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Paula M. Jardieu, Robert Shields and Gerald Nakamura
The Genentech Teaching Team

Do you have allergies? If you do, you are in good company. In the US, one in ten people suffer from some form of allergy. Allergic reactions range from life threatening as in the case of allergies to bee stings or penicillin to responses as mild as sneezing when you sniff a flower to which you are sensitive. Regardless of the severity, the underlying cause of most allergic reactions is the same.

An allergic reaction is triggered when the body's immune system over-reacts to the presence of something that is not usually found in the body. The allergen can get there by being eaten or inhaled, or by injection as may occur with an insect sting. Allergic reactions occur most commonly to pollen grains, dust, molds and foods. Allergic reactions can also occur to animal proteins such as those found on hair, fur, or dander, and to topical agents such as the oils found on poison ivy leaves.

When an allergic person is exposed to an allergen his or her B cells produce a special class of antibodies known as Immunoglobulin E, or IgE. These IgE molecules can readily bind to the allergen that caused their production - in other words they are "specific" for the original allergen. Specific IgE molecules travel through the blood and attach to receptors on the surface of "mast cells."

Once on the mast cell surface, allergen-specific IgE can remain for weeks or even months, always ready to bind to the original allergen. The next time the allergen enters the body, the allergic cascade begins and eventually results in the release of histamines from the mast cell. As annoying as the symptoms of alergy are, they do serve a purpose - they are an attempt by the body to wash away the offending allergen.

What are people allergic to? Pollen is the No. 1 allergen, or troublemaker maker for people with allergies. Breathing pollen results in "rhinitis" or what is more commonly called hay fever. Hay fever has nothing to do with hay and does not produce a fever, but in the 1800's this is the name doctors gave to this disorder and the name stuck. Allergies to pollen are so common that the relative severity of the allergy season is determined each year by the amount of pollen released by the grasses and weeds around the area in which you live. This figure is recorded as the daily "pollen count" and is published locally in newspapers and announced on the radio. In a bad season, the pollen count can increase dramatically - from 1000 grains of pollen per cubic meter of air (people breath about 10 cubic meters of air/day) to 8000 grains of pollen per cubic meter of air. Something to sneeze about!

Lots of other substances beside pollen can also provoke allergic responses. The most serious and difficult to avoid are found in the droppings of dust mites. Dust mites are microscopic insects which collect in house dust and survive on sloughed off flecks of human skin. Their droppings - each about the size of a pollen grain - are inhaled and can produce the same symptoms as pollen: wheezing, sneezing, coughing, and difficulty breathing. This happens because they also stimulate IgE production and mast cell release of histamine. Dust mite droppings are reported to be responsible for about 50% of the cases of asthma in children in this country.

Other allergens include molds and animal proteins. It is interesting to know that when people are allergic to their cats they are actually allergic to a protein in cat saliva. When a cat licks its hair and then sheds its hair around the house, you are exposed to the saliva on the hair and can develop allergic symptoms to the saliva. This connection between saliva, cat hair, and allergies was made by scientists who were able to raise cats that did not lick their coats. They compared the severity of cat allergies in people exposed to cats that licked their fur to people exposed to cats that were less fastidious. They found that it was the saliva proteins on the fur which were responsible for the allergy.

Food molecules can also act as allergens. Food allergies may be very severe and can lead to anaphylaxis. Anaphylaxis occurs because some allergens, including those found in peanuts and shellfish, can cause the mast cells to open fire with the equivalent of a semi-automatic release of all its ammunition at once. Such an "over-response" quickly leads to complete closure of the air passages and death by suffocation. Anaphylaxis can also occur in response to insect venoms.

Not all allergens work by inducing B cell IgE production and subsequent release of histamines by mast cells. Poison ivy and poison oak, for example, produce an oil which is absorbed through the skin. Once absorbed, the oil causes a T cell to release chemicals that cause inflammation and other allergic responses.

Why are some people allergic to their cats or to certain foods, while others have no adverse reactions to anything? This is an area of open debate and intense research. It is clear that some of the cause is genetic. People seem to inherit allergies, most often from their mothers. At least 3 genes are believed to be responsible for allergy, but only one putative gene has been identified. This gene produces a lymphocyte growth factor, known as interleukin 4 (IL-4), that is required for production of IgE. Overproduction of IL-4 leads to more IgE which, in turn, results in the well known wheezing and sneezing symptoms of allergy.

So how do we treat allergies? The most effective way is avoidance. Don't go near what you are allergic to if you can help it. If your cat makes you sneeze and you avoid your cat, you will stop sneezing since there is no cat saliva to cause IgE production. If you are allergic to pollen, take refuge in sealed, air conditioned building. There are extreme examples of individuals who believe they are hypersensitive to new classes of chemical allergens produced by the chemicals we use to manufacture everything from fabrics to perfume. Their solution is to place themselves in an extreme state of isolation and solitary confinement away from the world. It must be said however that these allergies may not be related to IgE.

When it isn't possible to avoid the allergen, doctors prescribe antihistamines. A major side effect of these drugs is that they can cause you to become very sleepy. Other drugs which help allergy sufferers are contained in nasal sprays and eye drops also aimed at blocking histamine released locally in the nose and eyes. While these drugs temporarily reduce mild allergic symptoms, they have little effect on more severe reactions such as allergic asthma or anaphylaxis. Severe allergy related breathing difficulties are often treated by inhaling a mist of epinephrine. Persistent allergies are sometimes treated with repeated injections of minuscule amounts of the allergen. This treatment, known as "desensitization therapy", may work by causing production of allergen specific IgG antibodies which interfere in the binding of allergen to mast cell-bound IgE. Preventing this binding also prevents initiation of the allergic cascade which, in turn, means that there won't be an overproduction of IgE.

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