Hypersensitivity reaction

A hypersensitivity reaction is a detrimental immune-mediated response inside the body caused by an overactive immune system. When the body enters a hypersensitive state as a result of an overactive immune system, it is overcompensating in its efforts to fight off foreign substances that invade the body. Although these responses are designed to protect the body from harm, an overreaction of the immune system response can cause the body harm, including tissue injury or physiological dysfunction. Hypersensitivity reactions are divided into two categories: immediate and delayed. Immediate hypersensitivity reactions occur when the body releases antibodies, or proteins that resist disease, to combat foreign substances. Delayed hypersensitive reactions occur when the body releases a type of white blood cell called a T lymphocyte in response to the presence of foreign substances.

Background

The body’s immune system is responsible for recognizing toxins and other foreign substances that are not normal parts of the human body. Once these substances are recognized, the immune system initiates a variety of processes that fight off the invaders so the body does not come to any harm. Foreign substances can enter the body in a number of ways, such as through the mouth, nose, and skin. These substances can also enter the body through cuts and other injuries, and can be prevented by keeping wounds clean and covered.

When substances such as bacteria or viruses enter the body and, in some cases, the bloodstream, they can cause disease. Although the immune system cannot always prevent disease, it can fight disease-causing substances until they are no longer inside the body. For example, when a person contracts the cold or flu virus, they often experience symptoms such as fatigue, sore throat, runny nose, and coughing in response to the virus. The immune system releases proteins and white blood cells that specifically fight this virus and eliminate it from the body, leading to symptom relief and recovery.

The immune system plays a crucial role in fighting disease, but sometimes the immune system’s normal functions react too much, too little, or inappropriately. When the immune system experiences these reactions to a foreign substance, a hypersensitivity reaction can develop. These reactions can cause injury and sometimes death. When antibodies are involved in hypersensitivity reactions, it is called an immediate hypersensitivity reaction. When white blood cells called T lymphocytes are involved in a hypersensitivity reaction, it is called a delayed hypersensitivity reaction.

Overview

Four main types of hypersensitivity reactions exist. Immediate hypersensitivity reactions account for Types I–III, while delayed hypersensitivity reactions account for Type IV. Some professionals feel it is necessary to distinguish certain Type II disorders that bind to cell surface receptors as opposed to the cell surface itself and therefore include a Type V category, but this type of designation is uncommon.

Immediate hypersensitivity reactions are initiated when the immune system releases antibodies to combat a foreign substance, or antigen. The reaction depends upon what type of foreign substance enters the body, how pervasive the substance is, and what type of antibody reacts with the substance. When the body is first exposed to an antigen, it is called the sensitizing dose. The immune system then enters a latent period in which it does not react inside the body. When the same antigen enters the body at a later time, it is called a shocking dose. The shocking dose causes a hypersensitivity reaction and can lead to a number of issues.

Type I reactions involve allergic reactions mediated by the antibody immunoglobulin E (IgE). Immediate hypersensitivity reactions to allergens occur within minutes. Examples of disorders caused by Type I reactions include anaphylaxis, asthma, atopy, and eosinophilic granulomatosis with polyangiitis (formerly Churg-Strauss syndrome).

Type II reactions involve antibody-dependent cell-mediated cytotoxicity (ADCC). Cytotoxicity refers to immune system responses that destroy cells. These reactions are mediated by immunoglobulin M (IgM) and immunoglobulin G (IgG), which are bound to cell surface antigens. In these instances, antigens bind to normal cells that are then targeted for destruction by the immune system. This can lead to a number of harmful consequences, such as the development of autoimmune disease. Examples of disorders related to Type II reactions include autoimmune hemolytic anemia, rheumatic heart disease, Graves’ disease, and Goodpasture syndrome.

Although white blood cells play a role in Type III reactions, IgG is the primary mediator of this type of immediate hypersensitivity reaction. Type III is also referred to as immune-complex reactions because they involve circulating antigen-antibody complexes. An antigen-antibody complex is a molecule formed when an antibody binds to an antigen and is deposited into the blood vessel walls of specific areas of the body. This initiates an inflammatory reaction that can lead to issues such as joint pain and kidney disease. Disorders that commonly occur as a result of a Type III reaction include serum sickness, rheumatoid arthritis, reactive arthritis, hypersensitivity pneumonitis, and systemic lupus erythematosus.

Delayed hypersensitivity reactions, also referred to as Type IV reactions, take a day or more to develop. In delayed hypersensitivity reactions, white blood cells known as T lymphocytes, or T cells, mediate the immune response to antigens. Normally, T cells maintain cellular immunity by releasing substances called lymphokines, which trigger the release of macrophages, or cells that protect against infection. Macrophages ingest harmful foreign substances and remove them from the body. A delayed hypersensitivity reaction occurs as a result of an overreaction of this process that causes the macrophages to act on healthy cells, initiating an inflammatory response that can lead to tissue damage. Examples of disorders caused by Type IV reactions include contact dermatitis, multiple sclerosis, and celiac disease.

Some experts believe this categorization of hypersensitivity reactions is too generalized and does not account for the complex connection between immune system responses and hypersensitivity reactions. An updated classification system was proposed in the late 1990s that separates hypersensitivity reactions into seven categories as follows:

• inactivation/activation antibody reactions
• cytotoxic antibody reactions
• immune-complex reactions
• allergic reactions
• T cell cytotoxic reactions
• delayed hypersensitivity reactions
• granulomatous reactions (inflammation that produces a mass of connective tissue)

Bibliography

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“Hypersensitivity Reactions (Types I, II, III, IV).” New Jersey Medical School, 15 Apr. 2009, njms.rutgers.edu/gsbs/olc/mci/prot/2009/Hypersensitivities09.pdf. Accessed 18 Mar. 2026.

“In Brief: The Innate and Adaptive Immune Systems.” National Library of Medicine, 14 Aug. 2023, www.ncbi.nlm.nih.gov/books/NBK279396/. Accessed 18 Mar. 2026.

Janeway, Charles A., et al., editors. “Hypersensitivity Disease.” Immunobiology: The Immune System in Health and Disease. Garland Science, 2001.

Justiz Vaillant, Angel A., et al. “Immediate Hypersensitivity Reactions.” StatPearls, 29 May 2023, www.ncbi.nlm.nih.gov/books/NBK513315/. Accessed 18 Mar. 2026.

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