ABSTRACT
The outcome of infection by Mycobacterium tuberculosis is crucially dependent on the immune response of the host. Most infected individuals mount a response that is sufficient to prevent progression to disease but allow persistence of viable bacteria in the form of a latent infection. Ten percent of infected individuals develop clinical tuberculosis (TB) during their life, either as a result of failure to control the initial infection or due to reinfection or reactivation of latent infection (1). In immunocompromised individuals, the risk of developing tuberculosis increases to 5% to 10% annually. The development of secondary disease due to reinfection or reactivation of latent infection highlights a major challenge for TB vaccines. The hallmark of the adaptive immune system is its ability to learn froman initial infection how tomount a rapid and effective responsewhen re-exposed to the same pathogen. Classically, vaccinationmimics the learning process associatedwith natural infection. Development of a secondary disease in individuals who had contained a primary infection with M. tuberculosis shows that the robust learning process seen for a disease like smallpox does not always occur for TB (1). Similarly, individuals who have been cured of TB remain susceptible to reinfection and further disease (2).
