What causes some people to sneeze and wheeze every time they step out into the spring air, while others suffer no ill effects? We can answer this question by examining what occurs in the tissues of the allergic individual that does not occur in the normal person. What is not as easy to answer is the question of why allergy is so common, affecting over 40% of the world’s population. What useful function, if any, can it possibly serve? See 16.1 Making Connections for some possible explanations.
In general, allergies develop in stages (process figure 1). The initial encounter with an allergen provides a sensitizing dose that primes the immune system for a subsequent encounter with that allergen but generally elicits no signs or symptoms. The memory cells and immunoglobulin produced during this encounter are then ready to react with a subsequent provocative dose of the same allergen. It is this dose that precipitates the first signs and symptoms that an allergy exists. Despite numerous anecdotal reports of people showing an allergy upon first contact with an allergen, it is generally believed that these individuals unknowingly had contact at some previous time. Fetal exposure to allergens from the mother’s bloodstream is one possibility, and foods can be a prime source of “hidden” allergens such as penicillin.
Fig1. A schematic view of cellular reactions during the allergic response. (a) Sensitization (initial contact with sensitizing dose), includes steps 1–6. (b) Provocation (later contacts with provocative dose), steps 7–10.
The Physiology of IgE-Mediated Allergies
During primary contact and sensitization, the allergen penetrates the portal of entry (process figure 16.3, steps 1–6). When large particles such as pollen grains, hair, and spores encounter a moist membrane, they are first captured by dendritic cells, which process the allergen and present it to T helper cells in the lymph nodes. Here, the T cells interact with clones of B cells, which they activate to respond to the specific allergen. This causes proliferation of plasma cells, following a sequence similar to the typical immune response to an antigen. These plasma cells produce immunoglobulin E (IgE), the antibody of allergy. IgE is different from other immunoglobulins in having an Fc region with great affinity for mast cells and basophils. The binding of IgE to these cells in the tissues sets the scene for the reactions that occur upon repeated exposure to the same allergen (process figure 1, steps 7–10).
The Role of Mast Cells and Basophils
The most important characteristics of mast cells and basophils relating to their roles in allergy are these:
1. Their ubiquitous location in tissues. Mast cells are located in the connective tissue of virtually all organs, but particularly high concentrations exist in the lungs, skin, gastrointestinal tract, and genitourinary tract. Basophils circulate in the blood but mi grate readily into tissues.
2. Their capacity to bind IgE during sensitization (process figure 1). Each cell carries 30,000 to 100,000 cell receptors that bind 10,000 to 40,000 IgE antibodies.
3. Their cytoplasmic granules (secretory vesicles), which contain physiologically active cytokines (histamine, serotonin).
4. Their tendency to degranulate (process figure 1 and figure 2) or release the contents of the granules into the tissues when triggered by a specific allergen through the IgE bound to them.
Let us now see what occurs when sensitized cells are challenged with allergen a second time.
Fig4. The spectrum of reactions to inflammatory cytokines released by mast cells and the common symptoms they elicit in target tissues and organs. Note the extensive overlapping effects.
The Provocative Contact with Allergen
After sensitization, the IgE-primed mast cells can remain in the tis sues for years. Even after long periods without contact, a person can retain the capacity to react immediately upon reexposure. The next time allergen molecules contact these sensitized cells, they bind across adjacent receptors and stimulate degranulation. As chemical mediators are released, they diffuse into the tissues and bloodstream. Cytokines give rise to numerous local and systemic reactions, many of which appear quite rapidly (process figure 1, step 10). Thus, the symptoms of allergy are caused, not by the direct action of allergen on tissues, but by the physiological effects of mast cell mediators on target organs.
