When the mycobacteria reach the pulmonary alveoli, TB infection begins. The bacteria start invading and replicating within endosomes of alveolar macrophages. Macrophages analyse the bacterium as foreign and try to eliminate the bacteria by phagocytosis. During this process, the mycobacterium is surrounded by the macrophage and placed impermanently in a membrane-bound vesicle called phagosome. The phagosome then associates with lysosome to form phagolysosome. In the phagolysosome, the cell intends to use acid and reactive oxygen species to kill the bacterium. However, M. tuberculosis has a broad, waxy coating of mycolic acid that protects the cell from these toxic substances. M. tuberculosis has the ability to multiply and reproduce inside the macrophage until they burst the macrophage and will finally kill the immune cell, which leads to further infection.
The primary site of infection in lungs, is known as the "Ghon focus", is either located in the lower part of the upper lobe or in the upper part of the lower lobe. Infection through the blood stream may also cause, tuberculosis of the lungs. This is known as Simon focus and is generally found in the upper part of the lungs. The hematogenous transmission may also spread infection to other sites, such as the brain, kidneys, peripheral lymph nodes, and to the bones. Other parts of the body may also be affected by the disease, it may rarely affect the pancreas, heart, thyroid or skeletal muscles.