Causes

Primary Infection

Tuberculosis (TB) is usually caused by Mycobacterium tuberculosis bacteria; it spreads when a person inhales droplets containing the bacteria which have been sneezed out by an infected person. Because Mycobacterium tuberculosis is a small, relatively slow-growing bacterium, it moves only very slowly through the respiratory tract and generally does not cause any symptoms at this stage. Once the bacteria has reached the lungs, however, it takes only an hour for it to reach the draining lymph nodes at the hilum of the lung and some bacteria may escape into the bloodstream.

Components of the mycobacterial cell wall including phenolic glycolipid, lipoproteins, lipoarabinomannan, and phosphatidylinositol mannosides have immunomodulatory effects and are recognised by Toll-like and other innate receptors on dendritic cells and macrophages. Consequently, when the bacteria are ingested by alveolar macrophages, they continue to proliferate. The macrophages release cytokines and chemokines which attract monocytes, neutrophil granulocytes and other inflammatory cells. Macrophages also present the antigen to T lymphocytes, helping to generate cellular immunity. The combination of these factors causes a type IV (delayed type) hypersensitivity reaction to the organism which is able to control 95% of infections after a primary infection. However, the ability of the bacteria to proliferate inside naive macrophages, lyse the host cell and infect other macrophages allows it to disseminate further through the body via the blood.

After a few weeks, T cell-mediated immunity to the bacteria is better developed. Certain T cells may then activate macrophages to kill intracellular mycobacteria in a process associated with the formation of epithelioid cell granulomas. Other T cells are able to lyse infected macrophages and kill mycobacteria and still more T cells are able to lyse macrophages but without killing the mycobacteria. The caseating granulomas characteristic of TB are a result of the lysis and necrosis of infected macrophages, and are thought to provide an acidic, oxygen poor, extracellular environment in which the mycobacteria are unable to proliferate. These caseated regions subsequently form a calcified scar.

"Mycobacterium tuberculosis" image courtesy of Wikimedia Commons under creative commons license: Original image

Secondary Infection and Disseminated TB

 Mycobacteria laying dormant in an infected person may be reactivated or a person could be re-infected either due to enhanced susceptibility on the part of the patient or the emergence of a particularly virulent strain. In such circumstances, new granulomas will form via the same mechanism (delayed type hypersensitivity), often in the apex of the lung but infection may spread to the kidneys, meninges, liver and other organs. In this case, the granulomas fail to contain the mycobacteria, so that widespread caseous necrosis and cavitation may occur.

"Tuberculous Caseous Granuloma" image courtesy of Wikimedia Commons under GNU Free Document License: Original Image

Susceptibility to TB is increased by the following risk factors:

• Close contact with infected people
• Travelling to, receiving visitors from or living in places where TB is very common
• Being immunocompromised by HIV, other medical problems or immunosuppressants
• Being very old or very young, since these age groups have weaker immune systems
• Long term poor health and bad diet due to lifestyle problems like drug abuse, homelessness or alcoholism
• Living in poor or crowded accommodation like prisons or hostels