Hypersensitivity reaction

Hypersensitivity reactions are the immunological response to both exogenous and endogenous antigens, and form the basis for many diseases. 

Pathology

Classification

Using the Gell and Coombs' classification, there are four types of hypersensitivity reactions, each mediated by a different mechanism. In the past twenty years there have been modifications of the original classification in order to incorporate revised understandings of the immune system and its responses  ^1-4,10: 

• type I hypersensitivity: immediate reaction
  • IgE mediated
  • binds to Fc membrane receptor on mast cells and interacts with corresponding antigen
  • mast cell degranulation occurs on following exposure ⁸
    • urticaria
    • ​asthma
    • allergy/anaphylaxis
• type II hypersensitivity: antibody mediated reaction
  • IgG/IgM mediated
  • causes cell destruction and disrupts cell function ⁵
    • autoimmune haemolytic anaemia
    • Goodpasture syndrome
    • rheumatic heart disease ⁹
• type III hypersensitivity: immune-complex mediated reaction
  • IgG/IgM mediated
  • antibody-antigen Immunocomplex deposition
  • these can activate complement, cause release of chemotactic and clotting factor and trigger phagocytosis
    • vasculitis ⁶ 
    • systemic lupus erythematosus (SLE)
    • hypersensitivity pneumonitis
• type IV hypersensitivity: cell-mediated reaction
  • 'delayed' hypersensitivity
  • T-helper cells secrete various different cytokines resulting in different immune reactions
    •  interferon y secreted by T-helper type 1, which activate macrophages leading production of complement-fixing antibody isotypes stimulating inflammatory responses
      • CD8+  T-cell mediated killing of cells expressing reactive antigen in association with MHC-1
    • IL-4, IL-5, IL-13 secreted by T-helper type 2
      • stimulate B cell activation and production of immunoglobulins (IgE), mast cell and eosinophil reactions and macrophage deactivation
    • other T-cells contain granules performing cytotoxic functions by the release of perforin/granzymes directly killing the infected cells ⁷
      • contact dermatitis
      • coeliac disease
      • transplant rejection
      • type 1 diabetes mellitus
      • multiple sclerosis

History and etymology

Robin Coombs and Philip George Houthem Gell, British immunologists, first described their eponymous classification system of hypersensitivity reactions in their seminal textbook "Clinical Aspects of Immunology", which was first published in 1963 ^11,12. Coombs is also rememberremembered by generations of medical students and doctors for his eponymous antiglobulin test ¹¹.