TB Manual

At the time of initial infection, the distribution of inhaled droplet nuclei in the lung is determined by the pattern of regional ventilation. It thus tends to follow the most direct path to the periphery and to favor the middle and lower lung zones, which receive most of the ventilation.⁵⁷ In immunocompetent hosts, it is theorized that alveolar macrophages ingest the M. tuberculosis organisms. Whether or not those macrophages destroy the bacteria depends on the degree to which they are nonspecifically activated, on host genetic factors and on resistance mechanisms in the bacteria.⁵⁸ If bacteria are successfully cleared, then immunological tests like the tuberculin skin test (TST) and IGRA will remain negative.

When innate macrophage microbicidal activity is inadequate to destroy the initial few bacteria of the droplet nucleus, they replicate logarithmically, doubling every 24 hours until the macrophage bursts to release its bacterial progeny.⁵⁹ New macrophages attracted to the site engulf these bacilli, and the cycle continues. The bacilli spread from the initial lesion via the lymphatic and/or circulatory systems to other parts of the body. This spread may, in fact, be critical to the induction of cellular immunity (see the following section). It is also during this stage of the infection that seeding of the lung apices occurs, which is so critical to the later development of adult-type (infectious) pulmonary TB.⁵⁹ After a period lasting from 3 to 8 weeks, the host develops specific immunity (cell-mediated immunity and delayed-type hypersensitivity) to the bacilli. This is when individuals first show positive results on the TST or IGRA. M. tuberculosis-specific lymphocytes then migrate to the site of infection, surrounding and activating macrophages localized to the site. As the cellular infiltration continues, the center of the cell mass, or granuloma, becomes caseous and necrotic. Later, radiographically demonstrable fibrocalcific residua of the initial infection can be identified, including a calcified granuloma in the lung alone or in combination with a calcified granulomatous focus in a draining lymph node, called a Ranke complex.⁶⁰ Infection and immune conversion are usually asymptomatic; any symptoms that do occur are self-limited. In a small proportion of those infected, erythema nodosum (a cutaneous immunologic response to an extracutaneous TB infection) or phlyctenular conjunctivitis (a hypersensitivity reaction) may develop.

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