Tuberculosis

Tuberculosis spreads through airborne transmission when an infected person releases aerosolized droplet nuclei containing Mycobacterium tuberculosis. These microscopic particles are inhaled by another person and travel to the alveoli in the lungs, where infection begins. The bacteria's lipid-rich cell wall allows it to resist destruction and survive within alveolar macrophages.

Alveolar macrophages engulf the bacteria but cannot destroy them due to the pathogen's specialized lipid-rich cell wall. Additionally, cord factor, a glycolipid virulence factor on the bacterial surface, promotes bacterial aggregation into serpentine cords that evade effective immune clearance. This allows the bacteria to survive and persist within the phagocytes.

A granuloma is an organized structure composed of macrophages, epithelioid cells, and T lymphocytes that walls off infected bacteria. It forms when immune cells surround the infection site in response to bacterial multiplication and inflammation in lung tissue. Inside the granuloma, most bacteria remain dormant, establishing a clinically asymptomatic, noninfectious latent state.

Latent tuberculosis reactivates when immunity weakens due to malnutrition, advanced age, or co-infections like HIV. In older individuals, reduced T-cell production from thymic shrinkage weakens immune defense. In malnourished individuals, low white blood cell counts reduce infection control. When granulomas break down, bacteria rapidly multiply, causing active symptomatic tuberculosis with persistent cough and tissue damage.

Infected macrophages traverse the alveolar epithelium, disseminating Mycobacterium tuberculosis into surrounding lung tissue and regional lymph nodes. As bacteria multiply inside macrophages, some cells die and release bacteria into lung tissue, triggering an inflammatory response. This recruitment of immune cells to the infection site ultimately leads to granuloma formation.

Latent tuberculosis occurs when bacteria remain dormant within granulomas, causing no symptoms and no transmission risk. Active tuberculosis develops when granulomas break down, allowing rapid bacterial multiplication, inflammation, and tissue damage. Active disease produces symptoms like persistent cough and releases infectious droplets into the air, making it contagious.

Cord factor, a glycolipid on the bacterial cell wall, induces formation of serpentine cords through bacterial aggregation. These cords are inefficiently phagocytosed by interstitial macrophages, allowing bacteria to escape immune clearance. This virulence factor enables the pathogen to persist and recruit additional immune cells, ultimately leading to granuloma formation and chronic infection.