Hypersensitivity (also called hypersensitivity reaction or intolerance) refers to undesirable reactions produced by the normal immune system, including allergies and autoimmunity. They are usually referred to as an over-reaction of the immune system and these reactions may be damaging and uncomfortable. This is an immunologic term and is not to be confused with the psychiatric term of being hypersensitive which implies to an individual who may be overly sensitive to physical (ie sound, touch, light, etc.) and/or emotional stimuli. Although there is a relation between the two – studies have shown that those individuals that have ADHD (a psychiatric disorder) are more likely to have hypersensitivity reactions such as allergies, asthma, eczema than those who do not have ADHD.[1]

Types of hypersensitivity reactions
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Medical condition
Specialty Immunology

Hypersensitivity reactions can be classified into four types.

Type I: IgE mediated immediate reaction

Type II: Antibody-mediated cytotoxic reaction (IgG or IgM antibodies)

Type III: Immune complex-mediated reaction

Type IV: Cell-mediated, delayed hypersensitivity reaction[2]

The first three types are considered immediate hypersensitivity reactions because they occur within 24 hours. The fourth type is considered a delayed hypersensitivity reaction because it usually occurs more than 12 hours after exposure to the allergen, with a maximal reaction time between 48 and 72 hours.[3]

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The Gell and Coombs classification of hypersensitivity is the most widely used, and distinguishes four types of immune response which result in bystander tissue damage.[4]

Immunologic aspects of hypersensitivity reactions
Type Alternative names Antibodies or Cell Mediators Immunologic Reaction Examples
I Fast response which occurs in minutes, rather than multiple hours or days. Free antigens cross link the IgE on mast cells and basophils which causes a release of vasoactive biomolecules. Testing can be done via skin test for specific IgE.[5]
II Antibody (IgM or IgG) binds to antigen on a target cell, which is actually a host cell that is perceived by the immune system as foreign, leading to cellular destruction via the MAC. Testing includes both the direct and indirect Coombs test.[6]
III Antibody (IgG) binds to soluble antigen, forming a circulating immune complex. This is often deposited in the vessel walls of the joints and kidney, initiating a local inflammatory reaction.[7]
IV Cells

T helper cells (specifically Th1 cells) are activated by an antigen presenting cell. When the antigen is presented again in the future, the memory Th1 cells will activate macrophages and cause an inflammatory response. This ultimately can lead to tissue damage.[8]

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