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Cell Wars


Immune cells vs. invaders: it's a war going on in every healthy human body. When the combatants travel to space, say NASA scientists, curious things happen...

by Karen Miller

When you wake up, maybe you yawn, switch off your alarm clock, and listen for the perking of an automatic coffee maker -- a normal morning routine on Earth.

But if you were in orbit, the first thing you'd do is take a little roll of cotton, swish it around in your mouth, and then drop it in a tube filled with preservative. The cotton collects viruses, and the goal of that good-morning ritual is to help determine why astronaut saliva contains more viruses in space than it does on the ground.

It's not a trivial question.

Our bodies are chock-full of tiny invaders: bacteria, viruses, protozoans. Multitudes inhabit our gut, more slip in on the food we eat and through the air we breathe. Usually they're not a problem. Indeed, some are even helpful -- and the ones that aren't are kept in check by our vigorous immune system, which marks and destroys pathogens before they get out of control. Without immune systems, humans would die.

In space, our immune system functions differently. This complex system consists, essentially, of disease-fighting cells that can travel throughout the body. There are many kinds of immune cells; two of the most important are B-cells, which send out antibodies -- proteins that latch onto germs or other problem-causing invaders, flagging them as invaders to be destroyed, and T-cells, which are the soldiers of the system, physically attacking and destroying pathogens.



Credit and copyright: Scott Barrows

Small, capsule-shaped bacteria in this artist's rendering are being "swallowed" by an immune cell's oozing outer membrane.


In space, these cells don't work the way they do on the ground. T-cells, for example, don't multiply properly; there aren't as many of them as there should be. They can't move well. They don't signal each other as effectively. Overall, they seem less able to destroy invading germs.

Here on Earth, doctors have learned that stress can suppress the immune system by causing the body to release hormones that affect the way T-cells behave. Likewise, the unique physical and psychological stresses of space flight (takeoff and landing, for example) might trigger immune-altering hormones. Another possibility is that something about space itself -- weightlessness, perhaps, and not hormones at all -- might affect immune cells directly.

To help solve the mystery, researchers are using a NASA-developed "rotating bioreactor," which provides a reasonable analogy of microgravity here on Earth. Neal Pellis, chief of the Biological Systems Office in the Johnson Space Centre, explains: The core of the bioreactor is a soup-can size container that spins at the leisurely rate of 14 rpm. It allows cells to remain suspended for months at a time in continual free fall. Within their fluid environment, the tumbling cells fall toward Earth as fast as they can -- just as they would in Earth orbit.



See the movie and learn more from CellsAlive.com

On Earth, a smaller T-cell (arrow) attacks and kills a much larger influenza virus-infected target.


Using the bioreactor, researchers can separate the immune system from its hormonal controls. Rather than looking at the human immune system as a whole, Pellis and his colleagues can examine the possible effects of low-gravity on individual immune cells.

In the bioreactor, says Pellis, cells begin to change within the first 15 minutes. Indeed, one of the first alterations researchers observe could possibly trigger all the other effects: T-cells are somehow forced to remain round.  

It's an important change. On Earth, these cells can alter their shape. They're able to protrude portions of themselves -- an ability that they use to move around, just like amoebas do. And they need to move in order to do their job: They travel to the sites of infections, where they attack germs. They move to the sites of tumours. They locomote in and out of immune system organs, such as the appendix and tonsils, where other T-cells share samples of invading pathogens.



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This animation illustrates the basic cell-to-cell interactions that lead to antibody production. T-cells must move and communicate with their cellular cousins to make the process work.


But it's not only the ability to move that's hampered by roundness. This simple change also makes it harder for cells to communicate. Round cells, explains Pellis, find it harder to touch each other. Their ability to interact is reduced.

Imagine two balloons, he says. "If you put them side by side, and pressed them together, the surface area that's in contact can be quite large." But, he says, if you have two bowling balls, no matter how hard you press them together, only a tiny fraction of their surfaces will meet. Such cells have less ability to exchange the chemical signals that command them to go into action

It's still unclear what these findings mean for the health of space travelers. Astronauts do show an increase in virus levels. For example, notes Duane Pierson, head of microbiology for the Johnson Space Centre, when astronauts cough or sneeze, the droplets released contain 8 to 10 times more of the common Epstein-Barr virus (which causes infectious mononucleosis) than normal Earth sneezes. Although that's an indication of immune system suppression, the astronauts themselves have remained completely without symptoms.



Learn more from the National Institutes of Health

Elements of the human immune system


Nor is it yet clear exactly what keeps T-cells round. Without the usual effects of gravity, explains Pellis, other forces --perhaps intermolecular or submolecular forces, such as hydrogen bonding -- must play a larger role, so that in microgravity, these other forces control the shape that the cell takes. "But exactly which forces are doing what to whom, where and how, to arrive at a spherical cell, I don't think anybody knows.”

Finding out is important ... and not only for astronauts. This research will also help people on Earth.

T-cells protect us from all kinds of problems, says Pellis, but they don't always behave as we would like. "There are times when we don't want them to invade -- transplants, for example. And there are cases when we want them to act vigorously, like in tumours."

Understanding the way physical forces affect T-cells could eventually allow scientists to control them -- "taming" them so that they help us, as they're meant to, in far more effective ways.

 

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First Science 2014