M. tuberculosis: immunology and vaccination
2001
Tuberculosis is increasing. Current treatment regimens require at least
6 months, because latent or stationary phase organisms are difficult to kill.
Such regimens do not achieve full compliance, and “directly observed
therapy short course” (DOTS) is having less impact than expected.
This worrying situation is aggravated by coinfection with human immunodeficiency
virus (HIV), and by the increase in drug-resistant strains. We need new insights that lead to more rapid therapies and immunotherapies,
and more reliable vaccines. Recent insights have come from: understanding of the relationship between Mycobacterium tuberculosis and macrophages; the multiple T cell types
that recognise mycobacterial peptides, lipids and glycolipids; the critical
role of interferon‐γ (IFNγ) and interleukin‐12 (IL‐12)
in human mycobacterial infection revealed by genetically defective children;
quantitation of the presence and importance of Th2 lymphocyte activation in
human tuberculosis; the role of local conversion of inactive cortisone to
active cortisol in the lesions; the recognition that some effective prophylactic
vaccines also work as immumotherapeutics whereas others do not. In the longer
term the recent sequencing of the M. tuberculosis genome will lead
to further advances. In the short term, effective immunotherapy remains the most accessible
breakthrough in the management of tuberculosis. The types of practical advance
that will result from sequencing the genome are discussed speculatively, but
cannot yet be predicted with certainty.
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