Review Question - QID 100814

Of the above steps, bacterium-mediated inhibition of phagosome-lysosome fusion occurs first in the formation of a granuloma.

It is believed that the M. tuberculosis bacterium is able to interfere with pathways necessary for phagolysosomal formation. By inhibiting the formation of a phagolysosome, the M. tuberculosis is able to proliferate inside of macrophages. However, when the adaptive immune system becomes activated (weeks later), Th1 cells activate macrophages, enabling macrophages to destroy the bacterium and to form epithelioid cells. Fusion of epithelioid cells results in the formation of multinucleated giant cells.

Potter et al. note that despite the falling incidence of M tuberculosis cases, it is still a concern, especially among high risk populations like the homeless and immunocompromised. They recommend treatment with 4-drug therapy initially with isoniazid, rifampin, pyrazinamide, and ethambutol for eight weeks, followed by 18 weeks of isoniazid and rifampin.

Vergne et al. discuss how M. tuberculosis infection and inactivation of macrophage phagolysosome maturation helps the bacterium survive and spread. This is achieved by analagous molecules produced by M. tuberculosis interfering with recruitment and function of rabs, phosphatidylinositol 3-kinases, tethering molecules, calcium and calmodulin signaling and SNAREs.

Image A shows a typical granuloma often seen in an M. tuberculosis infections. Note the high presence of leukocytes and multinucleated giant cells.
Illustration A shows the process leading to granuloma formation and depicts the important roles lymphocytes and macrophages play.

Incorrect Answers:
Answer 1, 2, 4, and 5: All of these steps require activation of the adaptive immune system and, therefore, occur weeks after bacterial infection.