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Chapter 29 : Immune Intervention in Tuberculosis
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Regardless of the theoretical attraction of immune intervention in tuberculosis and although Mycobacterium bovis Bacille Calmette Guérin (BCG) provides a mainstay of global vaccination campaigns, current efforts in tuberculosis control are almost exclusively directed toward implementation of antimicrobial therapy. This chapter reviews the prospects for changing this situation by developing improved immune interventions. BCG provides some hard lessons for would-be developers of new tuberculosis vaccines. On the positive side, it vindicates the concept of vaccination as an approach to tuberculosis control. While precise numbers are hard to obtain, it seems reasonable to extrapolate that BCG has saved the lives of millions of potential victims of childhood tuberculosis. In experimental-animal models, BCG vaccination conforms to this paradigm. In naïve animals, the population of M. tuberculosis increases for several weeks after infection before being brought under the control of the immune response. Mycobacteria provide a potent signal to the innate immune system, with cell wall components triggering scavenger and Toll-like receptors on the cell surface, activating NF-κB transduction pathways leading to secretion of IL-12 and proinflammatory cytokines. If the new vaccine was to be compared to BCG, consideration would also have to be given to the question of withdrawing BCG coverage from part of the trial group, perhaps increasing their risk of potentially fatal childhood tuberculosis. The natural immune response to M. tuberculosis may well have been shaped as much by the evolutionary needs of the microbe as by those of the host.
Key Concept Ranking
- Major Histocompatibility Complex Class II