When a presensitized individual is exposed to an allergen, it can lead to a rapid immune response that occurs almost immediately. Such a response is called an allergy and is classified as a type I hypersensitivity. Allergens may be seemingly harmless substances such as animal dander, molds, or pollen. Allergens may also be substances considered innately more hazardous, such as insect venom or therapeutic drugs. Food intolerances can also yield allergic reactions as individuals become sensitized to foods such as peanuts or shellfish. Regardless of the allergen, the first exposure activates a primary IgE antibody response that sensitizes an individual to type I hypersensitivity reaction upon subsequent exposure.
For susceptible individuals, a first exposure to an allergen activates a strong TH2 cell response (Figure 19.3). Cytokines interleukin (IL)-4 and IL-13 from the TH2 cells activate B cells specific to the same allergen, resulting in clonal proliferation, differentiation into plasma cells, and antibody-class switch from production of IgM to production of IgE. The fragment crystallizable (Fc) regions of the IgE antibodies bind to specific receptors on the surface of mast cells throughout the body. It is estimated that each mast cell can bind up to 500,000 IgE molecules, with each IgE molecule having two allergen-specific fragment antigen-binding (Fab) sites available for binding allergen on subsequent exposures. By the time this occurs, the allergen is often no longer present and there is no allergic reaction, but the mast cells are primed for a subsequent exposure and the individual is sensitized to the allergen.
On subsequent exposure, allergens bind to multiple IgE molecules on mast cells, cross-linking the IgE molecules. Within minutes, this cross-linking of IgE activates the mast cells and triggers degranulation, a reaction in which the contents of the granules in the mast cell are released into the extracellular environment. Preformed components that are released from granules include histamine, serotonin, and bradykinin. The activated mast cells also release newly formed lipid mediators (leukotrienes and prostaglandins from membrane arachadonic acid metabolism) and cytokines such as tumor necrosis factor.
The chemical mediators released by mast cells collectively cause the inflammation and signs and symptoms associated with type I hypersensitivity reactions. Histamine stimulates mucus secretion in nasal passages and tear formation from lacrimal glands, promoting the runny nose and watery eyes of allergies. Interaction of histamine with nerve endings causes itching and sneezing. The vasodilation caused by several of the mediators can result in hives, headaches, angioedema (swelling that often affects the lips, throat, and tongue), and hypotension (low blood pressure). Bronchiole constriction caused by some of the chemical mediators leads to wheezing, dyspnea (difficulty breathing), coughing, and, in more severe cases, cyanosis (bluish color to the skin or mucous membranes). Vomiting can result from stimulation of the vomiting center in the cerebellum by histamine and serotonin. Histamine can also cause relaxation of intestinal smooth muscles and diarrhea.
Type I hypersensitivity reactions can be either localized or systemic. Localized type I hypersensitivity reactions include hay fever rhinitis, hives, and asthma. Systemic type I hypersensitivity reactions are referred to as anaphylaxis or anaphylactic shock. Although anaphylaxis shares many symptoms common with the localized type I hypersensitivity reactions, the swelling of the tongue and trachea, blockage of airways, dangerous drop in blood pressure, and development of shock can make anaphylaxis especially severe and life-threatening. In fact, death can occur within minutes of onset of signs and symptoms.
Late-phase reactions in type I hypersensitivities may develop 4–12 hours after the early phase and are mediated by eosinophils, neutrophils, and lymphocytes that have been recruited by chemotactic factors released from mast cells. Activation of these recruited cells leads to the release of more chemical mediators that cause tissue damage and late-phase symptoms of swelling and redness of the skin, coughing, wheezing, and nasal discharge.
Individuals who possess genes for maladaptive traits, such as intense type I hypersensitivity reactions to otherwise harmless components of the environment, would be expected to suffer reduced reproductive success. With this kind of evolutionary selective pressure, such traits would not be expected to persist in a population. This suggests that type I hypersensitivities may have an adaptive function. There is evidence that the IgE produced during type I hypersensitivity reactions is actually meant to counter helminth infections. Helminths are one of few organisms that possess proteins that are targeted by IgE. In addition, there is evidence that helminth infections at a young age reduce the likelihood of type I hypersensitivities to innocuous substances later in life. Thus it may be that allergies are an unfortunate consequence of strong selection in the mammalian lineage or earlier for a defense against parasitic worms.
Parker, N., Schneegurt, M., Thi Tu, A.-H., Forster, B. M., & Lister, P. (n.d.). Microbiology. Houston, Texas: OpenStax. Access for free at: https://openstax.org/details/books/microbiology