Hypersensitivity: T Lymphocyte‐mediated (Type IV)


Five types of hypersensitivity reactions have been described: types I, II, III and V depend on the interaction of antigen with antibody and have been termed immediate; type IV depends on the 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 cells results in amplification of responses that provoke excessive macrophage activation. These events are the basis for development of a broad range of inflammatory pathologies which range from erythema and oedema to granuloma formation, to extended development of fibrosis and even tissue necrosis.

Key Concepts:

  • Type IV hypersensitivity (also called delayed‐type hypersensitivity, DTH) represents immune reactivity where lymphocytes have had prior encounter with antigen.

  • The DTH is conferred by sensitized T lymphocytes, but not by serum factors.

  • The DTH reaction involves T lymphocyte interactions with antigen culminating in cellular recruitment and activation, and subsequent cytokine secretion.

  • Because the T cell‐mediated responses require induced synthesis of effector molecules they develop more slowly, thus they are termed ‘delayed‐type’ hypersensitive responses.

  • DTH responses can manifest from contact with allergens or infectious agents, giving rise to localized inflammation, erythema and oedema.

  • The classical manifestations of DTH are defined as cutaneous (contact), tuberculin or granulomatous hypersensitivity.

  • The 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: adjuvant; granuloma; antigen; hyper sensitivity; DTH

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. From Roitt .

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 (left). High‐power magnification reveals activated mononuclear cell infiltration, thickened endothelial cell walls and fibrotic events (right). Courtesy of 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. Courtesy of 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 (2009) Effector mechanisms of T cell‐mediated immune reactions. In: Abbas AK and Lichtman AH (eds) Cellular and Molecular Immunology, 6th edn. Philadelphia: W. B. Saunders.

Barnetson R, Gawkrodger D and Britton W (2006) Type IV hypersensitivity. In: Male D, Brostof J, Roth D and Roitt R (eds) Immunology, 7th edn. London: Mosby.

Black CA (1999) 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: Wiley.

Kindt TJ, Goldsby RA and Osborne BA (2006) Hypersensitivity reactions. In: Kindt TJ, Goldsby RA and Osborne BA (eds) Kuby Immunology, 6th edn, pp. 393–400. New York: W.H. Freeman and Company.

Kumar V, Abbas AK, Fausto N and Mitchell RN (2008) Diseases of the immune system. In: Kumar V, Abbas AK, Fausto N and Mitchell RNM (eds) Robbins Basic Pathology, 8th edn, pp. 128–135. Philadelphia: Saunders.

Murphy K, Travers P and Walport M (2008) Allergy and hypersensitivity. In: Murphy K, Travers P and Walport M (eds) Janeway's Immunobiology, 7th edn, pp. 555–598. New York: Garland Science.

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Actor, Jeffrey K, and Ampel, Neil M(Dec 2009) Hypersensitivity: T Lymphocyte‐mediated (Type IV). In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0001139.pub2]