TY - JOUR
T1 - Roles of Cytotoxic Delayed-Type Hypersensitivity and Macrophage-Activating Cell-Mediated Immunity in the Pathogenesis of Tuberculosis
AU - Dannenberg, Arthur M.
N1 - Funding Information:
Many of these principles concerning the pathogenesis of tuberculosis were established by MAX B. LURIE, with whom the author spent 12 years at the University of Pennsylvania. His insight into the mechanisms of this disease was both penetrating and comprehensive. The author appreciates the superb editorial assistance of ILSE M. HARROP, and the financial support of grant AI-27165 from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland; the Johns Hopkins Environmental Health Sciences Center grant ES-03819, from the National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina; and grant HL-10342, from the National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland. Figures 1 to 6 are reprinted from reference 4 with permission from the American Society of Microbiology.
PY - 1994
Y1 - 1994
N2 - 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 antigenspecific 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.
AB - 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 antigenspecific 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.
UR - http://www.scopus.com/inward/record.url?scp=0028148997&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0028148997&partnerID=8YFLogxK
U2 - 10.1016/S0171-2985(11)80452-3
DO - 10.1016/S0171-2985(11)80452-3
M3 - Article
C2 - 7713560
AN - SCOPUS:0028148997
SN - 0171-2985
VL - 191
SP - 461
EP - 473
JO - Immunobiology
JF - Immunobiology
IS - 4-5
ER -