Cutaneous immunology: From mast cell to eosinophil

July 1, 2005

One of the new things that researchers have uncovered is that the allergic response is actually a triple-phase reaction.

Researchers are developing a better understanding of allergic inflammation, and the skin is an important organ for defining the process.

This greater understanding focuses on factors, including that of the allergy protein IgE, which play important roles in the complex process of allergic inflammation, according to dermatologist Kristin M. Leiferman, M.D., professor of dermatology, department of dermatology, University of Utah, Salt Lake City.

"In models of allergic response, IgE stimulates or interacts with specific cells that are known to be mediators of the process," she says.

"When IgE is exposed to something that it has developed the ability to bind to an allergen it causes activation of mast cells and basophils. A cascade of allergic inflammation then produces an allergic response," Dr. Leiferman explains. "One of the beauties of skin is that it is an organ that is very accessible. It is very expressive. You can use the skin as a model for inflammation for other areas - the nasal track, lung, even the digestive tract."

Mast cells, basophils, eosinophils When activated, mast cells, which are resident cells of loose connective tissue in the skin and other areas, secrete a heterogeneous group of mediators. These include vasoactive substances, chemotactic factors, proteolytic enzymes, cytokines and proteoglycans, according to Dr. Leiferman.

Mast cells in disease have been associated with hypersensitivity reactions, including atopic dermatitis, urticaria and angioedema, as well as contact dermatitis, irritant inflammatory reactions, among others, and are notably present in urticaria pigmentosa and other types of mastocytosis.

Although scientists have yet to uncover their role in disease, basophils are important cells in making certain proteins that influence the inflammation of the skin, which is associated with allergies.

Basophils are associated with ectoparasite resistance, cutaneous basophil hypersensitivity or contact dermatitis (poison ivy), hypersensitivity, drug reactions and myeloproliferative diseases, according to Dr. Leiferman.

Researchers do not believe that there is direct communication between IgE and eosinophils through receptors in most circumstances, Dr. Leiferman says.

"Unlike mast cells and basophils, the eosinophil does not appear to have IgE receptors. However, some of the chemicals and molecules that are produced by cells and that stimulate IgE production also influence eosinophil production and eosinophil activity. So, it is a cell that is importantly drawn into the whole allergic reactivity, but it is not one that has a real direct link, as do mast cells and basophils to the allergy antibody, IgE. Activated eosinophils have a variety of phlogistic activities that implicate it in the allergic inflammatory process."

The involvement of eosinophils has been characterized in eczematoid dermatitis, urticaria and edema, blistering disorders and vasculitis.

Defining allergic reaction Dr. Leiferman defines the allergic reaction as an IgE-mediated inflammatory response to an allergen brought about by various cells and cell products.

The cardinal features are IgE synthesis, IgE dependent mast cell activation, eosinophil infiltration and activation, and T-lymphocyte infiltration and activation. Clinical manifestations in the skin include itch, erythema and edema.

"Allergic diseases have increased in prevalence dramatically over the last few decades," she says. "There are a number of theories about why that is happening. One popular theory is the 'hygiene hypothesis,' involving the diminished exposure to endotoxin, a reduction of infectious diseases that modify the immune system, and a lack of parasites in the modern society that may allow a once-protective mechanism to cause disease."

The allergic response starts with lymphocyte deviation to the TH2 (T-helper cell 2) cytokines, inducing IgE production. IgE that recognizes specific allergens binds to receptors on mast cells and basophils. When exposure to allergen occurs, bridging of IgE on mast cells and or basophils activates the allergic response.

"What happens in the allergic reaction is that it actually stimulates the production or the development of more of these white blood cells, called TH2 lymphocytes; TH2-type cells secrete specialized proteins, or cytokines, that continue to contribute to the allergic reaction by inducing more IgE production. It is a vicious circle," Dr. Leiferman says.