Hypersensitivity: T Lymphocyte Mediated (Type IV)


Five types of hypersensitivity reactions have been described: types I, II, III and V depend on antigen antibody interactions and have been termed ‘immediate’ and type IV reactions depend on interaction of antigen with T lymphocytes and has been called ‘delayed‐type hypersensitivity’, or DTH. The DTH reaction involves cellular activation of T helper cells (CD4+) and/or cytotoxic T cells (CD8+CTLs). Subsequent cytokine secretion gives rise to distinct pathologies. In many cases, sustained release of antigen and continued activation of sensitized T lymphocytes result in amplification of responses that provoke excessive immune activation. These events are the basis for development of a broad range of inflammatory pathologies that include erythema and oedema, granuloma formation, extended development of fibrosis, and tissue necrosis.

Key Concepts

  • Type IV hypersensitivity (also called delayed‐type hypersensitivity, DTH) represents immune reactivity where T lymphocytes have had prior encounter with antigen.
  • It is termed ‘delayed‐type’ hypersensitivity because the reaction usually manifests 12–24 h post antigen exposure.
  • DTH responses can manifest from contact with allergens or infectious agents, giving rise to localised inflammation, erythema and oedema.
  • The classical manifestations of DTH are defined as cutaneous (contact), tuberculin or granulomatous hypersensitivity. Broader classification now includes subdivision based on dominant effector activity and defined elicited pathology.
  • DTH evolved as a protective host mechanism to combat pathogens; however, excessive DTH responses can lead to immunopathology, exhibited by granuloma formation, fibrosis or even tissue necrosis.
  • DTH reactions are prominent in autoimmune diseases, and have also been demonstrated to play a role in the response to transplantation of tissue from a genetically different donor (allogeneic transplantation).

Keywords: delayed‐type hypersensitivity; DTH ; granuloma; antigen; hapten; T lymphocytes

Figure 1. Erythema and induration at the site of intradermal injection of PPD in a patient previously infected with M. tuberculosis. A positive reaction of more than 10 mm indicates reactivity in immune competent individuals. Reproduced with permission from Roitt I © Blackwell Publishing Ltd, .
Figure 2. Histological manifestation of allergic contact dermatitis. Histopathology due to extended contact with antigens in the dermis results in destructive delayed‐type hypersensitive responses. Perivascular infiltrates of activated lymphocytes and macrophages are evident in the dermis, with fibrosis due to prolonged exposure and release of proinflammatory mediators (a). High power magnification reveals activated mononuclear cell infiltration, thickened endothelial cell walls and fibrotic events (b). The material photographed was provided by Dr. Ronald P. Rapini, Department of Dermatology, University of Texas‐Houston Medical School, Houston, Texas.
Figure 3. Mycobacterial granuloma within lung tissue demonstrating caseating pathology with necrotic center surrounded by active macrophages, lymphocytes and multinucleated giant cells. T lymphocytes, characteristic of the DTH response, are necessary for containment, as well as for assisting in activation of macrophages for elimination of organisms. The material photographed was provided by Dr. Robert L. Hunter, Jr., Department of Pathology, University of Texas‐Houston Medical School, Houston, Texas.


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Further Reading

Abbas AK and Lichtman AH (2011) Effector mechanisms of T cell‐mediated immune reactions. In: Abbas AK and Lichtman AH (eds) Cellular and Molecular Immunology, 7th edn, pp. 225–242. Philadelphia: W. B. Saunders.

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Black CA (1999 May) Delayed type hypersensitivity: current theories with an historic perspective. Dermatology Online Journal 5 (1): 7.

Coico R and Sunshine G (2009) Hypersensitivity: Type IV. In: Coico R and Sunshine G (eds) Immunology: A short course, 6th edn, pp. 247–254. Hoboken: John Wiley & Sons, Inc..

Owen J , Punt J and Stranford S (eds) (2013) Kuby Immunology, 7th (Hypersensitivity Reactions) edn, pp. 393–400. New York: W.H. Freeman and Company.

Kumar V , Abbas AK , Fausto N and Mitchell RN (eds) (2013) Robbins Basic Pathology, 9th (Diseases of the Immune System) edn, pp. 99–160. Philadelphia: Saunders.

Murphy K , Travers P and Walport M (eds) (2012) Janeway's Immunobiology, 8th (Allergy and Allergic Disease) edn. New York: Garland Science.

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Hwang, Shen‐An, and Actor, Jeffrey K(Aug 2015) Hypersensitivity: T Lymphocyte Mediated (Type IV). In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0001139.pub3]