Allergen Immunotherapy - Mechanism of Therapeutic Action

Mechanism of Therapeutic Action

The immune system of allergy affected individuals, for reasons not fully understood, misinterprets a usually innocuous substance as a disease agent and begins producing a type of antibody against it, called immunoglobulin E (IgE). This is called the 'primary antibody response.' The IgE produced during this response binds to basophils in the bloodstream and to a similar type of cell called mast cells in the tissues. When the person again encounters the allergen, it binds to the IgE that has already attached to basophils and mast cells, causing release of histamine, prostaglandins, and leukotrienes, producing inflammation of the surrounding tissues, and bringing about the familiar allergic symptoms.

Even the most allergic individual can tolerate minuscule amounts of an allergen without experiencing symptoms. Immunotherapy commences with the subcutaneous injection of a tiny amount of offending allergen, and gradually increases the dose until the individual's immune system is essentially 'retrained' to tolerate exposure without producing an allergic response. This process is also known as specific immunotherapy.

Immunotherapy via repeated exposure to a specific allergen via either sublingual or subcutaneous route leads to a desensitisation to the allergen and thus a reduction in allergic symptomatology and use of symptomatic based treatments. The exact mechanism is not fully understood but it is accepted that immunotherapy causes modification of the immune system. This modification leads to changes in IgE synthesis and the production of IgE blocking antibodies which thus reduces the immune system's allergic response to specific allergens. There is also an increase in conversion of Th2 to regulatory T cells. At a molecular level, part of the therapeutic mechanism relies on the preferential induction of allergen-specific IgG to neutralize the allergen in place of allergen-specific IgE. In bee or wasp venom immunotherapy, immunoglobulin subclass IgG4 has been considered to be particularly important, where IL-10 make the B cells to switch the produced immunoglobulin class from IgE to IgG4. It has been revealed that the mechanism of this immunotherapy consists of some more other components. They include increased production of IL-10 which acts on Th2 or mast cells to become anergic and suppresses Th2 not to release cytokines and prevent histamine from being secreted. It was indicated that osteopontin produced by CD14+ cells induced IL-12 in antigen presenting cells to activate Th1. It was recently shown that a progressive expansion of circulating regulatory T cells was made during venom immunotherapy.