Adaptive response to intracellular bacteria

To generate a cell-mediated response to intracellular bacteria, cytokines produced by DC (signal 3) polarize naive CD4s to the Th1 phenotype (IL-12 and IFN-γ).

Th1s can super-activate macrophages to promote killing of phagocytosed bacteria. NKs are also important in providing IFN-γ to activate naive CD4s and macrophages.

"Super-activating" macrophages
2 signals for activation: This combination of signals induce changes in gene expression to allow...
 * 1) TCR : MHC II-peptide
 * 2) CD40L : CD40
 * Better fusion of phagosomes with lysosomes
 * Increased production of toxic oxygen radicals (also damaging to healthy tissues)

Granuloma formation
Some intracellular bacteria persist inside macrophages, leading to chronic, low-level infection. An ongoing Th1 response is required to limit proliferation and spread of bacteria, leading to the formation of a granuloma.

In the case of tuberculosis, the centres of granulomas can become necrotic. Cells in the centre begin to die due to noxious stimuli, including toxic products of activated macrophages.

Macrophages attempt to wall off substances that they are not able to eliminate. These macrophages may be surrounded by Th cells.