Summary Immune responses following infection by pathogenic mycobacterial species involve the physiopathological mechanisms of the disease, the mechanisms leading to healing and to acquired protection and some with the potential ability to be used as individual or epidemiological diagnostic tools. The knowledge of such mechanisms might help to understand the clinical and histological expressions of the different forms of the disease, that occur after the primary infection, some of them being involved with the healing mechanisms. Mycobacterial diseases are chronic infections in which the major pathological expression involves the formation of immune granulomas. Such granuloma are the results of multiple cellular interactions, induced by locally released cytokines, made by pro-inflammatory helper CD 4. The degree and size of the inflammatory reaction might be due to mycobacterial factors (route of inoculation, inoculum size, and virulence) and to host factors (able or not to suppress the inflammation and immune responses). The specific acquired protection seems to be mediated by an other T cell mechanisms, being able to limit quite rapidly and effectivly the secondary mycobacterial inoculum. The cells responsible for such acquired resistance (being demonstrated in mice) are the memory T 4 lymphocytes being resistant to cyclophosphamide. Opportunistic mycobacterial infections in the normal host are usually self limited and can only by detected by the use of immune skin tests reactions. Under special conditions, and in general following alteration of the immune defense mechanisms, involving CD 4+ lymphocytes, two different clinical observations can be made. The first one might be associated with the increased frequency of the typical or subtypical expression of the disease in a particular population as compared to control population. Such frequency might be linked with a decline or absence to induce CD 4+ memory T cell in such individuals. The inflammatory CD 4 inflammatory T cell being still functionnal. The second situation might be due to a more profond defect of all the CD 4+ T cell population, and the disease is then characterized with disseminated, lepromatous-like lesions, present in various organs without inflammatory reaction. Only a limited numbers of opportunistic mycobacterial species and strains are isolated in such patients, which can be explained by their higher residual virulence, enable then to survive inside macrophages. The immuno-selective approaches of the lymphocytes subpopulations, the characteristics of the bio reactive cytokine network and the detection of the specific inducer molecules will allow us to understand the nature and mechanisms of the development and healing of the lesions and might help us to find new ways to treat such infected immunocompromised patients by using immunological interventions associated with efficient chemotherapy.