Hypersensitivity: T Lymphocyte Mediated (Type IV)

Abstract

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).