Hypersensitivity

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This editable Main Article is under development and subject to a disclaimer.

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## Contents

* 1 Classification
* 1.1 Type 1 - immediate (or atopic, or anaphylactic)
* 1.2 Type 2 - antibody-dependent
* 1.3 Type 3 - immune complex diseases
* 1.4 Type 4 - cell-mediated (delayed-type hypersensitivity, DTH)
* 1.5 Type 5 - stimulatory
* 2 References

In medicine, hypersensitivity is an immune system disease that is defined as "altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen.."[1]

## Classification[edit]

The four-group Gell and Coombs classification of immune reactions was proposed in 1963.[2]

### Type 1 - immediate (or atopic, or anaphylactic)[edit]

For more information, see: Immediate hypersensitivity.

Type 1 hypersensitivity is defined as "hypersensitivity reactions which occur within minutes of exposure to challenging antigen due to the release of histamine which follows the antigen-antibody reaction and causes smooth muscle contraction and increased vascular permeability."[3]

Examples include allergic asthma, allergic conjunctivitis, allergic rhinitis ("hay fever"), anaphylaxis, angioedema, eosinophilia, and urticaria (hives).

### Type 2 - antibody-dependent[edit]

In type 2 hypersensitivity, the antibodies produced by the immune response bind to antigens on the patient's own cell surfaces. The antigens recognized in this way may either be intrinsic ("self" antigen, innately part of the patient's cells) or extrinsic (absorbed onto the cells during exposure to some foreign antigen, possibly as part of infection with a pathogen). These cells are recognised by macrophages or dendritic cells which act as antigen presenting cells, this causes a B cell response where antibodies are produced against the foreign antigen.

An example here is the reaction to penicillin where the drug can bind to red blood cells causing them to be recognised as different, B cell proliferation will take place and antibodies to the drug are produced. IgG and IgM antibodies bind to these antigens to form complexes that activate the classical pathway of complement activation for eliminating cells presenting foreign antigens (which are usually, but not in this case, pathogens). That is, mediators of acute inflammation are generated at the site and membrane attack complexes cause cell lysis and death. The reaction takes hours to a day.

Another form of type 2 hypersensitivity is called antibody-dependent cell-mediated cytotoxicity (ADCC). Here, cells exhibiting the foreign antigen are tagged with antibodies (IgG or IgM). These tagged cells are then recognised by natural killer (NK) cells and macrophages (recognised via IgG bound (via the Fc region) to the effector cell surface receptor, CD16 (FcγRIII)), which in turn kill these tagged cells.

Some examples:

* Autoimmune hemolytic anemia
* Goodpasture's syndrome
* Pemphigus
* Pernicious anemia (if autoimmune)
* Immune thrombocytopenia
* Transfusion reactions
* Hashimoto's thyroiditis
* Graves disease (see type V below)
* Myasthenia gravis (see type V below)
* Rheumatic fever
* Hemolytic disease of the newborn (erythroblastosis fetalis)
* Acute transplant rejection

### Type 3 - immune complex diseases[edit]

Type 3 hypersensitivity occurs when antigens and antibodies are present in roughly equal amounts, causing extensive cross-linking. Large immune complexes that cannot be cleared are deposited in vessel walls and induce an inflammatory response. The reaction can take hours, days, or even weeks to develop.

Some clinical examples:

* Rheumatoid arthritis
* Immune complex glomerulonephritis
* Serum sickness
* Subacute bacterial endocarditis
* Symptoms of malaria
* Systemic lupus erythematosus
* Arthus reaction
* Farmer's lung (Arthus-type reaction)

### Type 4 - cell-mediated (delayed-type hypersensitivity, DTH)[edit]

See also: Cell mediated immunity

Type 4 hypersensitivity is often called delayed type as the reaction takes two to three days to develop. Unlike the other types of hypersensitivity, it is mediated by T-cells rather than B-cells.

Type 4 reactions can be subdivided by the specific type of T-cell response that occurs when macrophages present antigen in a complex with either type 1 or 2 major histocompatibility complex.[4]

* Type 4a: T-helper (CD4+) Type 1 (TH1) T cells secrete interferon-gamma which activates macrophages to produce complement-fixing antibody isotypes. Rashes that are mediated by this type may be eczematous.
* Type 4b: T-helper (CD4+) Type 2 (TH2) T cells secrete the cytokines interleukin-4 and interleukin-5, which promote B-cell production of IgE and IgG4, macrophage deactivation, and mast-cell and eosinophil responses. Rashes that are mediated by this type may include bullae.
* Type 4c: Cytolytic T-cells (CD8+) (CTLs or TC cells) T cells secrete the cytokines performin and granzyme B. Rashes that are mediated by this type may include bullae and/or pustules.
* Type 4d: T-cells produce interleukin-8 which activates neutrophils. Rashes that are mediated by this type may include pustules.

Some clinical examples:

* Atopic dermatitis (eczema)
* Contact dermatitis. An example is the poison ivy rash, which is predominantly a Type 4a reaction.
* Celiac disease
* Chronic transplant rejection
* Leprosy
* Mantoux test
* Temporal arteritis
* Tuberculosis

### Type 5 - stimulatory[edit]

This is an additional type that is sometimes (often in Britain) used as a distinction from Type 2.[5]

Instead of binding to cell surface components, the antibodies recognize and bind to the cell surface receptors, which either prevents the intended ligand binding with the receptor or mimics the effects of the ligand, thus impairing cell signalling.

Some clinical examples:

* Graves disease
* Myasthenia gravis

## References[edit]

1. ↑ National Library of Medicine. Hypersensitivity. Retrieved on 2007-12-31.
2. ↑ Gell PGH, Coombs RRA, eds. Clinical Aspects of Immunology. 1st ed. Oxford, England: Blackwell; 1963.
3. ↑ Anonymous. Hypersensitivity, immediate. National Library of Medicine. Retrieved on 2008-01-16.
4. ↑ Pichler WJ (2003). "Delayed drug hypersensitivity reactions". Ann. Intern. Med. 139 (8): 683–93. PMID 14568857. [e]
5. ↑ Rajan TV (2003). "The Gell-Coombs classification of hypersensitivity reactions: a re-interpretation". Trends Immunol. 24 (7): 376–9. PMID 12860528. [e]