Variety, the spice of immunology

In humans and wild animal populations, immune responses can vary greatly between individuals, species, and environments -- yet, the vast majority of immunological studies are conducted on well-fed, parasite-free, genetically similar lab mice. Recently, however, ecologists and immunologists have begun to join forces to study the long-suspected variability of immune systems in wild populations."Lab mice live in really happy conditions" compared to animals in the wild, said linkurl:Tom Little,;http://www.biology.ed.ac.uk/research/institutes/evolution/homepage.php?id=tlittle an evolutionary biologist at the University of Edinburgh in the UK, but "we can't just study things under really happy conditions [because] it's just not what's normal...What if everything we know about the immune system only really happened in the lab?"

Image: Wikimedia commons, Aaron Logan

Indeed, a recent comparison of the immune functions of wild and lab mice revealed that wild mice generally had stronger immune responses than their laboratory counterparts."There's got to be at least 100,000 papers that looked at the immune system of mice in the lab, but no more than five papers that looked at it in wild mice," said the study's lead author linkurl:Mark Viney,;http://www.bristol.ac.uk/biology/person/index.html?personKey=eP5sQc9n6QY99wrbcgSUOITDZAY8Nz a parasitologist at Bristol University in the UK. These differences may have a direct impact on how immunologists interpret the findings of their laboratory studies, he added.The study of ecoimmunology, as it's called, started in the 1990s when ecologists began to take an interest in understanding this variation in immune responses in the wild, and how it influences or is influenced by community structure. Without a good toolbox of immunological techniques, however, early experiments were rudimentary, leading researchers to question their biological relevance. But more recently, immunologists have joined in, bringing their own perspective to the field, along with more advanced methods for the study of immunology in wild animals. Indeed, the collaboration has already produced at least one successful field study of immunity. Working with a group of evolutionary biologists at the University of Edinburgh, immunologist linkurl:Andrea Graham;http://ccoon.myweb.usf.edu/ecoimmunology.org/AGraham_About_Me.html of Princeton University found that wild soay sheep on the Scottish island of Hirta were more likely to survive the harsh, parasite-infested winters if they had high levels of a certain kind of antibody, known as antinuclear antibodies (ANAs). However, these sheep also reproduced less frequently, suggesting a strong immune system may come at a cost.

Image: Wikimedia commons, Eirian Evans

The correlation only occurred during especially harsh winters, however, when up to 50 percent of the population dies, suggesting that immune variability may evolve more readily in fluctuating environments. The study also challenged the theory that autoimmunity only exists in lab and domesticated animals and some human populations, as the sheep expressed levels of ANAs associated with autoimmune disorders in other species.Studying the variance of immune systems in human populations may also be enlightening, Viney said, informing research on vaccine development, for example. "Humans in developing and developed countries are mirrors of wild animals and lab animals when it comes to their relative susceptibility to disease and parasites," he said. Because immune systems function differently under the stress of disease and malnutrition, vaccines could be more effective if targeted for different populations of people.The newfound teamwork may also benefit the immunologists, Viney added. "Mainstream immunology needs to think in an evolutionary fashion," he added. "Sometimes you have to stand back, and think of the broad picture" -- something ecologists do very well.Ecologists might help immunologists understand the microflora of the human digestive tract, for example, said linkurl:Judith Allen,;http://www.nematodes.org/allenlab/people/allen.htm a professor of immunology at the University of Edinburgh. "Ecologists understand communities, and these gut bacteria are communities within our bodies," she said. Personalized medicine may be another area ripe for collaboration, added linkurl:Brian Lazzaro,;http://gradeducation.lifesciences.cornell.edu/faculty/individual5641 an evolutionary geneticist at Cornell University. "The ability to [tailor treatments to individual patients] will obviously hinge on understanding how individuals vary immunologically and in their interactions with specific pathogens and reactions to various treatments," he said. Though ecoimmunology may be young, it seems to be drawing more and more attention. Last year, the National Science Foundation funded a collaborative network of ecologists, evolutionary biologists, and immunologists aiming to develop new techniques and immunological research questions specific to animals in the wild. And next month, Functional Ecology plans to publish a special issue devoted entirely to ecoimmunology in hopes of attracting more researchers to the field.Not everyone is convinced, however. "I'm not sure I would agree that ecoimmunology actually constitutes a field," said Lazzaro. "I think the origins are more in traditional evolutionary biology where there has been longstanding interest in selection imposed on hosts by pathogens and parasites [and] how activation of the immune system may limit other traits," like reproduction. But with the newly developed "technological ability to apply the tools of traditional immunology in natural systems," he added, the field may really start to take shape.A. Graham et al., "Fitness Correlates of Heritable Variation in Antibody Responsiveness in a Wild Mammal," Science, 330:662-65, 2010.S.R. Abolins et al., "Measures of immune function of wild mice, Mus musculus," Molecular Ecology, AOP, doi: 10.1111/j.1365-294X.2010.04910.x, 2010.
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