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Infection 'alarm' yields clues to immune system behavior

ry a message about this health threat to neighboring blood vessel cells, asking them to join in the fight. To send this message, a TNF molecule latches onto the surface of a neighboring cell and accesses a biological information highway called the NF-kappaB pathway. Via a series of chemical reactions that act like signals traveling over a telephone wire, TNF's message moves along this pathway from the cell's surface to its nucleus.

At the end of this pathway, NF-kappaB molecules are released to carry the alarm into the nucleus, the cell's control center. Inside the nucleus, the NF-kappaB molecules switch on genes that produce infection-fighting proteins. These proteins launch several strategies to fight the microscopic invaders, such as sending more white blood cells to engulf the bacteria or toxins. The proteins also set off a response known as inflammation, characterized by redness, swelling and pain.

In their journal article, Levchenko and his colleagues reported several important new discoveries about this cellular signaling system. "You could think of the TNF molecule, which sounds the alarm, as a very weak radio transmitter. It moves very slowly as it carries its warning message to neighboring cells, so it is unable to send that message over long distances," Levchenko said. "However, we discovered that the cellular pathways that pick up this signal act like extremely sensitive radio receivers. They can pick up the alarm message from exposure to even a very small amount of TNF. This turns out to be a very smart strategy on the part of the cells."

He explained that a pricked finger usually generates a very localized fight against infection, involving only nearby cells. If TNF's signal was strong enough to set off an immune response involving the entire body, the result could be a high fever and septic shock. "We've developed a better understanding of why the fight against a local infection stays local," said Raymond Cheong, a graduate stu
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Source:Johns Hopkins University


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