Immune system ready for its close-up

Deciphering the inner workings of the body's disease-fighting system receives a welcomed assist from a new generation of microscopes.

By Susan J. Landers, amednews staff. Aug. 12, 2002.

Washington -- It may not be a Steven Spielberg production, but "The Immune System: The Movie," holds early promise for understanding how humans fend off invading microbes -- high drama indeed.

Using newly developed technologies, scientists are now able to see the immune system in action.

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"We see movement. We see things in three dimensions and over time in a way you can't if you just take a thick section of tissue," said Ronald Germain, MD, PhD, deputy chief of the Laboratory of Immunology at the National Institute of Allergy and Infectious Diseases.

Using a confocal microscope, Dr. Germain and his fellow NIAID researchers are able to watch how the cells behave, where they go and even, up to a point, how their daughter cells behave.

Dr. Germain and colleagues published their findings earlier this summer in the June 7 Science. Their paper joined two others in reporting immune system findings detected by using sophisticated microscopes that can scan through a thick sample and limit their focus to living cells lying deep within the lymph nodes. All of the researchers used tissue from mice.

Dr. Germain says his microscope looks pretty much like most large research microscopes, but it is connected via cables to high-powered lasers that can scan an image very rapidly taking thin visual slices.

A multiphoton microscope costs a half-million dollars.

"You actually use optical tricks to figure out where you are, then the computer reconstructs the thicker object from that high resolution information at each level. So you can look at each level or you can put it together," said Dr. Germain.

The images are viewed on a TV screen rather than directly through the microscope.

The study by Dr. Germain and colleagues examined how T cells interact with dendritic cells within lymph nodes. Dendritic cells are key components of early immune responses that mop up invading microbes, display fragments of those microbes to T cells and help trigger the T cells' response.

Another Science paper, written by University of California, Berkeley, researchers, examined the maturation of T cells in the thymus while a third paper, written by researchers from the University of California, Irvine, studied properties of T and B cells that are critical for initiating immune responses. Both of these studies employed two-photon microscopes.

The big picture

Dr. Germain's findings served to reinforce his team's theory that individual T cells remain in contact with dendritic cells for prolonged periods -- an issue that has provoked debate in the field, he said. "We thought it should be this length of time so it was pleasing that it came out that way."

What was surprising to Dr. Germain and his colleagues was the high activity level of T cells that was observed even as they were attached to the dendritic cells. "You see all of these little processes sort of flying out from them," he said.

Dr. Germain noted that over the years researchers examining the immune system have shifted from looking at the entire immune system to taking it apart and looking at individual molecules. "Now it's time to start putting it back together again."

Using the latest technology is apparently a good way to examine the big picture as it allows researchers to watch the highly mobile cells within the immune system that can do a variety of tasks from different sites, said Dr. Germain. "This sort of geography of the system is not something we have a full appreciation of because we have never been able to really look at it except in these static pictures.

"We suspect there will be surprises as we look at things we couldn't really ask about or understand before," he predicted.

Dr. Germain also cautions that the published findings are early ones and that there are some limitations to what can be viewed with the equipment now being used.

However, researchers' ability to view even more immune system activity will broaden with the arrival of a multiphoton microscope, which Dr. Germain's lab has already ordered. Given the cost of the high-tech microscope -- at least a half a million dollars -- not all labs will be as well equipped as NIAID's for awhile.

But many labs have the confocal scanning microscope with which Dr. Germain and colleagues conducted the research that appeared in Science, and the NIAID researchers have received a number of queries from others about their work.

"The Immune System: The Movie" is likely to have other viewers before long.