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Immune Hypersensitivity

The original concept of allergy included all immune-mediated diseases and the term allergy was interchangeable with the term "hypersensitivity." In one textbook of clinical immunology allergy is defined: “The original definition of allergy (Von Pirquet, 1906) was a specifically changed reactivity of the host to an agent on the second or subsequent occasions. This covers a whole spectrum of immune responses, both protective and harmful. However, more recently, the term allergy had been restricted to the latter and is now synonymous with type 1 hypersensitivity. This rigid definition is too narrow to cover the range of conditions seen by allergists in clinical practice. It is likely that all four types of hypersensitivity are involved in various allergic diseases and indistinguishable reactions can sometimes be produced without immunological involvement."

Four mechanisms of hypersensitivity are:

Type 1 or immediate hypersensitivity is IgE-mediated or common allergy.

Type 2 or cytotoxic reactions mediated by antibody, complement, and/or cellular mechanisms. The target in type II reactions is a cell membrane and cellular damage or death is the result.

Type 3 mechanisms involve antibodies forming immune complexes with antigen. Circulating complexes activate complement, attach to red blood cells that are removed by phagocytosis in the spleen, or leave the circulation and trigger inflammation in tissue spaces (Arthus reaction), or are phagocytosed by macrophages in tissue spaces which present antigen, release cytokines and activate T-cells.

Type 4 are cell-mediated reactions take 12 or more hours to develop and are based on antigen, T-cell interaction. Inflammation is the basic tissue expression.

Allergy can be thought of as hypersensitivity disorders with external causes. Substances that trigger allergic responses are antigens. These are often proteins that can be found in air, food and water. Airborne antigens such as plant pollens or house dust are well known. Other airborne antigens and food antigens are less obvious. New and foreign substances introduced to the body such as drugs and herbs usually cause delayed allergic reactions.

When investigating the origin of hypersensitivity diseases, food materials should be given priority consideration since that are the biggest chunk of the environment to get inside human bodies. If the term "food allergy" refers to all interactions between molecules derived from the food supply and the immune system, then many hypersensitivity disorders fall into the category of food allergy. The spectrum of manifestations of food allergy can only be understood if different patterns of food allergy are allowed.

The first distinction that recurs in the allergy literature is between immediate and delayed patterns of allergic reactivity that correspond to IgE-mediated allergy and non-IgE mediated responses.

Many authors refer to the original four categories of immune-mediated injury defined by Gell and Coombs. The concept of four mechanisms is just a starting point for understanding immune-mediated disease. These very complicated defense-injury sequences cause a variety of disease states.

The immediate or type 1 allergy pattern is easily recognized because it involves quick and dramatic symptoms. Hay fever is the most common type 1 allergy and can be diagnosed by allergy skin tests and by IgE antibody-antigen tests such as RAST or ELIZA.

Delayed patterns of allergy are not so obvious and generally go unrecognized. Allergy skin tests do not show this problem. Symptom onset is delayed many hours after exposure to the trigger. Allergic reactions to drugs such as penicillin and to foods involve delayed hypersensitivity.