Figure 1.

A. A schematic illustration of the potential outcomes on infection with Mtb. In most hosts Mtb exhibits rapid expansion of the bacterial burden over the first 3–4 weeks of infection. At this point the acquired immune response has developed and controls the bacterial burden at a subclinical level but is unable to clear the infection. In vaccinated hosts this transition to control of the bacterial burden is achieved at around a log fewer bacilli. While resolution of infection is possible theoretically it is virtually impossible to demonstrate. Progression from latent disease to active disease appears to occur in the face of a robust systemic immune response that is Th1 dominant. While there are candidate indicators of early disease progression the field lacks immunological markers to detect vaccine-induced protection. Published previously in (10). B. The main features of the human TB granuloma. A fully-formed human TB granuloma is an extremely stratified structure. The center of the granuloma is caseous in nature and rich in lipids, thought to be derived from the lipids present in foamy macrophages. The caseum is surrounded by a macrophage-rich layer that contains foamy macrophages, multi-nucleate giant cells and epithelioid macrophages. Mtb bacilli are observed in many of these cells. This structure is frequently encased in a fibrous capsule of collagen and other extracellular matrix proteins. Lymphocytes tend to be restricted to the periphery of the granuloma outside the fibrous outer layer. Published previously in (77).