Abstract Intracellular pathogens whether facultative like Mycobacterium sp., e.g. Bacillus Calmette Guérin, Listeria monocytogenes or strictly intracellular like Leishmania sp. initiate either asymptomatic infectious processes or disease depending both on factors of the host (genetic as well as environmental ones) and the infectious/pathogenic agents. In this contribution, we first summarized informations which justify to develop in situ analysis to decipher the sequential events that result in different modes/classes of immune responses. How the mode of the immune response is determined remains a main question to address. Although it has recently become clear, in vitro, that immunocompetent cells and their cytokines are critical to set on a stable mode of immune response, acting on naive T cells, this area deserves more in vivo studies. Indeed, peripheral T cells, at different stages of differentiation, may exist in vivo (a) naive/virgin, (b) experienced, (c) effector T cells, depending on the level of stimulation of the immune system by either endogenous or exogenous (e. g. gut flora) signals. The three chosen examples illustrate our contributions in this field focusing on three different non-lymphoid tissues which may become infected: bone marrow (Bacille de Calmette Guerin), liver ( Listeria monocytogenes), skin ( Leishmania major). These three illustrations also allow to attract attention on the interest of using mice of genetically different strains the immune response of which is set up under different modes.