How does our immune system battle tuberculosis (TB)? This comprehensive review summarizes the current understanding of host defense and pathogenic mechanisms operative in *Mycobacterium tuberculosis* infection. It discusses the roles of macrophages, T cells, and the cytokine/chemokine network in generating protective immunity. The authors focus on the organism's ability to survive within macrophages by controlling phagolysosome fusion. Recent studies on Toll-like receptors and their impact on the innate response to *M. tuberculosis* are discussed. The review also highlights the induction, specificity, and effector functions of CD4+ and CD8+ T cells, as well as the roles of cytokines and chemokines in shaping the immune response. The presentation of mycobacterial antigens by MHC class I, class II, and CD1 molecules is discussed, emphasizing the implications of these molecules sampling various cellular compartments for presentation to T cells. This review integrates animal models and human studies to provide a greater understanding of tuberculosis and the steps needed to combat this infection. Continued research is essential for realizing an effective vaccine in the coming decades, offering hope for controlling this global health challenge.
Published in the Annual Review of Immunology, this paper squarely fits within the journal's scope. It provides a comprehensive overview of the immunology of tuberculosis, highlighting key aspects of the host immune response. The article aligns with the journal's goal to provide in-depth analyses of timely and significant topics in immunology.