Tuberculosis I: a conceptual frame for the immunopathology of the disease

An analysis of the cellular and humoral immune responses after bacille Calmette-Guerin (BCG) vaccination and during tuberculosis treatment favors the hypothesis of an immune defence developed in four overlapping successive stages. The initial immune response is innate. The following two intermingle innate and specific responses against low molecular weight oligopeptidic and nonpeptidic antigens, as muramyldipeptide and trehalose dimycolate, and large molecular weight nonpeptidic antigens such as lipoarabinomannan. The ultimate specific response is directed against protein antigens as Antigen 60. BCG and primary tuberculosis (TB) infections induce cellular and humoral immune responses essentially against oligopeptidic and small and large molecular weight nonpeptidic antigens. Immune responses against non-peptidic substances contribute to the immunoprotection of the infected person who develops a primary infection. Some infected people allow the expression of the immunosuppressive activity of the pathogen. This results in the synthesis of interleukin-10 (IL-10), which suppresses the formation of interferon-gamma (INF-gamma) and IL-2, and of IL-6, which suppresses T-cell responses. These patients have a skewed immune response against non-peptidic antigens and present with symptoms. They will not recover unless responses directed against proteinic antigens occur, which restore INF-gamma and IL-2 production. The formation of immumoglobulin-G (IgG)-type antibodies and of a cellular immunity against mycobacterial peptidic antigens is essential for a good protection against a post-primary infection.