Experimental approaches to mechanisms of protection and pathogenesis in M. tuberculosis infection

B. R. Bloom, J. Flynn, K. McDonough, Y. Kress, John Chan

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

It has, for many years, been widely assumed that the fundamental mechanism of protection in tuberculosis infection is a CD4 T cell response producing lymphokines that activate macrophages to kill or restrict the intracellular growth of M. tuberculosis. Just as certain cytokines, e.g. IFN-γ, are currently perceived to be important for protection, others, particularly tumor necrosis factor (TNF), are thought to be responsible for much of the tissue destruction associated with the disease. Yet there are remarkably few critical experimental or clinical data that have defined the immunological requirements for protection and pathogenesis. One of the initial stimuli to the work we have undertaken has been careful reflection on the results of the many prospective trials of BCG against tuberculosis. Two aspects have impelled us to reconsider conventional wisdom. The first, of course, is the wide discrepancy in the degree of protection imparted, ranging from 0% in South India to 77% in the British MRC trial (1, 2). The second is that, in all trials that examined them, skin test conversions to tuberculin positivity were 85% or greater, indicating a disparity between the presence of delayed hypersensitivity to tuberculin and protection. We and others have argued (1, 2) that there are multiple possible explanations for this discrepancy, the principal one being protection caused by infection with environmental mycobacteria. But, the general point raised is whether cell mediated immunity as manifested by CD4<sup>+</sup> cell production of lymphokines and macrophage activation is a sufficient mechanism for protection against M. tuberculosis infection.

Original languageEnglish (US)
Pages (from-to)526-536
Number of pages11
JournalImmunobiology
Volume191
Issue number4-5
StatePublished - 1994

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Tuberculosis
Lymphokines
Tuberculin
Infection
Macrophage Activation
Delayed Hypersensitivity
Mycobacterium
Mycobacterium bovis
Skin Tests
Cellular Immunity
India
Tumor Necrosis Factor-alpha
Macrophages
Cytokines
T-Lymphocytes
Growth

ASJC Scopus subject areas

  • Immunology

Cite this

Experimental approaches to mechanisms of protection and pathogenesis in M. tuberculosis infection. / Bloom, B. R.; Flynn, J.; McDonough, K.; Kress, Y.; Chan, John.

In: Immunobiology, Vol. 191, No. 4-5, 1994, p. 526-536.

Research output: Contribution to journalArticle

Bloom, BR, Flynn, J, McDonough, K, Kress, Y & Chan, J 1994, 'Experimental approaches to mechanisms of protection and pathogenesis in M. tuberculosis infection', Immunobiology, vol. 191, no. 4-5, pp. 526-536.
Bloom, B. R. ; Flynn, J. ; McDonough, K. ; Kress, Y. ; Chan, John. / Experimental approaches to mechanisms of protection and pathogenesis in M. tuberculosis infection. In: Immunobiology. 1994 ; Vol. 191, No. 4-5. pp. 526-536.
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