The mechanism of anaphylaxis antibodies

The agent triggering an anaphylactic reaction is known as the antigen. A molecule's ability to act as an antigen is called its immunogenicity. Antigens are classically large molecules which stimulate an immune response on their own, or smaller compounds (haptens) that bind to proteins prior to producing a reaction. Most polypeptides can act as complete antigens; however, compounds such as suxamethonium, which have two antigenic groups an appropriate distance apart for bridging cell-bound IgE molecules, may be able to act as antigens without first binding to protein. In some circumstances a metabolic breakdown product of the parent molecule may be the antigenic component.

Antibodies are formed when antigens stimulate B lymphocytes to form plasma cells which secrete protein macromolecules that have an ability to bind to the antigen that stimulated their production, usually rendering the antigen harmless. Antigen-antibody complexes form rapidly, for example after food ingestion, and are rapidly cleared from plasma. If they persist and bridge cell-bound antibodies, or the complex binds to cell walls, allergic symptoms occur, leading to a series of syndromes ranging from minor to life threatening. The antibodies formed by plasma cells are measured as immunoglobulins. The immunoglobulins may be bound to cells, exist free in blood, or be released into secretory systems. They are Y-shaped molecules with Fab (antibody binding) and Fc (cell binding) segments. Five classes are recognized: IgA, IgD, IgE, IgG, and IgM.

IgG has a molecular weight of 150 kDa. When the Fab site combines with the antigen, the Fc region becomes complement activating. IgG4 does not bind complement but binds to mast cells, while IgG and IgG3 readily activate complement. IgG2 is a less active activator of complement. IgG diffuses more readily than other antibodies; it binds to bacteria and adheres to phagocytic cells. IgG4 probably also acts as a reaginic antibody. IgG complement-dependent antibodies against protamine and cremaphor have been found in the serum of reactors. It is possible that clinical anaphylaxis to cremaphor-based drugs, which usually shows evidence of classical pathway activation, is mediated by IgG antibodies. IgG4 antibodies can be detected by skin tests.

IgE is responsible for the majority of true anaphylaxis. Very small concentrations exist in serum, and the majority of the immunoglobulin is bound to mast cells. The physiological role of IgE is not known. Bridging of IgE molecules by antigen leads to anaphylactic mediator release. Elevated levels of IgE are usually found in patients with a history of allergy, atopy, or asthma.

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Coping with Asthma

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