After the pathogen has been eliminated, most of the T lymphocytes die, but a small population continues to circulate throughout the body. These cells are known as memory T lymphocytes, and will be poised and ready should the pathogen appear again. The most effective vaccines induce the immune system to produce memory T lymphocytes, which are crucial to establishing life-long immunity.

Of course, pathogens have tricks to evade the immune system. M. tuberculosis lives in the lungs, in immune cells called macrophages. A weapon in TBs arsenal is an enzyme called superoxide dismutase A, or sodA. This enzyme helps TB cover its tracks, so the macrophage doesnt know its infected. Jacobs and his team hypothesized that eliminating this enzymes activity would give macrophages the opportunity to trigger apoptosis, thus prompting a more effective immune response.

So the researchers deleted the gene responsible for shuttling sodA out of the bacterium, effectively disabling sodA activity. When they compared this mutant strain to normal TB, they saw that it did in fact cause increased apoptosis in macrophages grown in culture.

To get a better picture of what was going on, Jacobs and his team used a mouse that had been genetically altered to have all of its T lymphocytes recognize the same peptide. They altered the normal and the apoptosis-inducing strains of TB to produce this peptide.

The researchers transferred thousands of immune cells from the genetically-altered mice into normal mice, which they then infected with the two strains of TB. This procedure gives scientists a magnified view of the immune systems response. Although both strains of TB produce the same amount of peptide, Jacobs expected infection with the apoptosis-inducing strain to elicit a more dramatic immune response.

The rese
'"/>

Contact: Jennifer Michalowski
michalow@hhmi.org
301-215-8576
Howard Hughes Medical Institute
1-Aug-2007