Roles of cytotoxic delayed-type hypersensitivity and macrophage-activating cell-mediated immunity in the pathogenesis of tuberculosis

Arthur M. Dannenberg

Research output: Contribution to journalArticle

Abstract

The tubercle bacillus is a facultative intracellular parasite that grows well in non-activated macrophages. When large numbers of these bacilli have grown intracellularly within such macrophages, a cytotoxic immune response, herein called tissue-damaging (or necrotizing) delayed-type hypersensitivity (DTH), kills the macrophages (and usually some of the surrounding tissue), forming the caseous center of the developing tubercle. In solid caseum, tubercle bacilli may survive, but do not multiply. When bacilli escape from the edge of the caseum, they are rapidly ingested by nearby viable macrophages. If these macrophages have not been activated, the bacilli again multiply intracellularly, and the cytotoxic immune response kills the bacilli-laden macrophages (and surrounding tissue), thus enlarging the caseous center. In hosts that develop poor activation of macrophages, this process is repeated until much of the lung is destroyed. In hosts that can develop good activation of macrophages (by cytokines from antigen-specific T cells), herein called cell-mediated immunity (CMI), the caseous centers become surrounded by these activated macrophages, which ingest and destroy the bacilli escaping from the caseum. This process can arrest the disease. Unfortunately, the caseous center may liquefy in such resistant hosts. In the liquefied menstruum, the bacilli may grow extracellularly (for the first time during the course of the disease), reaching tremendous numbers. The cytotoxic immune response to these numerous bacilli and their tuberculin-like products causes much tissue necrosis, including erosion of the walls of small bronchi, which results in cavity formation. From such cavities, the bacilli spread to other parts of the lung and to the environment. The extracellular multiplication of tubercle bacilli in the liquefied caseum is the main reason why tuberculosis perpetuates itself in mankind. It is also the reason why antimicrobial drug-resistant bacillary strains develop. To elucidate the various mechanisms involved in macrophage activation, caseation, and liquefaction is a major challenge for tuberculosis researchers today.

Original languageEnglish (US)
Pages (from-to)461-473
Number of pages13
JournalImmunobiology
Volume191
Issue number4-5
StatePublished - 1994

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Delayed Hypersensitivity
Cellular Immunity
Bacillus
Tuberculosis
Macrophages
Macrophage Activation
Lung
Tuberculin
Bronchi
Parasites
Necrosis
Research Personnel
Cytokines
T-Lymphocytes
Antigens

ASJC Scopus subject areas

  • Immunology

Cite this

Roles of cytotoxic delayed-type hypersensitivity and macrophage-activating cell-mediated immunity in the pathogenesis of tuberculosis. / Dannenberg, Arthur M.

In: Immunobiology, Vol. 191, No. 4-5, 1994, p. 461-473.

Research output: Contribution to journalArticle

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