Figure 11.

Simulated effects of immune memory on granuloma outcomes. (A) Snapshots of granuloma progression over time with or without memory cells generated from vaccination. When no memory cells are present at the beginning (top row), the site with an initial infected macrophage develops into a granuloma and maintains the structure through the 200 days of simulation. With sufficient memory cells circulating (bottom row), a granuloma appears briefly but quickly resolves as the infection ends in bacterial clearance (sterilization). (B) Infection is simulated with different combinations of initial conditions for each type of memory cell (central, effector, CD4+ and CD8+ T cells). Four groups of simulations are run, each with a fixed low (20 µL⁻¹) or high (100 µL⁻¹) concentration for total CD4+ or CD8+ T memory cells. Within each group, the ratio of central memory (CM) to effector memory (EM) are set to 9:1, 1:1, or 1:9. Each scenario is simulated 50 times, and the outcomes of each granuloma are assessed. Shown in the color are the proportions of simulations that ended in a granuloma that cleared all bacteria. Clearance is defined as less than 500 macrophages and less than 10 replicating M. tuberculosis.