Hypersensitivity describes immunologic responses that cause host tissue damage due to exaggerated or inappropriate reactions to an antigen.
Mechanisms and Types
Gell and Coombs classified hypersensitivity reactions into four types based on the underlying immune mechanism and the timing of the response. Type I reactions occur within minutes when IgE antibodies on mast cells bind antigen, leading to the release of histamine and other mediators that cause vasodilation, smooth muscle contraction and increased mucus. These immediate responses include allergic rhinitis, asthma and anaphylaxis. Type II reactions are mediated by IgG or IgM antibodies directed against antigens on cells or extracellular matrix. Binding activates complement or recruits phagocytes, resulting in cell lysis or dysfunction; examples include hemolytic anemia and transfusion reactions. Type III hypersensitivity involves the formation of immune complexes that deposit in tissues and activate complement, leading to inflammation and tissue injury as seen in serum sickness or some forms of glomerulonephritis. Type IV, or delayed type hypersensitivity, is mediated by T lymphocytes. After sensitization, re-exposure to antigen causes T cell activation and cytokine release, attracting macrophages and causing tissue damage; contact dermatitis and the tuberculin skin test are examples. While the classification aids understanding, reactions can involve overlapping mechanisms.
Clinical Manifestations and Examples
Allergic conditions such as hay fever and food allergies represent type I hypersensitivity and show how innocuous antigens can trigger severe symptoms when IgE-sensitized mast cells degranulate. In type II reactions, antibodies can target red blood cells after a mismatched transfusion, causing hemolysis. Some drugs can bind to cell surfaces and create new antigenic determinants that elicit antibody responses, leading to thrombocytopenia. Immune complex deposition in joints and blood vessels produces the arthritis and rash of serum sickness. Autoimmune diseases such as systemic lupus erythematosus are driven in part by type III mechanisms when antibodies form complexes with self-antigen. Type IV reactions manifest hours to days after exposure; sensitization to nickel or poison ivy results in a localized skin rash through T cell mediated inflammation. The tuberculin skin test uses a delayed reaction to purified protein derivative to detect past exposure to Mycobacterium tuberculosis.
Hypersensitivity reflects the double-edged nature of immunity; mechanisms designed to protect can instead harm when regulation fails. Understanding the distinct pathways helps clinicians predict timing, manage symptoms and select appropriate therapies. Many common allergic and autoimmune conditions fall under these categories, illustrating the clinical relevance of hypersensitivity.
Related Terms: Allergy, Autoimmune disease, Anaphylaxis, Immunoglobulin E, Immune complex