One of the unique features characterizing human tuberculosis (TB) is its pathogenesis. The pathogenesis of TB involves cell-mediated immune responses against Mycobacterium tuberculosis. Concisely, macrophages activated by various soluble mediators or cytokines released through the cellular interactions after infection with M. tuberculosis play a pivotal role in the pathogenesis of human TB. In fact, very complex cellular interactions are going on within the host after infection with or endogenous reactivation of M. tuberculosis. Cells communicate by cell-cell contact and by the release of mediators which may originate locally, called cytokines.
In TB infection, macrophages can be activated by two ways directly with mycobac terial organisms or lipid fractions of their cell walls at the earlier phase of infection, and indirectly with cytokines produced by CD4⁺ T cells specifically activated by mycobacterial peptide antigens at the later phase of infection. The various clinical features of TB are the summarized outcome of cell to cell interactions mediated by diverse cytokines produced by various immune cells which are initially triggered by M. tuberculosis infection.
CD4⁺ T cells can be classified into two subsets according to the patterns of cytokines they produce Thl cells give rise to cell-mediated immunity and are characterized by the production of IL-2 and IFN-γ, whereas Th2 cells are more efficient in mediating antibody production and secrete IL-4, IL-5, IL-6 and IL-10. Th2 cells can control Thl cells and vice versa. Th2 cells therefore inhibit the production of cytokines by Thl cells by releasing IL-4 and IL-10.
Infection with mycobacteria stimulates macrophage IL-12 production which appears to act directly on naive CD4+ T cells to induce Thl development and initiation of cell-mediated immunity. IL-12 is a critical component in the development of cell-mediated immunity. In addition, IL-12 also activates NK cells and γ/δ T cells, both of which secrete various macrophage-activating factors to kill M. tuberculosis.
One of the structural characteristics of M. tuberculosis is the cell wall rich in lipid components. Of importance among various biological activities of the cell wall lipids is the stimulation of mononuclear phagocytes to produce a certain number of cytokines or monokines including IL-12 and IL-10, both of.which play important roles in regulation of immune responses in mycobacterial infection and in pathogenesis of TB. Considering the biological characteristics of mycobacterial lipid components, we need take these lipids into consideration in the future research of TB immunology, particularly in the strategy for development of a potent TB vaccine