is m the class is IgM If the heavy chain is a the class is IgA If the heavy chain is d the class is IgD If the heavy chain is e the class is IgE?? a l k d g A: IgA l IgG IgD Different heavy chains provide different functions and distribution; there is no known difference in function for k and l

14 I. IgG Structure: Monomer Immunoglobulin Classes Percentage serum antibodies: 80% heavy chain is g the class is IgG Subclass IgG1, IgG2, IgG3, IgG4 Location: Blood, lymph, intestine Half-life in serum: 23 days Complement Fixation: Yes Placental Transfer: Yes Known Functions: 1. Agglutination and formation of precipitate >>Enhances phagocytosis 2. passage through the placenta enabling the mother to transfer her immunity to the fetus 3. Opsonization >>Enhances phagocytosis (Fc receptor on phagocytic cells) 4. Antibody-dependent, cell-mediated cytotoxicity (ADCC) by NK cells 5. Activation of complement 6. Neutralization toxins and viruses 7. Immobilization of bacteria

15 II. IgM Immunoglobulin Classes Structure: Pentamer Percentage serum antibodies: 5-10% Location: Blood, lymph, B cell surface (monomer) Half-life in serum: 5 days Complement Fixation: Yes Placental Transfer: No Known Functions: First antibodies produced during an infection. Effective against microbes and agglutinating antigens.

16 III. IgA Structure: Dimer Immunoglobulin Classes Percentage serum antibodies: 10-15% Location: Secretions (tears, saliva, intestine, milk), blood and lymph. Half-life in serum: 6 days Complement Fixation: No Placental Transfer: No Known Functions: Localized protection of mucosal surfaces.

17 IV. IgD Immunoglobulin Classes Structure: Monomer Percentage serum antibodies: 0.2% Location: B-cell surface, blood, and lymph Half-life in serum: 3 days Complement Fixation: No Placental Transfer: No Known Functions: In serum function is unknown. On B cell surface, initiate immune response.

18 V. IgE Immunoglobulin Classes Structure: Monomer Percentage serum antibodies: 0.002% Location: Bound to mast cells and basophils throughout body. Blood. Half-life in serum: 2 days Complement Fixation: No Placental Transfer: No Known Functions: Allergic reactions. Possibly lysis of worms.

19 Recycling of IgG using the protector receptor

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22 Immunoglobulin superfamily

23 Antigen-antibody complexes are held together by non-covalent forces (therefore, antigen binding by antibody is reversible)

24 Antigen recognition by the TCR (soluble) BCR or membrane Ig or surface Ig B cell Note the transmembrane and cytoplasmic amino acids here but they are absent on the soluble forms of Igs

25 The TCR There is also a TCR made of a g and d chain (the gd TCR)