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Mycobacterium tuberculosis

Pathogenesis


          Infection with Mycobacterium tuberculosis begins when droplet nuclei are inhaled into the upper respiratory tract through the mouth or the nose (Figure 2, box 1).  From the upper respiratory tract, the bacilli travel through the bronchi until they reach the alveoli of the lungs (Figure 2, box 2).  Once inside the lungs, alveolar macrophages (immune cells that engulf foreign particles) ingest the pathogenic organisms, but the mycobacteria do not die.  Instead, the bacilli multiply within the macrophage hosts, causing the macrophages to rupture.  The continued division of M. tuberculosis every 18 to 24 hours attracts more and more immune cells to the area.  In an attempt to control the infection, some of these cells produce toxic substances that are supposed to kill the bacilli.  The bacilli do not immediately die, however, so the release of toxic substances also damages the surrounding lung tissue.  When macrophages and other cells of the immune system encircle this area of dead tissue, the lesion is called a tubercle or granuloma (Figure 1).
 

Centers for Disease Control and Prevention. http://phil.cdc.gov/phil/quicksearch.asp

Figure 1.  Mycobacterium tuberculosis bacilli visible within granuloma.  This tissue sample was taken from the endometrial layer of the uterus.  This is an example of tuberculosis disease persisting in an area of the body outside of the lungs.
 
          The interior of a tubercle consists of a gelatinous mass of host cells and bacilli that gives the damaged tissue a cheese-like consistency.  Therefore, this type of tissue death is referred to as caseation necrosis.  If the immune system is successful in preventing the M. tuberculosis bacilli from multiplying further, the caseous tubercles become walled-off and calcified (Figure 2, box 4).  Although calcified lesions still contain viable bacteria, the bacteria cannot be spread to other individuals.  When Mycobacterium tuberculosis lies dormant in the lungs, a person is said to have a latent tuberculosis infection.  Such persons, who represent 85-95% of infected individuals, show no overt symptoms of disease.
 
          In 5-15% of infected individuals, the immune system fails to prevent the infection from progressing and the interiors of the caseous lesions become liquefied.  Liquefaction allows viable M. tuberculosis bacilli to spill out of the tubercles, leaving behind a cavity in the lungs (Figure 2, box 5).  When these bacilli infect lower portions of the lungs or enter the bronchi the result is an active case of pulmonary tuberculosis disease.  People with pulmonary tuberculosis are capable of spreading the disease to others through the bacteria in their sputum.  They also manifest symptoms such as weight loss, weakness, night sweats, chest pain, and coughing up blood.  If viable bacilli enter the bloodstream, M. tuberculosis can travel to organs of the body outside of the lungs (Figure 1, above and Figure 2, box 3).  Known as extra-pulmonary tuberculosis, this form of the disease is rarely contagious.
 
Centers for Disease Control and Prevention. http://www.phppo.cdc.gov/phtn/tbmodules/modules1-5/m1/con6a.htm

Centers for Disease Control and Prevention. http://www.phppo.cdc.gov/phtn/tbmodules/modules1-5/m1/con6a.htm

Centers for Disease Control and Prevention. http://www.phppo.cdc.gov/phtn/tbmodules/modules1-5/m1/con6a.htm

Centers for Disease Control and Prevention. http://www.phppo.cdc.gov/phtn/tbmodules/modules1-5/m1/con6a.htm

Centers for Disease Control and Prevention. http://www.phppo.cdc.gov/phtn/tbmodules/modules1-5/m1/con6a.htm


Figure 2. 
Diagram depicting the pathogenesis of infection with Mycobacterium tuberculosis.

 

         
          As mentioned earlier, people with latent tuberculosis infection retain viable M. tuberculosis bacilli within their lungs, even though they are asymptomatic and not infectious.  When a person with latent TB becomes immunosuppressed because of old age, lifestyle choices, illness, or a medical condition such as HIV, the dormant bacteria can reactivate within the calcified tubercles.  Thus, people with latent tuberculosis infection always run the risk of developing active TB disease.