Causes of Allergies

This information was reviewed and approved by Carah Santos, MD (12/5/2022).

Allergies and allergic reactions occur when the immune system misidentifies harmless foreign substances, called allergens, and reacts to them as if they are harmful. Specifically, allergy symptoms result when the immune system makes IgE antibodies that bind to a specific allergen in an effort to protect us from otherwise harmless allergens. Allergens can include things like pollen, animal dander, medications, and foods.

IGE is a protein that can be made by patients who have allergies and asthma. It often is not made by patients who do not have any allergic symptoms.

It is often found in the blood as well as tissues such as the skin in patients who have atopic dermatitis or the lung. In patients with asthma, the nose in patients with hay fever and the gut in patients with food allergy. Once it's made in the body, it goes into the bloodstream and then gets deposited in the tissue where when the tissue encounters, what the patient is allergic to. It triggers allergic reactions because IGE binds to the cells in that tissue that recognize the allergen to which the patient is allergic to.

By discovering IGE, we actually were able to determine at several levels new therapies for allergic disease. First of all, the immunology community has been able study why people with allergic diseases actually make IGE and that has led to multiple pathways and targets along the way that actually modulate or regulate how IGE is being produced. And one can actually target each of these molecules to control how much IGE somebody is making. Another example of being able to advance therapy is that by being able to measure what the IGE is directed to, we can actually tell a patient what they should be avoiding and also to do much more improved forms of immunotherapy to specific allergens.

Finally, we also have been able to partner with pharmaceutical companies to make monoclonal antibodies which actually can neutralize IGE and have actually been introduced for treatment of severe allergic asthma as well as anaphylaxis to food allergens such as peanut.

How People Develop Allergies

To become allergic, a person must have a genetic predisposition for allergy, meaning a personal or family history of allergies. Then they must be exposed to a sensitizing allergen. Most allergies begin in early childhood, and early environmental factors play a major role in the development of allergies.

Primary Exposure - Sensitization

An allergen, such as mold spores or pollen, enters the body through the mouth or nose or lands on the skin. In a person with allergies, white blood cells (T cells) identify the allergen as foreign and release chemicals in response. These chemicals travel through the blood and instruct another kind of white blood cell (B cells) to produce IgE antibodies. Some of these IgE antibodies attach to the outside of another special type of white blood cell called a mast cell. Mast cells are scattered throughout the skin and respiratory tract. Their purpose is to help mediate the inflammatory response of the immune system. IgE antibodies can remain attached to mast cells for many years.

Secondary Exposure - The Cause of Allergy Symptoms

When the same allergen is encountered again, it binds directly to the IgE antibody attached to the outside of mast cells. This causes the mast cells to become activated and release chemicals, such as histamine. Histamine is an example of a chemical mediator — a special "messenger" chemical that immune cells use to talk to each other.

Histamine is one of the best-known mediators. It is responsible for causing many of the symptoms associated with allergies. Histamine opens small blood vessels, causing them to leak fluid. This results in inflammation: warming and swelling of the skin, itching and watery eyes. Histamine causes sneezing and the increased mucus production in the nasal cavity and airways that leads to runny nose, postnasal drip and cough.

Why Allergy Is Selective

Some people are allergic to lots of things. What a person is allergic to is determined by many factors, including the environment, the history of exposures, the person's genes and the way the immune system works.

The skin, the respiratory tract and the digestive tract are the organs that interact with the external environment. They are also the sites most affected by allergic disorders. The immune system protects the person against foreign substances and microorganisms. Harmful "non-self" things are eliminated, while beneficial "self" things are allowed to remain in place. A person does not need to respond to most of the environmental substances to which he/she is exposed. Allergic diseases are caused by the immune system generating needless inflammatory responses to substances that are otherwise harmless.

An antigen is a substance that generates an immune response. If this response is allergic, the antigen may also be called an allergen . Each allergen has a unique molecular structure. The immune system uses the "blueprint" of this structure to make special proteins called antibodies that fit their corresponding allergens very specifically in a lock-and-key fashion. The antibodies that participate in the allergic response belong to the IgE class. Each IgE antibody is restricted to one allergen, but an individual may have many distinct antibodies that account for multiple allergic susceptibilities.

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