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12.4E: Type IV (Delayed Cell-Mediated) Reactions

  • Page ID
    11850
  • Type IV hypersensitivity reactions are cell-mediated and take 2 to 3 days to develop.

    LEARNING OBJECTIVES

    Describe Type IV cell-mediated reactions and explain why they take two to three days to develop

    KEY TAKEAWAYS

    Key Points

    • Cell-mediated immunity is an immune response that does not involve antibodies but rather involves the activation of phagocytes, natural killer cells (NK), antigen -specific cytotoxic T-lymphocytes, and the release of various cytokines in response to an antigen.
    • In type IV hypersensitivity reactions, CD4+ helper T cells recognize antigen in a complex with Class 2 major histocompatibility complex on macrophages (the antigen-presenting cells).
    • A classic example of delayed type IV hypersensitivity is the Mantoux tuberculin test in which skin induration indicates exposure to tuberculosis.

    Key Terms

    • cellular immunity: Cellular immunity protects the body by: activating antigen-specific cytotoxic T-lymphocytes, activating macrophages and natural killer cells and stimulating cytokine secretion to stimulate other cells involved in adaptive immune responses and innate immune responses.
    • type IV hypersensitivity: A cell-mediated immune response that takes two to three days to develop.

    Cell-mediated immunity is an immune response that does not involve antibodies, but rather involves the activation of phagocytes, natural killer cells (NK), antigen-specific cytotoxic T-lymphocytes, and the release of various cytokines in response to an antigen. Historically, the immune system was separated into two branches: humoral immunity, for which the protective function of immunization could be found in the humor (cell-free bodily fluid or serum) and cellular immunity, for which the protective function of immunization was associated with cells. CD4 cells or helper T cells provide protection against different pathogens. Cytotoxic T cells cause death by apoptosis without using cytokines. Therefore in cell mediated immunity cytokines are not always present.

    Cellular immunity protects the body by:

    1. activating antigen-specific cytotoxic T-lymphocytes that are able to induce apoptosis in body cells displaying epitopes of foreign antigen on their surface, such as virus-infected cells, cells with intracellular bacteria, and cancer cells displaying tumor antigens

    2. activating macrophages and natural killer cells, enabling them to destroy pathogens

    3. stimulating cells to secrete a variety of cytokines that influence the function of other cells involved in adaptive immune responses and innate immune responses

    Cell-mediated immunity is directed primarily at microbes that survive in phagocytes and microbes that infect non-phagocytic cells. It is most effective in removing virus-infected cells, but also participates in defending against fungi, protozoans, cancers, and intracellular bacteria. It also plays a major role in transplant rejection.

    Type IV hypersensitivity is often called delayed type hypersensitivity as the reaction takes two to three days to develop. Unlike the other types, it is not antibody mediated but rather is a type of cell-mediated response. CD4+ helper T cells recognize antigen in a complex with Class 2 major histocompatibility complex. The antigen-presenting cells in this case are macrophages that secrete IL-12, which stimulates the proliferation of further CD4+ Th1 cells. CD4+ T cells secrete IL-2 and interferon gamma, further inducing the release of other Th1 cytokines, thus mediating the immune response. Activated CD8+ T cells destroy target cells on contact, whereas activated macrophages produce hydrolytic enzymes and, on presentation with certain intracellular pathogens, transform into multinucleated giant cells.

    A classic example of delayed type IV hypersensitivity is the Mantoux tuberculin test in which skin induration indicates exposure to tuberculosis. Other examples include: temporal arteritis, Hashimoto’s thyroiditis, symptoms of leprosy, symptoms of tuberculosis, coeliac disease, graft-versus-host disease and chronic transplant rejection.

    image

    Mantoux test: The reaction is read by measuring the diameter of induration (palpable raised, hardened area) across the forearm (perpendicular to the long axis) in millimeters. If there is no induration, the result should be recorded as “0 mm”. Erythema (redness) should not be measured. If a person has had a history of a positive tuberculin skin test, or had a recent tuberculin skin test (within one year), another skin test should be used.

    image

    Mantoux tuberculin test: The Mantoux test (also known as the Mantoux screening test, tuberculin sensitivity test, Pirquet test, or PPD test for purified protein derivative) is a diagnostic tool for tuberculosis. A standard dose of tuberculin is injected intradermally (between the layers of dermis) and read 48 to 72 hours later.

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