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Infection 'alarm' yields clues to immune system behavior

Drawing on lab experiments and computer studies, Johns Hopkins researchers have learned how a common protein delivers its warning message to cells when an infectious agent invades the body. The findings are important because this biological intruder alarm causes the body's immune system to leap into action to fight the infection. Learning more about how this process works, the researchers said, could lead to better treatments for diseases that occur when the immune system overreacts or pays too little attention to the infection alarm.

Collaborating with colleagues at the University of California, San Diego, the Johns Hopkins researchers have used their discoveries to develop a new computer model that could help produce medications for immune system-related ailments including septic shock, cancer, lupus and rheumatoid arthritis.

Their findings, which focused on how a large protein molecule called tumor necrosis factor, or TNF, triggers an immune response, were reported in the February issue of the Journal of Biological Chemistry.

"We were surprised by how sensitive cells were to small amounts and brief exposures to TNF," said Andre Levchenko, a Johns Hopkins assistant professor of biomedical engineering and senior author of the paper. "Our analysis may help drug companies solve problems with the regulation of immune response levels, and do it in a smart way."

In particular, Levchenko's team looked at the innate immune response, a localized reaction which normally stops an infection threat confined to a small part of the body, such as in the case of a pricked finger. (This is in contrast to a systemic response that triggers an immune reaction throughout the body, causing a fever. If the immune system responds too aggressively in such cases, the result may be a dangerous condition called septic shock.)

The innate immune response begins when white blood cells detect a bacterial intruder or toxin in the body. They produce TNF to car
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Source:Johns Hopkins University


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