Tuberculosis (TB) is primarily a lung disease, and its dissemination depends on the successful infection of this critical organ. Upon aerosol infection with *Mycobacterium tuberculosis* (Mtb), the acquired cellular immune response is slow to be induced and expressed within the lung, allowing the infection to establish and forcing the response to be expressed in an inflammatory site modulated by the bacterium. Mtb interacts with the innate immune response through various surface molecules, leading to suboptimal control of bacterial growth. To improve current vaccine strategies, it is essential to understand the factors that mediate the induction, expression, and regulation of the immune response in the lung, as well as how to induce both known and novel immunoprotective responses without causing immunopathologic consequences. The pathogenesis of TB involves the interaction between bacterial virulence and host resistance. The key to understanding this interaction lies in the role of lymphocytes, particularly CD4 T cells, in mediating both protective immunity and immunopathologic consequences. The rapidity of the acquired cellular response is crucial, as a slow response allows bacteria to grow and reach levels where protective immunity is ineffective. The dose of infection also plays a role, as high doses can interfere with the efficient expression of protective immunity. Recent studies have focused on the initiation and development of cellular responses, the role of different T cell subsets, and the impact of phagocytes on bacterial control. Dendritic cells are key inducers of naive T cell activation, but their function can be altered by Mtb. The development of effector T cell subtypes, such as multifunctional and cytolytic CD4 T cells, has been identified, and their protective role is being explored. Phagocytes, particularly macrophages, also play a crucial role in controlling Mtb, and their functions, such as autophagy and vitamin D-dependent antimicrobial activity, are being investigated. The role of pattern recognition receptors, including TLRs and C-type lectins, in modulating the immune response to Mtb is another area of focus. The phenotypic complexity of phagocytic mononuclear cells in the infected lung and the potential impact of regulatory T cells and IL-10 on the immune response are also discussed. Overall, the understanding of the complex interactions between Mtb and the host immune system is essential for developing effective vaccines and treatments for TB.Tuberculosis (TB) is primarily a lung disease, and its dissemination depends on the successful infection of this critical organ. Upon aerosol infection with *Mycobacterium tuberculosis* (Mtb), the acquired cellular immune response is slow to be induced and expressed within the lung, allowing the infection to establish and forcing the response to be expressed in an inflammatory site modulated by the bacterium. Mtb interacts with the innate immune response through various surface molecules, leading to suboptimal control of bacterial growth. To improve current vaccine strategies, it is essential to understand the factors that mediate the induction, expression, and regulation of the immune response in the lung, as well as how to induce both known and novel immunoprotective responses without causing immunopathologic consequences. The pathogenesis of TB involves the interaction between bacterial virulence and host resistance. The key to understanding this interaction lies in the role of lymphocytes, particularly CD4 T cells, in mediating both protective immunity and immunopathologic consequences. The rapidity of the acquired cellular response is crucial, as a slow response allows bacteria to grow and reach levels where protective immunity is ineffective. The dose of infection also plays a role, as high doses can interfere with the efficient expression of protective immunity. Recent studies have focused on the initiation and development of cellular responses, the role of different T cell subsets, and the impact of phagocytes on bacterial control. Dendritic cells are key inducers of naive T cell activation, but their function can be altered by Mtb. The development of effector T cell subtypes, such as multifunctional and cytolytic CD4 T cells, has been identified, and their protective role is being explored. Phagocytes, particularly macrophages, also play a crucial role in controlling Mtb, and their functions, such as autophagy and vitamin D-dependent antimicrobial activity, are being investigated. The role of pattern recognition receptors, including TLRs and C-type lectins, in modulating the immune response to Mtb is another area of focus. The phenotypic complexity of phagocytic mononuclear cells in the infected lung and the potential impact of regulatory T cells and IL-10 on the immune response are also discussed. Overall, the understanding of the complex interactions between Mtb and the host immune system is essential for developing effective vaccines and treatments for TB.