Tuberculosis (TB) is an infectious disease caused by the bacterium Mycobacterium tuberculosis (Mtb), which is transmitted through the air. Once inhaled, these bacteria begin a complex interaction with the host’s immune system, primarily targeting the pulmonary system. This interaction determines the outcome of the infection and the extent of lung damage. This article details the biological mechanisms by which Mtb establishes itself and affects the structure and function of the lungs.
Initial Entry and Immune Containment
The initial infection begins when aerosolized droplets containing Mtb are inhaled and travel deep into the lung’s air sacs, the alveoli. Here, the bacteria are immediately encountered by alveolar macrophages, the resident immune cells tasked with engulfing and destroying foreign invaders. The macrophage attempts to neutralize the threat by enclosing the bacterium within a phagosome, which normally fuses with a lysosome to form a destructive phagolysosome.
However, Mtb possesses unique mechanisms that subvert this protective process. It actively inhibits the fusion of the phagosome with the lysosome, neutralizing the macrophage’s primary killing mechanism. This allows the bacteria to survive and replicate inside the alveolar macrophage, using the host cell as a protected niche. Infected macrophages then release signals that recruit other immune cells, including T-lymphocytes and more macrophages, to the site of infection.
This recruitment and aggregation of cells form a dense, organized structure known as a granuloma, or tubercle. The granuloma is a walled-off cluster of immune cells surrounding the infected macrophages, isolating the bacteria from the rest of the lung tissue. When successful, this containment results in latent TB infection, where the bacteria are alive but dormant and suppressed by the cellular structure.
The Mechanism of Tissue Damage
The transition from latent infection to active TB disease occurs when the immune system fails to maintain the integrity of the granuloma. Factors such as immune suppression or a high bacterial load can lead to the breakdown of the cellular wall. Once the granuloma destabilizes, Mtb bacteria multiply rapidly, initiating a highly destructive inflammatory response in the lung tissue.
The most distinctive form of tissue destruction in active pulmonary TB is caseous necrosis, or “cheesy death.” This process is characterized by the breakdown of tissue into a soft, amorphous, yellowish-white material resembling cheese. This texture results from the death of infected cells and the accumulation of lipids. This necrotic material is non-functional and represents the irreversible destruction of the lung’s parenchyma, the tissue responsible for gas exchange.
As caseous necrosis expands, it often erodes into the lung’s airways, such as the bronchi. This communication allows the semi-liquid necrotic material, densely packed with live Mtb bacteria, to be expelled through coughing. The expulsion creates hollow spaces called cavities, a hallmark of advanced pulmonary disease. Cavities form frequently in the upper lobes, likely due to the higher oxygen concentration in these regions, which promotes the growth of aerobic Mtb bacteria.
The formation of these cavities significantly increases the bacterial load and the risk of transmission. The loss of lung tissue due to necrosis and cavitation severely compromises the lung’s ability to function properly. Furthermore, the bacteria and necrotic debris can spread via the airways from the primary cavity to other parts of the same lung or the opposite lung, leading to a wider spread of localized disease.
Long-Term Structural Changes and Symptom Manifestation
Regardless of treatment, the extensive tissue damage caused by caseous necrosis and cavitation initiates a lasting wound-healing response. The body attempts to repair the destroyed tissue by depositing large amounts of collagen, a process called fibrosis, which leads to permanent scarring. These dense and extensive scars often result in post-tuberculosis lung disease.
In some cases, the necrotic material within the granulomas and cavities undergoes calcification, hardening into a stone-like consistency that leaves a permanent, non-functional residue. This extensive structural remodeling, including thick-walled cavities, fibrotic bands, and calcification, permanently alters the lung architecture. The resulting scarred tissue is less elastic and significantly reduces the functional area available for respiration.
These structural changes directly impair the mechanical efficiency of breathing and the process of gas exchange. The reduced functional lung capacity often leads to chronic respiratory symptoms, such as persistent shortness of breath (dyspnea), even after the infection is cured. The presence of cavities and damaged airways can also lead to a chronic cough, as irritation and structural abnormalities persist.
Furthermore, the erosion of tissue into the airways can sometimes involve small blood vessels, leading to hemoptysis, or coughing up blood. The chronic inflammation and structural distortion of the airways can also result in bronchiectasis, a condition where the bronchi become permanently widened and damaged, leading to mucus buildup and increased susceptibility to recurrent respiratory infections.