26.13 Allergies are an inappropriate immune response to a harmless substance.

A three-year-old girl bites into a peanut butter sandwich. She immediately develops hives around her mouth and begins vomiting. She is having an allergic reaction. This is only the second time she’s eaten peanut butter. Unfortunately, her story is not unusual. The CDC estimates that approximately 3 million children in the United States have food allergies, 90% caused by just eight foods: peanuts, tree nuts, milk, eggs, fish, shellfish, soy, and wheat. Allergies are the result of an inappropriate immune response to what should be a harmless substance.

In discussing antibodies earlier in the chapter, we did not focus on the groups of antibodies that differ in their constant (heavy) region at the base of the “Y.” There are five classes of antibodies, differing in their chemical structure in this region. When antibodies of one of these classes bind to mast cells (the white blood cells found in tissues), they cause the mast cells to release histamine and cytokines, both of which cause local blood vessels to become dilated and leaky (as we’ve seen, standard parts of the inflammatory response), and recruit other immune cells to the site.

This mast cell-binding class of antibodies can cause much harm to the body if they are made in response to an allergen, an antigen that causes an allergic response. On first encounter, an allergen induces a normal humoral response: memory cells form, and plasma cells secrete antibodies specific to the allergen. The antibodies bind to the surface of mast cells and can remain bound for months and maybe even years. The mast cells are now “sensitized” to the allergen. In a second exposure, the allergen binds to the antibodies that are still attached to the mast cells—which are now “activated.” This time, allergen binding causes the mast cells to release histamine, which causes the blood vessels to dilate and become leaky, and inflammation ensues (FIGURE 26-33).

The effect of different allergens reflects which particular mast cells have been exposed to the allergen and thus activated. Most allergic reactions occur in the digestive or respiratory tracts, because this is where the body first encounters an eaten or inhaled allergen. Allergic reactions associated with food often lead to vomiting or diarrhea, but can also lead to hives and other symptoms if the allergen enters the bloodstream. Respiratory allergens, such as pollen and dust, can cause a runny nose and teary eyes (“hay fever”) in the upper respiratory tract, or can result in asthma, a chronic inflammatory disease of the lower respiratory tract that causes wheezing, coughing, and shortness of breath.

Taking an antihistamine can alleviate some allergies, as these medicines block the inflammatory effects of histamine. Other medicines block mast cells from releasing histamine. Steroids are prescribed for more severe allergies. Steroids block the production of the chemicals released from immune cells, thus preventing the migration of more inflammatory cells, such as macrophages and neutrophils, to the site of inflammation. Additionally, steroids can block the killing ability of these phagocytes, resulting in less damage to the inflamed tissue.

An individual with a severe allergic response may experience anaphylactic shock, a life-threatening allergic reaction that is systemic, meaning that it is not localized to the site of exposure. Anaphylactic shock can lead to severe respiratory distress, as the throat swells and asthma develops. Swelling in various tissues means there is less fluid in the blood system, and this can lead to dangerously low blood pressure. Individuals with severe allergies often carry with them a dose of adrenaline, also called epinephrine, a chemical found naturally in our bodies (see Section 24-5) and also manufactured by several drug companies. Epinephrine, which can be injected if needed, reverses the effects of histamine on blood vessels, but it must be injected quickly, because death can occur rapidly from anaphylactic shock.

A common method of testing for allergies is called skin allergy testing, in which microscopic amounts of one or more potential allergens are injected under the skin—usually on the back or the forearm. The development of a rash can indicate a hypersensitivity to that allergen, enabling the person to take steps to reduce exposure to the allergen (FIGURE 26-34).