Type I Hypersensitivity Reaction

The immune system plays a vital role in defending the body against pathogens; however, it can also produce exaggerated responses known as hypersensitivity reactions. The Gell and Coombs classification system categorizes these reactions into 4 types. Type I hypersensitivity, also known as immediate hypersensitivity, is an immunoglobulin E (IgE)-mediated immune response that occurs when the immune system overreacts to typically harmless environmental antigens. Upon reexposure to the allergen, previously sensitized mast cells and basophils rapidly degranulate, releasing histamine, leukotrienes, prostaglandins, and other inflammatory mediators. This cascade produces a wide range of clinical manifestations, including urticaria, allergic rhinitis, asthma, food allergies, atopic dermatitis, and angioedema. In severe cases, this reaction can progress to anaphylaxis—a potentially life-threatening emergency requiring immediate intervention. Types II, III, and IV hypersensitivity reactions represent distinct immune-mediated mechanisms that can also lead to tissue damage and clinical disease. The following is a brief description of these hypersensitivity reactions based on the Gell and Coombs classification: Type II hypersensitivity reaction: Type II hypersensitivity is an antibody-mediated reaction against cells or tissues of the body in which IgG or IgM antibodies bind to antigens on the surface of cells or tissues, leading to destruction through complement activation or antibody-dependent cell-mediated cytotoxicity. Examples include autoimmune hemolytic anemia, hemolytic disease of the newborn, and Goodpasture syndrome. : Type III hypersensitivity reaction: This reaction involves the formation of circulating antigen-antibody complexes that deposit in tissues, such as the skin, joints, or kidneys, triggering complement activation and inflammation. Tissue damage occurs through the recruitment of neutrophils and the release of inflammatory mediators. Examples of type III hypersensitivity reactions include serum sickness, systemic lupus erythematosus, and poststreptococcal glomerulonephritis. : Type IV hypersensitivity reaction: Type IV hypersensitivity is a T-cell–mediated reaction with a delayed onset, typically appearing 48 to 72 hours after exposure to an allergen. Unlike the other hypersensitivity types, this reaction does not involve antibodies. Instead, antigen-presenting cells activate sensitized T lymphocytes, which release cytokines that recruit and activate macrophages and cytotoxic T cells. Examples include contact dermatitis, such as that caused by poison ivy; tuberculin skin testing; and granulomatous diseases, including sarcoidosis and tuberculosis. Each type reflects a unique pathway of immune dysregulation, helping guide diagnosis and targeted therapy. Please see StatPearls' companion resources, "Type II Hypersensitivity Reaction," "Type III Hypersensitivity Reaction," and "Type IV Hypersensitivity Reaction," for further information. A newer classification by Sell and colleagues expands the system to 7 categories; however, this activity focuses on the classic type I hypersensitivity reaction. Type I hypersensitivity reactions typically occur within minutes of allergen exposure but can also manifest as late-phase responses or chronic allergic inflammation. The sensitization phase begins when antigen-presenting cells activate T helper (Th) cells, which in turn stimulate B cells to produce allergen-specific IgE. These IgE antibodies bind to high-affinity FcεRI receptors on mast cells and basophils. Upon reexposure, the allergen cross-links bound IgE, triggering degranulation and the release of inflammatory mediators. Clinical symptoms vary depending on the site of exposure. Risk factors for type I hypersensitivity include genetic predisposition, environmental triggers, geographic differences, and the hygiene hypothesis. This hypothesis proposes that reduced early exposure to microbes may increase susceptibility to allergies. Management is guided by symptom severity and primarily involves allergen avoidance, supplemented with the use of antihistamines, corticosteroids, bronchodilators, epinephrine, or allergen immunotherapy when appropriate. Prognosis varies from full resolution to the need for long-term treatment, highlighting the importance of prompt recognition and coordinated care to improve outcomes.