| While only 10% of TB infection progresses to TB disease, if untreated the death rate is 51%. TB infection begins when MTB bacilli reach the pulmonary alveoli, infecting alveolar macrophages, where the mycobacteria replicate exponentially. The primary site of infection in the lungs is called the Ghon focus. Bacteria are picked up by dendritic cells, which can transport the bacilli to local (mediastinal) lymph nodes, and then through the bloodstream to the more distant tissues and organs where TB disease could potentially develop: lung apices, peripheral lymph nodes, kidneys, brain, and bone.
Tuberculosis is classed as one of the granulomatous inflammatory conditions. Macrophages, T lymphocytes, B lymphocytes and fibroblasts are among the cells that aggregate to form a granuloma, with lymphocytes surrounding infected macrophages. The granuloma functions not only to prevent dissemination of the mycobacteria, but also provides a local environment for communication of cells of the immune system. Within the granuloma, T lymphocytes (CD4+) secrete a cytokine such as interferon gamma, which activates macrophages to destroy the bacteria with which they are infected, making them better able to fight infection. T lymphocytes (CD8+) can also directly kill infected cells.
Importantly, bacteria are not eliminated with the granuloma, but can become dormant, resulting in a latent infection. Latent infection can be diagnosed only by tuberculin skin test, which yields a delayed hypersensitivity type response to purified protein derivatives of M. tuberculosis in an infected person.
Another feature of the granulomas of human tuberculosis is the development of cell death, also called necrosis, in the center of tubercles. To the naked eye this has the texture of soft white cheese and was termed caseous necrosis.
If TB bacteria gain entry to the blood stream from an area of tissue damage they spread through the body and set up myriad foci of infection, all appearing as tiny white tubercles in the tissues. This is called miliary tuberculosis and has a high case fatality.
In many patients the infection waxes and wanes. Tissue destruction and necrosis are balanced by healing and fibrosis. Affected tissue is replaced by scarring and cavities filled with cheese-like white necrotic material. During active disease, some of these cavities are in continuity with the air passages bronchi. This material may therefore be coughed up. It contains living bacteria and can pass on infection.
Treatment with appropriate antibiotics kills bacteria and allows healing to take place. Affected areas are eventually replaced by scar tissue.
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