Hypersensitivity reactions are exaggerated or inappropriate immunologic responses occurring in response to an antigen or allergen. Gell and Coombs described four classes in 1963:
- Type I hypersensitivity reactions
- Type II hypersensitivity reactions
- Type III hypersensitivity reactions
- Type IV hypersensitivity reactions
Type I hypersensitivity reactions
Type I hypersensitivity reactions are allergic reactions provoked by re-exposure to a specific antigen called the allergen. These reactions are mediated by IgE and tend to occur 15 to 30 minutes from the time of exposure to the allergen. Contact with a “sensitised” antigen crosslinks IgE bound to mast cells and basophils, causing the release of vasoactive mediators.
The following are examples of type I hypersensitivity reactions:
- Anaphylaxis
- Angioedema
- Urticaria
- Allergic rhinoconjunctivitis
- Allergic asthma
- Atopic dermatitis
Anaphylaxis is an example of a type I hypersensitivity reaction. The response is caused by the binding of an antigen to an antigen-specific antibody leading to mast cell degranulation. Histamine and other mediators, including leukotrienes, tumour necrosis factor and various cytokines, are released from mast cells and basophils following exposure to this antigen.
Anaphylaxis requires prior exposure to the antigen. Upon the initial exposure, there is a sensitisation reaction, and it is only on second exposure to the antigen that anaphylaxis occurs. Mast cell degranulation occurs due to massive calcium influx into the cells.
Type II hypersensitivity reactions
Type II hypersensitivity reactions, also known as cytotoxic hypersensitivity, occur when antibodies produced by the immune response bind to antigens on the patient’s own cell surfaces. Antigens on host cells are perceived as foreign, tagged with IgG or IgM and destroyed by the membrane attack complex MAC and phagocytosis.
The following are examples of type II hypersensitivity reactions:
- Autoimmune haemolytic anaemia
- Haemolytic disease of the newborn
- ANCA associated vasculitides
- Goodpasture’s syndrome
- Myasthenia gravis
- Rhesus incompatibility
Type III hypersensitivity reactions
Type III hypersensitivity reactions are caused by the accumulation of insoluble antigen-antibody complexes that are not adequately cleared by innate immune cells in various tissues. These antigen-antibody complexes are then deposited in tissues, where they activate complement, neutrophil infiltration, and an inflammatory response.
The following are examples of type III hypersensitivity reactions:
- Immune complex glomerulonephritis
- Rheumatoid arthritis
- Systemic lupus erythematosus
- Serum sickness
- Arthus reaction
- Extrinsic allergic alveolitis
Type IV hypersensitivity reactions
Type IV hypersensitivity reactions, also known as cell-mediated or delayed-type hypersensitivity, are a type of cell-mediated response that is mediated by specific subsets of CD4+ or CD8+ cytotoxic T cells. They are also known as delayed-type hypersensitivity reactions, as they can take several days to develop.
The following are examples of type IV hypersensitivity reactions:
- Allergic contact dermatitis
- Mantoux test
- Multiple sclerosis
- Chronic transplant rejection
- Hashimoto’s thyroiditis
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