The pathogenesis of tuberculosis

Tuberculosis patients relapse if treatment is not continued for 6 months, because chemotherapy fails to convert the patients' response from the necrotizing pattern characteristic of disease (Koch phenomenon) to the nonnecrotizing bactericidal function required for optimal immunity. We need to understand the nature of these two immunological states and how to convert one to the other. Studies in mice and humans implicate differences in cytokine profiles and in metabolism of adrenal steroids. Either enhanced susceptibility or protection can be evoked in mice with appropriate doses of a killed environmental saprophyte. This emphasizes the importance of shared epitopes and may explain the geographically variable efficacy of Mycobacterium bovis Bacillus Calmette Guérin vaccination. Unlike soluble antigens of M. tuberculosis itself, which tend to evoke necrosis, the shared mycobacterial epitopes evoke little skin-test reactivity in patients. Preparations of these epitopes show potential as immunotherapeutic agents to convert the response from necrotic to bactericidal mode.