Immunological hypersensitivity reactions are immune responses that produce tissue damage. In 1963, a classification system was introduced by Gell and Coombs based on how immune reactions produced the damage, and to this day it has provided a framework for the understanding of immune effector mechanisms produced directly by antigen-specific responses or by the activation of innate immune mechanisms. It was updated in 2001 to introduce type subcategories of the type IV delayed hypersensitivity to describe cell-mediated allergy in the light of the recent knowledge of T-cell function. Although the classification system remains useful for describing mechanisms of tissue damage, the damage produced in an individual hypersensitivity reaction is usually produced by a mixture of mechanisms. The type I hypersensitivity mediated by IgE antibody to allergens in asthma and hay fever is, for example, typically accompanied by eosinophils from the Th2 type IVb responses.

Key Concepts

• Type I hypersensitivity consists of the IgE-mediated immediate hypersensitivity responses found in anaphylaxis and asthma attacks and slower responses caused by inflammatory cascades triggered by mediators released in the immediate reaction and by accompanying Th2 responses.
  
• Type II hypersensitivity is mediated by the direct effects of antibody and complement-mediated killing or opsonization.
  
• Type III hypersensitivity is mediated by the formation of antigen–antibody complexes that either activate complement for direct toxic effects or attract inflammatory cells, especially neutrophils that bind the complexes by Fc receptors and cause tissue damage.
  
• Type IV hypersensitivity can be subdivided depending on the type of T cell activated by the immune response.
  
• Type IVa corresponds to the classical monocytic tuberculin-type delayed hypersensitivity mediated by Th1 cells.
  
• Type IVb corresponds to the eosinophilic inflammation produced by Th2 cells.
  
• Type IVc corresponds to tissue damage produced by cytotoxic T cells and can have either granzyme B/perforin or Fas/FasL killing mechanisms.
  
• Type IVd hypersensitivity produces tissue damage by the infiltration of neutrophils attracted by T cells producing IL-8.
  
• Type V hypersensitivity categorizes the damage caused by agonist effects of antibodies binding to endocrine receptors.
  
• The tissue damage in individual hypersensitivity reactions is often caused by a mixture of the types of hypersensitivity reaction, for example, a combination of types I and IVa. IVb and IVc in contact hypersensitivity.