A 63-year-old man comes to the emergency department due to fever and cough. A medical student interviews and examines the patient and notes that he has had 3 months of fevers, night sweats, and productive cough. Chest x-ray reveals a right apical lung lesion, and the patient is subsequently placed in respiratory isolation. The medical student was in close contact with the patient during the initial interview and the patient coughed frequently during their interaction. The student had a negative tuberculin skin test prior to beginning the rotation. If this patient's infectious disease is transmitted to the student, which of the following processes is most likely to occur during the first week after exposure?
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Mycobacterium tuberculosis is a facultative intracellular, acid-fast bacillus that is transmitted via aerosolized droplets. The pathogen is frequently inhaled into the lower lobe of the lung where it replicates within the alveoli. Alveolar macrophages phagocytose the organism but are initially unable to eliminate it due to microbial virulence factors (eg, cord factor) that prevent phagolysosome fusion and acidification. This allows M tuberculosis to replicate in an unchecked fashion within the phagosomes of alveolar macrophages for the first few weeks of the infection.
After a few weeks, antigen-presenting cells in the draining lymphatic system display mycobacterial antigens and release interleukin-12, which stimulates naïve CD4 lymphocytes to differentiate into T helper type 1 (TH1) cells. Th1 cells release interferon-gamma (Choice B), which activates macrophages and causes them to:
Form fully acidified phagolysosomes that are capable of destroying intracellular mycobacteria
Differentiate into epithelioid cells and multinucleated Langhans giant cells that surround extracellular mycobacteria within granulomas (Choice A). These cells release digestive enzymes and generate reactive oxygen species, which helps limit mycobacterial proliferation but also cause caseating necrosis and (in some patients) cavitary lung lesions (Choice E).
(Choice D) Although B lymphocytes form antibodies against M tuberculosis, antibodies play a minimal role in the elimination of facultative intracellular organisms (intracellular bacteria are shielded from immunoglobulins).
Educational objective:
Primary tuberculosis infection is marked by initial unchecked Mycobacterium tuberculosis replication within the alveolar space and alveolar macrophages. After a few weeks, CD4 lymphocytes are stimulated to release interferon-gamma, which activates macrophages and allows them to destroy the mycobacteria.