Hypersensitivity: T Lymphocyte‐mediated (Type IV)

Jeffrey K Actor, University of Texas‐Houston Medical School, Houston, Texas, USA
Neil M Ampel, University of Arizona, Tucson, Arizona, USA

Published online: December 2009

DOI: 10.1002/9780470015902.a0001139.pub2

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 (1998).
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.
close
 References
    book Actor JK, Hunter RLJ, Jagannath C et al. (2007) "Immunopathology of tuberculosis". In: Zander DS, Popper HH, Jagirdar J, Haque AK, Cagle PT and Barrios R (eds) Molecular Pathology of Lung Diseases, p. 419. Florissant, MO: Springer.
    Ahmed AR and Blose DA (1983) Delayed-type hypersensitivity skin testing. A review. Archives of Dermatology 119(11) : 934–945.
    Almeida SR (2008) Immunology of dermatophytosis. Mycopathologia 166(5–6) : 277–283.
    Blatt SP, Hendrix CW, Butzin CA et al. (1993) Delayed-type hypersensitivity skin testing predicts progression to AIDS in HIV-infected patients. Annals of International Medicine 119(3) : 177–184.
    Buchanan KL and Murphy JW (1997) Kinetics of cellular infiltration and cytokine production during the efferent phase of a delayed-type hypersensitivity reaction. Immunology 90(2) : 189–197.
    Centers for Disease Control and Prevention (1997) Anergy skin testing and tuberculosis [corrected] preventive therapy for HIV-infected persons: revised recommendations. MMWR. Recommendations and Reports 46(RR-15) : 1–10.
    Chu CQ, Field M, Allard S et al. (1992) Detection of cytokines at the site of tuberculin-induced delayed-type hypersensitivity in man. Clinical and Experimental Immunology 90(3) : 522–529.
    Dolan MJ, Clerici M, Blatt SP et al. (1995) In vitro T cell function, delayed-type hypersensitivity skin testing, and CD4+ T cell subset phenotyping independently predict survival time in patients infected with human immunodeficiency virus. Journal of Infectious Diseases 172(1) : 79–87.
    Dvorak HF, Mihm MC Jr., Dvorak AM et al. (1974) Morphology of delayed type hypersensitivity reactions in man. I. Quantitative description of the inflammatory response. Laboratory Investigation 31(2) : 111–130.
    Flynn JL and Chan J (2001) Immunology of tuberculosis. Annual Review of Immunology 19: 93–129.
    Higashi N, Yoshizuka N, Ohuchi A et al. (1995) Involvement of inflammatory cytokines in a delayed-type hypersensitivity reaction. Cellular Immunology 161(2) : 288–294.
    Hunter RL, Jagannath C, Actor JK et al. (2007) Pathology of postprimary tuberculosis in humans and mice: contradiction of long-held beliefs. Tuberculosis (Edinburgh) 87(4) : 267–278.
    Iwakura Y, Nakae S, Saijo S et al. (2008) The roles of IL-17A in inflammatory immune responses and host defense against pathogens. Immunological Review 226: 57–79.
    Kobayashi K, Kaneda K, Kasama T et al. (2001) Immunopathogenesis of delayed-type hypersensitivity. Microscopy Research and Technique 53(4) : 241–245.
    Lockey RF (1995) Adverse reactions associated with skin testing and immunotherapy. Allergy Proceedings 16(6) : 293–296.
    North RJ and Jung YJ (2004) Immunity to tuberculosis. Annual Review of Immunology 22: 599–623.
    Ode-Hakim S, Docke WD, Kern F et al. (1996) Delayed-type hypersensitivity-like mechanisms dominate late acute rejection episodes in renal allograft recipients. Transplantation 61(8) : 1233–1240.
    Posadas SJ and Pichler WJ (2007) Delayed drug hypersensitivity reactions – new concepts. Clinical and Experimental Allergy 37(7) : 989–999.
    Poulter LW, Seymour GJ, Duke O et al. (1982) Immunohistological analysis of delayed-type hypersensitivity in man. Cellular Immunology 74(2) : 358–369.
    book Roitt I (1998) Essential Immunology. Oxford: Blackwell Scientific.
    Schwartz RH (2003) T cell anergy. Annual Review of Immunology 21: 305–334.
    Sokal JE (1975) Editorial: measurement of delayed skin-test responses. New England Journal of Medicine 293(10) : 501–502.
    Spierings E, de Boer T, Wieles B et al. (2000) The role of Schwann cells, T cells and Mycobacterium leprae in the immunopathogenesis of nerve damage in leprosy. Leprosy Review 71(suppl.) : S121–S129.
    Toebak MJ, Gibbs S, Bruynzeel DP et al. (2009) Dendritic cells: biology of the skin. Contact Dermatitis 60(1) : 2–20.
    Youssef AR, Otley C, Mathieson PW et al. (2002) Effector mechanisms in murine allograft rejection: comparison of skin and heart grafts in fully allogeneic and minor histocompatibility antigen-mismatched strain combinations. Transplant International 15(6) : 302–309.
 Further Reading
    book 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.
    book 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.
    book 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.
    book 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.
    book 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.
    book 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.

Related Sub-Topics:

Cells of the Immune System | Diagnostics, Therapeutics and Methods | Allergy and Hypersensitivity
Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

Article Title: Hypersensitivity: T Lymphocyte‐mediated (Type IV)
 
How to Cite close
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]