The Flu Sheds Light on Holes in Immune System Knowledge

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The Flu Sheds Light on Holes in Immune System Knowledge

By Harmon | September 12, 2011

MALTA—Coming down with the flu—and slowly recovering from it—might seem straight

forward enough. But a lot of what happens in your body on a molecular level

during the time between initial infection and full recovery is still somewhat of

a mystery to scientists.

An improved capacity to track the course of an influenza infection could not

only help in the development of more effective vaccines to protect against a

much broader range of strains than just a few passing seasonal ones as are now

included in annual flu shots, but it could also bring new understanding of the

immune system as a whole.

We still don't know " what maintains the size of the immune system " and keeps it

in homeostasis, Doherty, of the University of Melbourne's Department of

Microbiology and Immunology, said September 11, at the European Scientific

Working Group on Influenza (ESWI) fourth annual conference in Malta. Among those

who spend their careers studying viruses—and how to fend them off— " it's kind of

like the big bear in the room, " said Doherty, who shared a Nobel Prize in

Physiology or Medicine in 1996 for his earlier work on how the immune system

recognizes viruses.

The outward symptoms of the flu are familiar enough. And even on a systems

level, scientists can predict, to a certain extent, how the immune system is

going to respond to an infection. But, Doherty said, " What we need to get down

to is what is going on at a molecular level in these cells " in the immune system

under attack.

When the body is exposed to a foreign pathogen, the immune system sends out

various lines of defense. One of these first lines, the CD8 T cells, Doherty

explained, are like Roman soldiers, fighting shoulder to shoulder (with short

swords and large shields so as not to get killed themselves) as " lethal,

close-range delivery systems. " And by seeing how these cells act when confronted

with a new invader, researchers are hoping to disarm the enemy far in advance.

Advances in genomics and epigenetics lately have helped research teams follow

individual immune cells, allowing a new view of how the cell populations

maintain their diversity over time, and adding clues to how the immune system as

a whole changes during and after an infection.

As for the flu, good old-fashioned mouse research (in which researchers " prime "

mice with small doses of a strain or two of the flu then later give them a

different strain to see how their immune cells ramp up over the course of the

infection) has supported much of what researchers now understand about how the

body recognizes different strains. Unlike mice who had never been exposed to the

flu, mice that first got small amounts of H1N1 survived an infection of the much

more virulent H7N7 strain, suggesting that their immune systems were ready to

attack even a different form of the virus. But those mice that had gotten both

H1N1 and an H3N2 primer were much more effective in beating back the infection

quickly.

That said, Doherty pointed out, " we're not nice clean organisms like a lab

mouse. " As humans age, he noted, our immune systems are exposed to all sorts of

infections to which our bodies develop specific antigens. And that makes

studying immune responses in humans more complicated.

But research done during the 2009 H1N1 outbreak showed that young children

followed very much the same time course as lab mice, launching an immune

response in about seven days. This finding adds support to the ongoing research

in mice to help develop a better understanding of human immune dynamics.

For now, the flu remains unpredictable. And some strains out there, such as

H5N5, are extremely deadly and don't seem to be daunted by an equipped, primed

immune system. And for strains like these, Doherty noted, " you can prime up

absolutely all the T cells in the world, and it won't make any difference. You

need something much more powerful. " But as researchers still grapple with a

better vaccine for more common flu strains, finding a strong prevention for such

a virulent one remains an even more daunting challenge.

http://blogs.scientificamerican.com/observations/2011/09/12/the-flu-sheds-light-\

on-holes-in-immune-system-knowledge/