Allergy and the Immune System

Nasal, ocular and respiratory allergies are quite easy to understand from a symptom point of view, but it is not always appreciated that symptoms represent the end result of a complex number of  events affecting the immune system. Allergies are caused by a loss of regulation in a specific arm of the immune system. Our immune system is designed to protect us from infection, but a specific part of this system goes "haywire" in people with allergies. The first concept to understand is the allergen, which is defined as any substance that can activate, be recognized or turn-on the immune response.   A non-allergic person's immune system does not "see" the substance, and does not recognize the allergen. Examples of common allergens are drugs, dust mites, pollens, mold spores and animal dander. Why one person's immune system is programmed to  recognize substances that are normally harmless to most people is not completely understood. We do know there is a strong inherited tendency to develop allergies, meaning that allergies are influenced by genes and run in families.

The first step in the allergic response occurs when the allergen comes in contact with a body surface. The key substance that recognizes the allergen when it contacts a body surface is an antibody known as IgE. This antibody is normally present in minute amounts in the bloodstream and tissues of normal people. Because so little exists in normal people, progress was very slow towards its discovery. Although it was known that something in the blood caused allergies for about one- hundred years, and allergic reactions could be transferred to non-allergic people, IgE was not identified as the responsible substance until the 1960's. In allergic individuals, IgE  is a component of the tissues lining the eyes, nose, lung and intestinal tract. IgG Antibodies are normally produced by the body to fight and kill invading organisms. In the case of IgE, it is only produced with invasive parasite infections such as schistosomiasis or trichinosis, which are common in under-developed parts of the world. Production is therefore restricted and tightly controlled. People with allergies have lost the  ability to regulate production of IgE, and the immune system starts reacting to common substances in the environment by the exuberant production of IgE.

IgE by itself is unable to start an allergic reaction. Instead, it needs help from a tissue cell known as a mast cell. IgE sits on the mast cell until it sees an allergen. Each IgE has a very specific substance that it can recognize. For example, IgE that can bind to birch pollen will not bind to dust mite allergens. Thus one may be allergic to dogs and not cats, or vice versa.  If the IgE can bind or "sees"  the allergen, it activates the mast cell. This activation causes the mast cell to release a large number of chemical substances as well as to begin manufacturing new ones. These chemicals produce the symptoms of an allergic response. Thus surrounding tissues swell, blood flow  increases, mucous production increases, itching occurs and contraction of muscles surrounding the airways causes wheezing. Symptoms produced include nasal congestion, sneezing, runny nose, eye irritation, wheezing and shortness of breath.

The most important chemical mediator released during an allergic reaction is histamine. Hence, anti-histamines have widespread application to allergic diseases. Other substances released hours after the initial reaction include leukotrienes, prostaglandins, enzymes, lipids and neurotransmitters. This second wave release of chemical mediators is called the late phase response.  Corticosteroids have little effect on histamine release but do affect the late phase response. Allergic rhinitis resemble an acute response and is controllable with antihistamines. Asthma however is more typical of a chronic late phase response and is helped by corticosteroids.

Thus, there are two phases to an allergic reaction. An immediate phase, mostly mediated by histamine and a late-phase response 6-12 hours later mediated by newly produced chemical substances. Treatment of chronic allergies therefore requires both anti-histamines for the early response and anti-inflammatory drugs such as corticosteroids for the delayed response.

Why allergic diseases have become more frequent is currently under debate. One theory suspects that childhood immunization has altered the way our immune system responds to the environment. In this model  natural childhood viral infections have a protective effect against the development of allergies. Since we no longer acquire these infections, we are not protected against allergies.

Another theory proposes that the relative cleanliness of modern homes prevents exposure to bacterial products that stimulate the immune system. This theory called the "hygiene hypothesis" was induced from the observation that children growing up on farms are less frequently affected than other children by allergies. These environments are notable for a heavy load of mold and bacteria from decaying organic matter and animal waste.

Allergic Contact Dermatitis

Skin allergies, especially allergic contact dermatitis, occur by a different mechanism.  Antibodies play no role in starting this type allergic response. However, it has been demonstrated that animals with a complete lack of IgE do not develop allergic contact dermatitis. The initial phase of  the allergic reaction begins with a cell called a lymphocyte. This is specialized type of white blood cell that is also found in tissues. The allergy causing substance  is usually a small molecule, such as a nickel salt, that chemically combines with proteins in the skin. At this point, it can be recognized by lymphocytes, which which are then activated and call other lymphocytes into the area, amplifying the allergic response. These lymphocytes also release other chemicals that cause inflammation in the surrounding tissues. These "chemokines" cause dilatation of blood vessels, leakage of blood proteins, swelling oozing and blistering. Release of histamine is a secondary response. Steroid drugs therefore play a more important role in this type of allergic reaction than anti-histamines. Steroids decrease the number of circulating lymphocytes and the production of inflammatory chemokines and are the most useful agents for treatment.