Immunoglobulin isotypes

The antigen specificity of antibodies is mediated by the two antigen-binding sites, while the differing Fc regions of the various immunoglobulin isotypes engage differing effector mechanisms. Monomeric IgM and IgD act as B-cell surface antigen-specific receptors. The affinity of each IgM antigen-binding site tends to be low; however, IgM in serum usually polymerizes into a pentamer with ten antigen-binding sites, which give the antibody high binding strength.

IgM dominates the initial humoral immune response; however, IgG and IgA predominate later, although IgE is prominent during an allergic response. This process is known as isotype switching and is the consequence of DNA

Antigen-binding site Antigen-binding site

Antigen-binding site Antigen-binding site

  1. 1.1. Schematic representation of an IgG molecule. The two domains of each of the two light chains are termed VL and CL. The four domains of each of the two heavy chains are termed VH, CH1, CH2 and CH3. The amino terminal (dark) domain of each chain is the variable region and it is the tips of these regions that form the two antigen-binding sites of the molecule.
  2. 1.1. Schematic representation of an IgG molecule. The two domains of each of the two light chains are termed VL and CL. The four domains of each of the two heavy chains are termed VH, CH1, CH2 and CH3. The amino terminal (dark) domain of each chain is the variable region and it is the tips of these regions that form the two antigen-binding sites of the molecule.

rearrangements in the genes encoding for the C (but not the V) regions of the heavy chains (Stavnezer, 1996). Isotype switching results in differing classes of antibodies with differing functional properties, although antigen specificity remains constant. Isotype switching is dependent on T-cells and their secretion of cytokines, with interleukin-4 (IL-4) inducing B-cell switching to IgE; this is antagonized by interferon-7 (IFN-7) (Pene et al., 1988). Switching to IgA is promoted by transforming growth factor-p (TGF-p), in combination with IL-10 (Defrance et al., 1992). In addition to isotype switching, as the humoral immune response matures, point mutations in the immunoglobulin V-region genes occur. A T-cell-dependent process, known as affinity maturation, selects those B-cells with point mutations producing antibodies with an increased affinity for the stimulating antigen. Consequently, as the humoral immune response progresses, the affinity and specificity of the antibodies increase and the resulting memory cells provide highly effective protection against reinfection by the same microorganism (Neuberger and Milstein, 1995).

IgG antibodies are monomeric and are further subdivided into IgG1, IgG2, IgG3 and IgG4, with IgGx being found in the greatest quantities in serum. IgGx and IgG3 are transferred across the placenta to the fetus. IgA circulates in the bloodstream but, of more functional importance, IgA is secreted across mucous membranes and is found in intestinal and bronchial secretions, tears and breast milk. Circulating IgA is monomeric, while secreted IgA polymerizes into dimers; polymerization is required for transport across epithelia. IgA is subdivided into IgA1 and IgA2. IgE is the principal antibody isotype involved in the immune response to parasites and in allergic reactions. The € heavy chains possess an extra constant heavy-chain (Ch) domain and the Fc component binds with high affinity to the Fc€R1 receptor found on the surface membranes of mast cells, basophils and activated eosinophils.

How To Bolster Your Immune System

How To Bolster Your Immune System

All Natural Immune Boosters Proven To Fight Infection, Disease And More. Discover A Natural, Safe Effective Way To Boost Your Immune System Using Ingredients From Your Kitchen Cupboard. The only common sense, no holds barred guide to hit the market today no gimmicks, no pills, just old fashioned common sense remedies to cure colds, influenza, viral infections and more.

Get My Free Audio Book


Post a comment