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What Causes an Allergic Response?

The immune system normally functions to protect the body against viruses, bacteria, fungi, and other pathogens by targeting these substances for destruction upon recognition. However, an allergic response arises when your immune system mistakes harmless substances as potential pathogens and attacks them.

Th1 and Th2 Immune Responses in Allergies

T lymphocytes are immune cells that recognize foreign pathogens and also produce cell-signaling cytokine proteins, which facilitate immunological communication. The two main subsets of T cells—Th1 and Th2—complement one another to produce a comprehensive immune response against invading pathogens.

Th1 cytokines trigger the destruction of pathogens that enter the cells (such as viruses). They are also responsible for cell-mediated immune response and can perpetuate autoimmune reactions. Th2 cytokines destroy extracellular pathogens that invade the blood and other body fluids. As will be later described, an imbalance within the Th1-Th2 paradigm favoring Th2 underlies the increased susceptibility to allergies, called atopy, that some individuals experience.11

A Closer Look at the Immunology of an Allergic Response

According to the Th2 hypothesis of allergy, atopy results from an overproduction of Th2 cytokines in response to allergens. The atopic individual is genetically predisposed such that he is more likely to over-produce Th2 cytokines and muster an insufficient Th1 response; the result of this imbalance is production of antibodies against normally innocuous environmental substances.12

The first time an allergen is encountered, the Th2 cytokines interleukin-4 (IL-4) and/or IL-13 alert B cells (components of the immune system responsible for antibody generation) to produce a particular type of antibody called immunoglobulin E (IgE); this process is called "sensitization."

Next, circulating IgE alerts other immune cells (basophils in the blood and mast cells in the skin and mucosal lining) that they should be ready to destroy the antigen in question if they detect it. IgE also triggers the formation of "memory" T cells, which are able to react much more quickly to future recognition of the same antigen.
Upon subsequent exposure to the same antigen, an atopic individual will have a dual response characterized by an immediate, or acute reaction within minutes, and a delayed, or late-phase reaction within the next 4‒8 hours after exposure.13

Acute response. During an acute immune reaction, IgE antibodies, upon binding (crosslinking) a previously categorized antigen, provoke release of allergic mediators including histamine, prostaglandins, and leukotrienes from mast cells and basophils; these chemicals are responsible for the classic symptoms we think of in association with "allergy" (eg, itchy skin, runny nose, etc.).

This immediate IgE reaction responds to antihistamines and decongestants.12

Late-phase response. After the acute response subsides, late-phase reactions can occur and produce long-term effects. The late-phase reaction manifests when an antigen is presented to a T cell (especially those already "primed" by IgE specific to that antigen) that then releases cytokines (primarily IL-5), which induce degranulation (release of allergic mediators) from another type of immune cell called an eosinophil.

For example, the pathogenesis of allergic rhinitis, atopic dermatitis and asthma, are thought to be influenced more by the late-phase immune reactions. In general, late-phase allergic reactions respond to anti-inflammatory agents such as corticosteroids.

Together, allergic mediators including histamine, leukotrienes and interleukins cause a typical "allergy attack." In the skin, they cause itchy hives, rashes and swelling. In the nasal cavities, these chemicals cause runny nose, tearing, burning or itching eyes, itching in the nose, throat, roof of the mouth and eyes. The release of histamine and other mediators in the lungs cause muscles of the bronchial wall to tighten, become inflamed and produce excessive mucus. This causes the symptoms of asthma—wheezing, difficulty breathing and coughing. In the digestive system, histamine can cause vomiting, diarrhea and stomach cramps.