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Chapter 13 : Delayed-Type Hypersensitivity

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Abstract:

Delayed-type hypersensitivity (DTH) reactions are variations on a theme of chronic inflammation; they are in vivo reactions, which, because of the time course and complexity of the different cell types involved, cannot be duplicated in vitro. DTH reactions are particularly effective against intracellular parasites that can replicate within macrophages, such as mycobacteria and listeria, as well as against other organisms for which the major clearing mechanism is activation of macrophages, such as Candida albicans, Treponema pallidum, and many viruses. The diseases caused by superantigens are listed in this chapter. The classic example of a DTH skin test is the delayed-type tuberculin skin reaction. It is elicited in sensitive individuals by intradermal injection of tuberculoprotein antigens. Cutaneous basophil hypersensitivity (CBH) reactions require specifically sensitized lymphocytes. Protection against reinfection may be partially mediated by antibody neutralization of organisms, but macrophages activated by a delayed hypersensitivity reaction appear to be the most effective way of killing the organism. The human disease takes three forms: acute hemorrhagic encephalomyelitis, acute disseminated encephalomyelitis, and multiple sclerosis. These three forms are discussed in detail in this chapter. TCTL-cell killing of virus-infected cells appears to be the most efficient way of eliminating virus-infected cells. TCTL cells may lyse incompetent macrophages that contain bacilli that they are unable to digest. The microorganisms are thus released into a toxic extracellular environment or are made available for phagocytosis by fully competent macrophages. In this way, intracellular organisms that may persist in a protected niche are booted out and destroyed.

Citation: Sell S. 2001. Delayed-Type Hypersensitivity, p 431-451. In Immunology, Immunopathology, and Immunity, Sixth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818012.ch13
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Figures

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Figure 13.1

DTH reactions. Specifically sensitized TDTH cells are activated by reaction with antigen on cells or soluble antigen to release interleukins (TNF, IL-2, and IFN-γ), which attract and activate macrophages. Activated macrophages produce TNF-α, IL-1, IL-6, and prostaglandin E2, which contribute to the late phase of the DTH reactions as well as phagocytose and digest cells and tissue debris. The activation of the macrophages is effective in clearing macrophages of intracellular infections, such as tuberculosis, leprosy, leishmaniasis, and viruses, as well as for phagocytosis and destruction of extracellular infections, such as in syphilis and candidiasis.

Citation: Sell S. 2001. Delayed-Type Hypersensitivity, p 431-451. In Immunology, Immunopathology, and Immunity, Sixth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818012.ch13
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Image of Figure 13.2
Figure 13.2

Hypothetical reaction of staphylococcal enterotoxin with the class II MHC T-cell receptor. The toxins (superantigens) react with the class II MHC β chain, away from the antigen-binding groove and the Vβ chain of the T-cell receptor, and act as a clamp, bringing into close apposition the surfaces of the T-cell receptor and the MHC. This mimics the effect of the contact that occurs during T-cell recognition of antigen through conventional binding in the antigen groove of the MHC. J, D, V, chains of the cell receptor; α and β, chains of the MHC; Ag, the antigen-binding groove of class II MHC.

Citation: Sell S. 2001. Delayed-Type Hypersensitivity, p 431-451. In Immunology, Immunopathology, and Immunity, Sixth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818012.ch13
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Image of Figure 13.3
Figure 13.3

Evolution of the delayed skin reaction. In normal skin, lymphocytes pass from venules through the dermis to lymphatics, which return these cells to the circulation. Development of a delayed skin reaction involves recognition of antigen by sensitized lymphocytes (T cells), immobilization of lymphocytes at the site, production and release of lymphocyte mediators, and accumulation of macrophages with eventual destruction of antigen and resolution of the reaction. This results in an accumulation of cells seen at 24 to 48 h after antigen injection. Macrophages degrade the antigen. When the antigen is destroyed, the reactive cells are either destroyed or returned via the lymphatics to the bloodstream or draining lymph nodes. In this way, specifically sensitized lymphocytes may be distributed throughout the lymphoid system after local stimulation with antigen.

Citation: Sell S. 2001. Delayed-Type Hypersensitivity, p 431-451. In Immunology, Immunopathology, and Immunity, Sixth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818012.ch13
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Image of Figure 13.4
Figure 13.4

Progression of the primary chancre of syphilis. Infection with T. pallidum occurs by inoculation through abraded skin or mucous membrane. After inoculation, there is systemic dissemination of the organisms as well as local proliferation at the site of infection. Hyperplasia of draining lymph nodes (lymphadenopathy) signifies an active immune response. Both sensitized cells and humoral antibody are produced. The primary lesion, which is a firm, elevated skin lesion with central necrosis, is a manifestation of a delayed hypersensitivity reaction. T cells infiltrate first, followed by macrophages, which phagocytose and destroy the infecting organisms. Viable organisms remain in “protective niches” in the body, giving rise to secondary, latent, and tertiary disease.

Citation: Sell S. 2001. Delayed-Type Hypersensitivity, p 431-451. In Immunology, Immunopathology, and Immunity, Sixth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818012.ch13
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Figure 13.5

Pathogenic events in experimental allergic encephalomyelitis. Immunization of experimental animals with myelin or encephalitogenic protein results in production of humoral antibody and specifically sensitized cells, which together lead to demyelination by macrophages. Antibody reacting with myelin released into circulation through endothelial venules in white matter (i.e., myelinated area of brain and spinal cord) activates either anaphylatoxin (complement) or mast cell (immunoglobulin E) degranulation. Contraction of endothelial cells opens up gaps in small venule walls. Sensitized small TDTH lymphocytes move into white matter, react with myelin antigen, and release lymphocyte mediators. Macrophages, attracted and activated by these mediators, phagocytose and digest antibody-coated myelin or myelin affected by reaction with sensitized lymphocytes. If zones of demyelination are large, fibrosis will occur, and permanent loss of function will result.

Citation: Sell S. 2001. Delayed-Type Hypersensitivity, p 431-451. In Immunology, Immunopathology, and Immunity, Sixth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818012.ch13
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Tables

Generic image for table
Table 13.1

Diseases caused by superantigens a

Citation: Sell S. 2001. Delayed-Type Hypersensitivity, p 431-451. In Immunology, Immunopathology, and Immunity, Sixth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818012.ch13
Generic image for table
Table 13.2

Pathogenesis of some virus-related encephalitides of animals

Citation: Sell S. 2001. Delayed-Type Hypersensitivity, p 431-451. In Immunology, Immunopathology, and Immunity, Sixth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818012.ch13
Generic image for table
Table 13.3

Viral encephalitides of humans

Citation: Sell S. 2001. Delayed-Type Hypersensitivity, p 431-451. In Immunology, Immunopathology, and Immunity, Sixth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818012.ch13

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