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16.5: Delayed Hypersensitivities - Type IV

[ "article:topic", "authorname:kaiserg", "Type IV hypersensitivities" ]
  • Page ID
    3382
  • Skills to Develop

    1. Describe the mechanism for Type IV (delayed) hypersensitivity and give two examples.

    Delayed hypersensitivity is cell-mediated rather than antibody-mediated. The underlying  Mechanism of delayed hypersensitivity is the same mechanism as cell-mediated immunity. T8-lymphocytes become sensitized to an antigen and differentiate into cytotoxic T-lymphocytes while effector T4-lymphocytes become sensitized to an antigen and produce cytokines . CTLs, cytokines, eosinophils, and/or macrophages then cause harm rather than benefit (Fig. 1).

    u3fig2mtiv.jpgu3fig2ntiv.jpg

    Fig. 1: (left) Cytotoxic T-lymphocyte (CTL)-Induced Apoptosis of a Cross-Reacting Normal Cell during Type IV Hypersensitivity, step-1 (right) Binding of the CTL to a cross-reacting normal cell triggers the CTL to release pore-forming proteins called perforins, proteolytic enzymes called granzymes, and chemokines. Granzymes pass through the perforin pores and activate the enzymes that lead to apoptosis of the infected cell by means of destruction of its structural cytoskeleton proteins and by chromosomal degradation. As a result, the cell breaks into fragments that are subsequently removed by phagocytes.

    • CTLs use their TCR/CD8 to bind to peptide epitopes bound to MHC-I on infected cells or normal cells having cross-reacting epitopes and kill them through apoptosis.
    • TH1 cells activate macrophages causing the production of inflammatory cytokines and extracellular killing by the macrophages leading to tissue damage.
    • TH2 cells produce interleukin-4 (IL-4) and interleukin-5 (IL-5) to promote extracellular killing by eosinophils and causing tissue damage.

    Examples include:

    • the cell or tissue damage done during diseases like tuberculosis, leprosy, smallpox, measles, herpes infections, candidiasis, and histoplasmosis;
    • the skin test reactions seen for tuberculosis and other infections;
    • contact dermatitis like poison ivy;
    • type-1 insulin-dependent diabetes where CTLs destroy insulin-producing cells;
    • multiple sclerosis, where T-lymphocytes and macrophages secrete cytokines that destroy the myelin sheath that insulates the nerve fibers of neurons;
    • Crohn’s disease and ulcerative colitis; and
    • psoriasis.

    Delayed hypersensitivity also plays a major role in chronic transplant rejection as a result of CTL destruction of donor cells (host versus graft rejection) or recipient cells (graft versus host rejection). Immunosuppressive drugs such as cyclosporin A or FK-506 (Tacrolimus) are given in an attempt to prevent rejection. Both of these drugs prevent T-lymphocyte proliferation and differentiation by inhibiting the transcription of IL-2.

    Summary

    1. During delayed hypersensitivity,T8-lymphocytes become sensitized to an antigen and differentiate into cytotoxic T-lymphocytes (CTLs) while effector T4-lymphocytes become sensitized to an antigen and produce cytokines.
    2. CTLs, cytokines, eosinophils, and/or macrophages then cause harm rather than benefit.
    3. Examples include the cell or tissue damage done during diseases like tuberculosis, leprosy, smallpox, measles, herpes infections, candidiasis, and histoplasmosis, the skin test reactions seen for tuberculosis and other infections, contact dermatitis like poison ivy, type-1 insulin-dependent diabetes where CTLs destroy insulin-producing cells, multiple sclerosis, where T-lymphocytes and macrophages secrete cytokines that destroy the myelin sheath that insulates the nerve fibers of neurons, and Crohn’s disease and ulcerative colitis.

    Questions

    Study the material in this section and then write out the answers to these questions. Do not just click on the answers and write them out. This will not test your understanding of this tutorial.

    1. Describe the mechanism for Type IV (delayed) hypersensitivity and give 2 examples. (ans)

    Contributors

    • Dr. Gary Kaiser (COMMUNITY COLLEGE OF BALTIMORE COUNTY, CATONSVILLE CAMPUS)