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Sixth Sense: What Your Immune System Knows By Rick Weiss Lots of people talk about having a "sixth sense," a way of perceiving the world other than by the standard channels of seeing, smelling, tasting, hearing or touching. Now a growing cadre of scientists is coming to believe that the body actually has such a sense. They're not talking about extrasensory perception or intuition, though. Rather, the body's humble and hard-working immune system deserves recognition as a sensory organ of sorts, these scientists say. According to this emerging view, the immune system is much more than just a mechanism for fighting off microbial invaders. It is a specialized network of bio-sensors designed to pick up information from within and around the body and relay that information to the brain, where it can motivate animals or people to behave in specific ways. Just as a loud sound might lead one to look around for trouble, or a flash of light might make one cover one's eyes, so signals from the immune system's scattered "listening posts" may trigger useful behaviors, the theory goes. In some cases those behaviors may be as simple as huddling, shivering or sleeping--actions that are typically considered general symptoms of illness or debilitation but that may, in fact, be highly specific and beneficial responses to infection. In other cases, the immune system may inspire behaviors not typically associated with illness at all, such as passivity, aggression or sexual attraction. Some experiments have even suggested that the immune system is a big part of the body's way of telling a woman's brain which man she'd like to date. "We think the immune system is essentially a sense organ," said Steven F. Maier, a neuroscientist at the University of Colorado at Boulder. "It's just spread around the body more than most senses are." Scientists have known for years that the brain can communicate with the immune system. Some white blood cells responsible for attacking microbes, for example, are sensitive to certain brain chemicals, such as stress hormones--a finding that may explain why the immune system suffers in people under chronic stress. But communication in the other direction--from the immune system to the brain--has been harder to document. That's changing, now, with the development of sophisticated molecular tests that can track tiny chemicals secreted by the immune system and their effects on the central nervous system. One area of research involves "sickness behaviors," such as the sleepiness, feverishness, shivering, and loss of libido and appetite that often accompany infection. Many doctors have ignored these as unavoidable side effects of the body's efforts to fight disease--collateral damage from an immune system at war. In recent years, however, several studies have suggested that the body, when sick, actually strives to foster these behaviors. Key to the system is a chemical called interleukin-1 (IL-1), which is secreted by immune system cells such as macrophages--large white blood cells that attack foreign particles--when they detect a microbial invasion. Scientists have long known that IL-1 helps coordinate the body's immune defenses, rallying other cells to join the fight and triggering the inflammatory reaction that helps keep microbes from spreading. But it turns out that IL-1 also has direct effects on the spinal cord and brain. For example, IL-1 induces shivering and fever--useful because elevated body temperature reduces bacterial growth--as well as general inactivity and loss of appetite and libido--which makes sense because an animal is better off avoiding the risk of going out, being seen and perhaps being attacked when it is sick and less able to defend itself. Moreover, these are not just reflexive, knee-jerk reactions, but truly "motivated" behaviors that are coordinated by the brain and vary depending on context. For example, if an experimental animal is made sick and placed in a cold room where it is unable to raise its temperature as needed, it will go so far as to perform a learned task, such as pressing a bar repeatedly in its cage, if that action is rewarded with access to warmth. That level of strategizing suggests the behavior is based on information coming from a sophisticated sensory system. The immune system also seems to affect how animals and people choose their mates. Cupid, it seems, lives partly in a section of the immune system that varies a lot among individuals (the same part that determines whether a transplanted organ is compatible or will be rejected), and that gives animals equally variable scents that some can detect and unconsciously analyze. Rodents use these scents to identify and preferentially mate with others whose immune system profiles are quite different than their own--perhaps with the aim of preventing inbreeding and maintaining genetic diversity. Immune system scents may also provide information about a potential mate's vigor and resistance to disease. For instance, some rodents can sniff out which rodents in a group have become infected with a virus, even if the infected rodents show no symptoms yet, said Gary Beauchamp, director of the Monell Chemical Senses Center in Philadelphia. In people, too, the immune system may play a role in sexual attraction. In one European experiment, women sniffed T-shirts worn by various men for several days and were asked, based on smell alone, which of the men they'd like to go out with. They almost always chose the shirts worn by men whose immune systems were most different from their own. (The exception: Women on birth control pills chose T-shirts of men whose immune profiles resembled their own--perhaps because the pill mimics pregnancy and these women were drawn to same-smelling, potentially helpful kin.) Depending on what it's been exposed to in the past few hours or days, the immune system can also alter hormone levels--including levels of testosterone, which can influence irritability and aggressiveness. One theory holds that the lowering of testosterone that often comes with infection is the immune system's way of telling the body, "Don't get into a fight now, or you're gonna lose," said Wayne Potts, a University of Utah immunogeneticist. Further studies may reveal that the immune system has quite a bit to say not only about how we behave but about how we feel and even who we are. Some suspect, for example, that many of the day-to-day changes in mood that people chalk up to the vicissitudes of life are responses to subliminal signals from the immune system following exposure to various foreign proteins in food, water or air. Perhaps most intriguing, many of the chemical switches in the brain that influence personality--such as those relating to serotonin, which plays a role in depression--are also found on immune system cells. In this sense, immune system cells are a mirror on the mind, said Edwin Blalock, an immunologist at the University of Alabama at Birmingham School of Medicine. Someday, Blalock said, doctors may be able to diagnose various brain conditions simply by conducting tests on people's immune system cells. And medicinal chemists looking for new drugs for depression and other brain ailments may find some excellent candidates in an unexpected place: in the natural medicine chest of chemicals secreted by immune system cells.
The Sick Sense Many of the seemingly nonspecific symptoms of illness may be highly specific and useful behaviors prompted by the body's "sixth sense," the immune system. 1) Immune system cells, such as this macrophage, detect the presence of microbial invaders. 2) In response, these cells secrete bio-chemical signaling molecules, such as interleukin-1. 3) Those molecules reach specific target areas in the brain, where they
induce various recuperative and protective behaviors such as shivering, sleepiness and a
reduced propensity to fight attackers. © Copyright 1999 The Washington Post Company
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