In each new engagement, a fresh set of immune recruits must size up the enemy and choose the right plan of attack. But if for any reason they falter in the line of duty--the environment grows toxic, say, or scrambles bio-chemical orders meant for the recruits--the results can be disastrous, ranging from the self-destructive "friendly fire" of autoimmune disease to illness or death from infections or tumors.
Laurie Glimcher, the Irene Heinz Given Professor of Immunology, and her colleagues at the Harvard School of Public Health are interested in preventing these sorts of catastrophes. By illuminating the molecular chain of command used by helper T cells, the field commanders of the immune battle, Glimcher hopes to combat diseases like arthritis, allergies, and atherosclerosis.
To get a look at the events that normally send T cells down one path or the other, Glimcher and research fellow Roberto Maldonado used video microscopy to peer inside the immunological synapse just as T cells and dendritic cells united. Using colored tags to follow a variety of messenger molecules as they moved around on the T cells' surface, the scientists discovered that T cells destined for TH1 status summoned one particular group of molecules into the synapse, while T cells bound for the TH2 pathway called forth a different set.
But what happens when this signaling goes awry, as in disease states, upsetting the balance of TH1 and TH2? TH1 cells are essential for fighting off infections and tumors, but too many TH1s can lead to excessive inflammation, the underlying cause of diseases from arthritis to atherosclerosis. When TH2 cells proliferate or become hyperactive, allergies and asthma may result.
for new therapies
The immune system could face its ultimate test in a war waged with bioterrorist agents like anthrax or smallpox. But Glimcher hopes to cover even that scenario one day. In 2003, her lab received $20 million from the National Institute of Allergy and Infectious Diseases to find ways of bolstering immune defenses against pathogens both familiar and new.
Pat McCaffrey is a freelance journalist who writes about biology and medicine.
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