Hypersensitivity
An immune response causing tissue damage, reproducible upon re-exposure to antigen.
Hypersensitivity, or a hypersensitivity reaction, describes an immune response that, through its own mechanisms, leads to notable tissue damage or disrupted physiological function. This reaction can be triggered by pathogens, harmless environmental substances, or the body’s own antigens, and it consistently reappears when the antigen is encountered again. Although these mechanisms can sometimes be protective—for instance, in fighting off infections—they are defined by the collateral harm they cause, which often outweighs any benefit. These reactions are very widespread: hay fever occurs in roughly 1 in 10 people globally, asthma impacts hundreds of millions, and about 1 in 12 individuals has an autoimmune condition.
In 1963, Philip George Houthem Gell and Robin Coombs created a structured way to categorize hypersensitivities, based on the antigen types and immune responses involved.
- Type I: an immediate reaction mediated by Immunoglobulin E (IgE). - Type II: an antibody-driven reaction, typically involving IgG, IgM, or both. - Type III: a reaction mediated by immune complexes, involving IgG, the complement system, and phagocytes. - Type IV: a delayed reaction mediated by T cells.
Each type also differs in how quickly symptoms appear after exposure. Type I, called immediate hypersensitivity, shows up within seconds to minutes. Types II (cytotoxic) and III (immune complex) develop within hours. Type IV, or delayed-type hypersensitivity (DTH), emerges days later.
It is important to note that the Gell-Coombs classification does not align with the modern system of categorizing immune responses as type 1, type 2, or type 3. For example, type I hypersensitivities are inappropriate versions of type 2 immune responses (driven by IgE, IL-4, and IL-13). Type IV reactions, in the original Gell-Coombs framework, correspond to type 1 immune responses (driven by IFN-γ, Th1 cells, and CD8 T cells). Types II and III can involve a mix of different immune response types.
Autoimmune diseases often manifest as type II, III, or IV hypersensitivity reactions as their core pathological process. A single disease can involve multiple hypersensitivity types at once, and the dominant type can shift over time.
Quick Facts
- Field
- Immunology
Facts from the source article.
Lore & Background
In 1963, Philip George Houthem Gell and Robin Coombs introduced a systematic classification of the different types of hypersensitivity based on the types of antigens and immune responses involved. According to this system, known as the Gell and Coombs classification, there are four types: Type I, an Immunoglobulin E (IgE)-mediated immediate reaction; Type II, an antibody-mediated reaction canonically involving IgG, IgM, or both; Type III, an immune complex-mediated reaction involving IgG, complement system and phagocytes; and Type IV, a T cell-mediated, delayed hypersensitivity reaction. Each type differs in the time to symptoms following exposure: Type I occurs within seconds to minutes, Types II and III within hours, and Type IV occurs days after exposure.
The Gell-Coombs classification does not correspond to the modern classification of immune responses as type 1, type 2, or type 3. For example, Type I hypersensitivities are inappropriate manifestations of type 2 immune responses, while Type IV are type 1 immune responses. Autoimmune diseases manifest as some form of type II, III, or IV hypersensitivity reaction as their key pathological process. It is possible to have multiple types of hypersensitivity reaction contribute to a disease at the same time, and the type central to a given disease can change over time or by region. Thus, these categories are best viewed as guides rather than absolute rules.
Reader's Guide
An understanding of hypersensitivity reactions is important in guiding diagnostic and treatment decisions for the conditions that are mediated by them. The term 'allergy' has undergone significant revision: originally referring specifically to type I hypersensitivities, modern professional societies define allergy as any immunologic mechanism that produces a hypersensitivity reaction. This means anything under the Gell and Coombs classification can be considered an allergy, so long as the antigen originates from outside the body. However, many still use 'allergy' specifically for type I hypersensitivity, so clarification is advisable. The term 'allergen' has not been updated and specifically refers to any antigen bound by IgE. Over time, additional types of hypersensitivity reactions have been defined beyond the four proposed by Gell and Coombs, including types V, VI, and VII under the EAACI 2023 position paper classification, which represent non-allergic hypersensitivity reactions. Another classification, proposed by Pichler mainly for drug hypersensitivities, subdivides type IV and adds non-allergic hypersensitivity and pharmacological interaction with immune receptor. These classification schemes are constantly being revised and updated across geographies and specialties.
Did You Know?
- Type I hypersensitivity occurs within seconds to minutes of exposure, while Type IV occurs days after exposure.
- The Gell and Coombs classification was introduced in 1963 by Philip George Houthem Gell and Robin Coombs.
- The term 'allergen' specifically refers to any antigen bound by IgE, and has not been updated to reflect modern definitions of allergy.
Frequently Asked Questions
What is Hypersensitivity?
Hypersensitivity refers to an overreactive immune response that ends up damaging the body's own tissues or disrupting normal physiological processes. It is triggered when the immune system encounters a specific antigen—whether a pathogen, an environmental irritant, or even the body's own proteins—and the reaction reliably repeats each time that same trigger is met again.
Who developed the Hypersensitivity classification system?
The now-standard framework dividing hypersensitivity into distinct types was introduced in 1963 by immunologists Philip George Houthem Gell and Robin Coombs. Their work established the four-type model that remains the backbone of how these reactions are categorized in medicine.
How many types of Hypersensitivity are there?
Under the Gell and Coombs framework, hypersensitivity is divided into four distinct types. Each type involves a different mechanism by which the immune system's response causes collateral tissue injury.
How widespread are Hypersensitivity reactions in the real world?
These reactions are extraordinarily common: roughly one in ten people globally suffers from hay fever, hundreds of millions live with asthma, and about one in twelve individuals deals with some form of autoimmune disease. Together, these figures show that hypersensitivity is one of the most prevalent categories of immune-mediated harm.
Why is Hypersensitivity considered a problem if the immune system is just doing its job?
While the underlying immune mechanisms can serve a protective role—such as helping the body clear an infection—the defining feature of hypersensitivity is that the collateral tissue damage or functional disruption caused by the response outweighs any protective benefit. In other words, the 'protection' inflicts more harm than the original threat would have.
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