Allergy is an overactive immune (hypersensitivity) reaction to a harmless entity sensed as dangerous by the immune system. Type 1 hypersensitivity involves the production of Ig-E antibodies against an allergen. Different types of allergies have been described and include food allergies, drug allergies, allergies to plant components (pollen) and allergies to animal products. Manifestations of allergic reactions include redness of the skin (contact allergy), sneezing, wheezing and edema and can ultimately lead to anaphylactic shock. Different populations of immune cells are engaged in an allergic reaction, including antigen presenting cells (e.g., dendritic cells), mast cells and Ig-E producing B cells and T cells.

Food allergy and oral tolerance

Food allergies can be subdivided into three main categories based on the extent of involvement of Ig-E.¹

Ig-E-mediated food allergy

Ig-E-mediated food allergy involves the binding of food allergens to Ig-E molecules leading to the activation of effector cells releasing histamine (immediate response) followed by allergic inflammation with increased leukotrienes, platelet activating factor (PAF), and IL-4, IL-5 and IL-13 cytokines.¹

Non-Ig-E mediated food allergy

Non-Ig-E mediated food allergies mostly affect the gastrointestinal tract. In food protein–induced ailments such as food protein–induced enterocolitis syndrome (FPIES), food protein–induced proctocolitis (FPIP) and food protein enteropathy (FPE), allergen-specific T cells have been described.¹ Cutaneous exposure to food allergens has been shown to promote sensitization and TH2 mediated responses in the gut. Retinoic acid secreted by antigen presenting cells can induce the expression of gut homing receptors in T cells but also Ig-A secreting B cells and provoke their migration to the gut.^1,2 Exposure to dietary gluten causes celiac disease, a T-cell-mediated autoimmune disorder in individuals predisposed to autoimmune diseases.³

Mixed food allergy

Mixed food allergy involves Ig-E dependent and Ig-E independent pathways. Some examples include atomic dermatitis and eosinophilic gastrointestinal disorders (e.g., eosinophilic esophagitis). In this type of reaction, a distinct Th-2 response profile (eotaxin‐3, IL‐5, IL‐5 receptor α‐chain and IL‐13) along with tissue infiltration by inflammatory eosinophils and elevated levels of IL‐1α, IL‐6 and IL‐8 in the peripheral blood are observed.^1,4

Drug allergy

Adverse drug reactions (ADR) are divided into two types: type A and type B. Type A ADR is a predictable reaction related to the dosing of a drug. Type B ADR is unpredictable and not related to the drug dose and the response closely resemble an allergic reaction.⁵ Antibiotics allergy and vaccine hypersensitivity are two examples of drug allergies. These reactions can be Ig-E or non-Ig-E mediated. 

Antibiotics allergy

In some antibiotic allergies (e.g., angioedema, urticarial) Ig-E mediated reactions are induced after binding of antibiotics allergens to Ig-E expressed on mast cells and basophils. In other allergies such as those induced by vancomycin and fluoroquinolones, mast-cell and basophils are activated and non-IgE-mediated reactions are elicited but no immunological memory is formed.^6,7

Vaccine hypersensitivity

Vaccine-associated hypersensitivity reactions can occur because of a reaction with a vaccine component (e.g., antigen of interest) or with a preservative or other microbial antigen (e.g., tetanus) used to potentiate vaccine-induced immune responses (e.g., aluminum adjuvant). Several types of hypersensitivity reactions have been described, including Ig-E, Ig-G, complement mediated responses as well as delayed T cell–mediated responses and rare cases of anaphylaxis (1.31 cases per million doses).⁸