Pathophysiology of Tuberculosis: Mechanisms and Implications

You inhale TB bacteria and your lungs try to wall them off — sometimes successfully, sometimes not. When someone with active TB coughs, tiny droplets containing Mycobacterium tuberculosis float in the air. If you breathe them in, the bacteria reach the small air sacs in your lungs. Immune cells called alveolar macrophages swallow the bacteria and try to destroy them. In most people the immune system succeeds in containing the infection inside a small clump of cells called a granuloma — the bacteria are trapped but not always killed. This is latent TB: no symptoms, not contagious. In about 5–10% of infected people, the granulomas fail and bacteria multiply, causing active TB with cough, fever, weight loss and night sweats.

A granuloma is the immune system's cage around TB bacteria — it stops the infection from spreading but rarely eliminates it. Structurally, a granuloma is a ball of infected macrophages at the centre, surrounded by T-cells and fibrous tissue on the outside. Its job is containment, not cure. As long as the granuloma stays intact, the person has latent TB and cannot infect others. If the immune system weakens — due to HIV, diabetes, malnutrition, cancer treatment or older age — the granuloma can break down, releasing bacteria into the airways. That is what turns latent TB into active, contagious disease. This is why TB can appear years or even decades after the original infection.

Latent TB means the bacteria are asleep; active TB means they are multiplying and causing illness. In latent TB the person has no symptoms, cannot spread the infection to others, and usually has a positive tuberculin skin test or IGRA blood test but a normal chest X-ray. Around one in four people globally carry latent TB. Active TB shows up as persistent cough (often more than two weeks), weight loss, low-grade fever, night sweats and sometimes blood in sputum. Active TB is contagious and needs at least six months of combination antibiotics — usually isoniazid, rifampicin, ethambutol and pyrazinamide. Latent TB may also be treated preventively in high-risk people (HIV, close contacts, immunosuppression) to stop it from ever becoming active.

Anything that weakens the immune system can flip TB from latent to active. The strongest triggers are HIV infection (which raises lifetime reactivation risk from around 10% to more than 50%), uncontrolled diabetes, chronic kidney disease, long-term steroid or biologic therapy, cancer chemotherapy, malnutrition and heavy smoking or alcohol use. Ageing and pregnancy also raise the risk modestly. Silica dust exposure (mining, stone-cutting) is a well-known occupational trigger. If someone with known latent TB develops a persistent cough, unexplained weight loss or repeated evening fever, they should get a sputum test and chest X-ray without delay — early treatment prevents spread and organ damage.