Immunology 2.0: brain, gut?

In order to progress, should the field of immunology look to other organ systems such as the brain and gut, or should it focus its efforts on all that remains unknown about the immune system itself?

Macrophage cell in early stages of infection
with African swine fever virus
Image: Wikimedia commons

"The major advancements in any field come when branches of science collide," said linkurl:Kevin Tracey,;http://www.feinsteininstitute.org/Feinstein/Laboratory+of+Biomedical+Sciences an immunologist at the Feinstein Institute for Medical Research, one of the researchers asked to write their opinion about the future of immunology for the tenth anniversary issue of Nature Immunology. Tracey's interests lie in the intersection of neurophysiology and immunology, which took the spotlight after linkurl:the discovery;http://www.nature.com/nature/journal/v405/n6785/full/405458a0.html that action potentials of the vagus nerve regulate the release of cytokines from the spleen and other organs. "That's just the beginning. I think there is going to be a lot of nerves and a lot of circuits that control the immune system," Tracey told The Scientist. If so, future medical devices to control these circuits may act like immune-system pacemakers, Tracey predicted, and when implanted along nerves could treat inflammatory diseases including arthritis, colitis, diabetes, heart disease and arteriosclerosis. linkurl:B. Brett Finlay,;http://www.finlaylab.msl.ubc.ca/ in contrast, argues that the future of immunology lies in the gut. The mucosal lining of the intestines harbors special lymphoid tissues containing white blood cells, and Finlay, a microbiologist at the University of British Columbia in Vancouver, said he believes a better understanding of the interactions between the immune system, the gut and other mucosal surfaces will push the field of immunology forward. Knowing how the gut interacts with other mucosal membranes is important because an immune reaction in one of these areas can cause changes in others. "When you realize that [the mucosal surfaces] talk to each other, it has quite significant impacts on how we interpret their actions and reactions to infection," Finlay said. Indeed, differences in intestinal microbes can have substantial effects on the immune system. Even which company a lab buys their mice from can influence the mice's gut microbiota, which in turn influences their immune system and immune response. "Knowing what we know now, it might explain why one lab finds one thing and another finds another," said Finlay. But not all immunologists say that research needs to cross into other organ systems to progress -- in the same issue, other researchers champion for burrowing down into the details of a still-unknown field. linkurl:Ruslan Medzhitov,;http://info.med.yale.edu/bbs/faculty/med_ru.html an immunologist at the Yale University School of Medicine, argues the field should go back to basics -- that future advancements in immunology lie in the less-well studied areas of basic immunology research. "There are some areas that are well understood and there are some that we know almost nothing about," Medzhitov told The Scientist. "There is a fundamental gap in basic understanding." These "gaps" include how the immune system protects against each different type of invader, how and why some immune responses are protective while others aren't, how bodies sense and interact with commensal and pathogenic microbes, and a better understanding of the body's black box of type two immunity -- the response to parasites and allergens, characterized by a stronger antibody response. "There is no knowledge of how allergens work," said Medzhitov. Medzhitov believes that this lack of understanding of basic immunological principles has also led to the continual failures during HIV vaccine trials, because even trials that elicit a strong immune response won't be therapeutic unless it is a protective response. "We can induce a protective immune response to bacteria, but we don't know at all how to induce a protective immune response to retroviruses," Medzhitov said. "Applied research is only as good as the basic research that informs it." Certain tools may help immunologists obtain a fuller understanding of basic research, said linkurl:Matthew Krummel;http://pathology.ucsf.edu/krummel/ University of California, San Francisco. For instance, real-time imaging can illuminate the sequence of events that the immune system undergoes, showing how and why the immune system attacks some antigens while ignoring others, and what happens when this goes wrong, he added. Looking closer at the epigenetics of the immune system could also lead to the breakthrough researchers have been looking for, said linkurl:Alexander Tarakhovsky,;http://www.rockefeller.edu/research/faculty/abstract.php?id=327 an immunologist at Rockefeller University. Exposure to microbes and antigens -- whether through the gut or elsewhere -- can change the epigenetics of immune system cells, and understanding this process could help scientists design drugs to selectively "wipe-out" our immune system's memory, providing treatment options for allergies, lupus and other autoimmune disorders. "Most of the immune conditions are the result of interaction of the developing immune system and the environment," said Tarakhovsky. "And epigenetics is all about the environmental impact on genetic traits."
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[25th February 2009]*linkurl:25 Years Ago in Immunology;http://www.the-scientist.com/article/display/54679/
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[7th April 2003]