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Jewish World Review April 4, 2001 / 11 Nissan, 5761

Lee Bowman

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New discoveries about immune cells -- THE immune system takes a long time to forget, but it appears to remember the most vigorous viral attacks longer than it does more frequent but less powerful challenges, according to researchers.

New discoveries about how the memory of immune cells is established are helping researchers develop new vaccines for complex and persistent diseases like HIV, malaria and tuberculosis, said Rafi Ahmed, director of the Emory University Vaccine Center in Atlanta.

When immune system attack cells are exposed to protein switches like those found on the surface of a virus, they divide into two groups: most attack the invaders, and are later themselves destroyed by other immune system cells. But about 5 percent to 10 percent of the cells become memory cells.

They recall the signal of the original virus and lead an even stronger charge against it the next time it shows up in the body.

Ahmed, speaking to a conference on experimental biology Tuesday in Orlando, Fla., said it had long been thought that memory cells need reminders, so that for a vaccine to be most effective, it had to refresh the memory of the immune cells by exposing them repeatedly to the viral proteins.

"Now, we're seriously questioning that hypothesis," Ahmed said.

Instead, he and his colleagues believe recent studies by their team and others show that the key to immune memory is a process called "antigen-driven expansion" during which naive immune cells are activated and undergo a 50,000- to 100,000-fold increase. The effectiveness of long-term immune response depends on the size of this initial expansion.

"This means that in vaccine development the initial stimulant is a critical component of the effectiveness of the vaccine," Ahmed said.

Memory immune cells don't show signs of aging as do most other cells and may even outlive their hosts, apparently by stimulating a key enzyme that regulates aging damage in the genes.

Researchers also know that the pool of total memory cells is maintained at a stable number by the slow proliferation of the memory cells coupled with a slow death rate of other cells. This rate stays the same without the need for repeated exposure to a disease or vaccination.

Other research published late last year by John Harty of the University of Iowa suggests that several molecules already known to take part in battling infections also regulate the size and nature of the initial immune response and the immune memory.

Harty said one substance, called interferon gamma, acts to eliminate most of the activated immune response cells after an infection has been licked. He noted that such cell death is important "because it allows us to respond to many different pathogens without exhausting our immune system.''
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