To produce an allergic reaction against a given antigen, an individual must first be exposed to the antigen under conditions that result in the production of IgE antibodies. Allergic symptoms occur when an individual who has been sensitized in this fashion has subsequent exposure to the antigen. Exposure can lead to different clusters of symptoms, characterized by the tissues that are most prominently affected. The most common forms of allergic response in developed countries are to airborne allergens, causing symptoms that affect predominantly the nasal passages (allergic rhinitis), the eyes (allergic conjunctivitis), or the lower airways and lungs (asthma). Ingested allergens can lead to food allergy, sometimes affecting only the gastrointestinal tract (for example, eosinophilic esophagitis), but not infrequently involving locations distant from the site of antigen entry. Reactions that occur at locations distant from the site of entry of the challenging antigen are considered to be systemic reactions, and are thought to occur because of spread of the antigen throughout the body via the blood circulation. Systemic reactions can be limited to a single distant organ, causing hives (also called urticaria) when they target the skin, wheezing (or bronchospasms) when they involve the lungs, and life-threatening lowering of the blood pressure when they target the vascular system. Serious systemic reactions are designated by the term anaphylaxis. It is not known why sensitization with a particular allergen in one individual leads to local reactions at the time of allergen challenge, whereas sensitization with the same allergen can yield anaphylaxis in another individual. In fact, even in a single individual, a challenge that usually yields only a mild local reaction can be followed at the time of another challenge by a severe systemic reaction.
Atopic individuals often develop sensitization to many different antigens, and can express multiple forms of allergic symptoms, which depend on the route and quantity of allergen—for example, atopic eczema that develops in childhood in response to sensitization to food antigens is followed in a sizable proportion of those individuals developing allergic rhinitis and/or asthma in response to airborne allergens. This progression of allergic responses in some individuals from atopic eczema in childhood to allergic rhinitis and eventually to asthma in later life has been termed the atopic march. Allergic reactions in non-atopic people, in contrast, are predominantly due to sensitization to one specific allergen, such as bee venom or a drug such as penicillin, and can develop at any time of life. It is important to remember, however, that not all encounters with a potential allergen will lead to sensitization, and not all sensitizations will lead to a symptomatic allergic response, even in atopic individuals.
The immune response leading to IgE production in response to antigen is driven by two main groups of signals that together are typical of type 2 immune reactions. The first consists of signals that favor the differentiation of naive T cells to a TH2 phenotype. The second comprises TH2 cytokines and co-stimulatory signals that stimulate B cells to switch to the production of IgE. As described in Section 9-21, the fate of a naive CD4 T cell responding to an antigenic peptide presented by a dendritic cell is determined by the cytokines it is exposed to before and during this response, and by the intrinsic properties of the antigen, the antigen dose, and the route of presentation. Exposure to IL-4, IL-5, IL-9, and IL-13 favors the development of TH2 cells, whereas exposure to IFN-γ and IL-12 (and its relative IL-27) favors TH1-cell development.