Pathogenesis of Tuberculosis (TB) Infection

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The page below is a sample from the LabCE course Tracking Antibiotic-Resistant Tuberculosis. Access the complete course and earn ASCLS P.A.C.E.-approved continuing education credits by subscribing online.

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Pathogenesis of Tuberculosis (TB) Infection

The cycle of TB infection begins with the dispersion of M. tuberculosis aerosols. Droplets remain airborne for hours, making transmission likely (although dependent on several other factors, such as contact proximity, amount of time spent with contact, and immune status of the contact, to name but a few factors).
  • A dose of 1-10 TB bacilli is contained in a respiratory droplet nucleus.
  • In the patient’s lung, the bacilli are phagocytized by alveolar macrophage cells, which then invade the underlying epithelium.
  • Here, monocytes from nearby blood vessels form the beginning of a granuloma as the immune system attempts to ward off the disease. This is a hallmark characteristic of tuberculosis.
Within the granuloma, a core of infected macrophages is surrounded by foamy macrophages, mononuclear phagocytes, and lymphocytes.
  • The result is a fibrous capsule with increased foamy macrophages, presumed to create the typical caseous debris (necrotic tissue resembling cheese) in the center of the granuloma.
  • Although it appears contained immunologically, the caseous center tends to liquefy and cavitate as it empties thousands of M. tuberculosis bacilli into the airway.
  • The cycle is complete as the damaged lungs produce a cough that contains the highly transmissible infectious droplet nuclei.
Infected macrophages may be carried by the lymphatic system to the lungs, lymph nodes, kidneys, epiphyses of the long bones, and other areas of the body.
  • Infected macrophages may also be carried in the blood of an immunocompromised host (eg, AIDS patient).
  • After 2-8 weeks, despite widespread infection, there are no immediate symptoms or signs other than a positive TB skin test (TST).
  • In children, the elderly, non-white races, and AIDS patients, the disease progresses quickly to pneumonia from hilar or mediastinal lymph nodes to cavitation in the bronchi.
  • It is here that the distribution of caseous material occurs, such as in acute miliary TB (disseminated disease) or TB meningitis, particularly in children.
  • Patients infected at ages over 30 years and less than 65 years have a better prognosis compared to children, adolescents, young adults, and the elderly because they have a lower risk of tissue necrosis.
In general, hypersensitivity develops during the 2-8 week period after infection, signaling the action of cellular immunity and control of the infection.
  • During this time frame, a tuberculin skin test (TST) reaction may be positive indicating latent infection exists. (Interferon gamma-release assays [IGRAs] may also be used in place of TST).
  • In high-risk groups, progression of the disease to cavitation in the lung and hematogenous dissemination are likely to occur.

Progression of the tuberculosis granuloma