Strong immunity = low fertility

A study in wild sheep may help explain why natural selection has not eradicated weak or self-destructive immune systems

A fluctuating trade-off between reproduction and survival in a feral population of Soay sheep may resolve the age-old question of why natural selection has failed to eradicate genes for both infection-prone and self-assailing immune systems.

The potential answer, published in Science this week (29th October), comes from the nascent field of ecoimmunology, which examines how different levels of antibodies in the blood of wild animals can influence their ability to survive and produce young.

Specifically, the authors found that, among a population of isolated, wild sheep, individuals with higher levels of antibodies associated with autoimmunity in other species were more likely to survive harsh weather conditions, but also reproduced less. Consequently, the benefits of high immunity, such as quick and efficient riddance of infection, may come with a cost -- less energy for reproduction.

"This paper reveals that more [antibodies] might not always be better, and that to understand the evolution of immune systems, it will be critical to study them in free-living, outbred organisms," Lynn Martin, an ecoimmunologist at the University of South Florida, who was not affiliated with the study, said in an email to The Scientist.

Researchers have found that feral rodents can hold comparatively high concentrations of antibodies in their blood, but, mysteriously, autoimmunity diseases such as type 1 diabetes and lupus are only seen in humans and lab, domestic, and captive mammals, said Andrea Graham, an evolutionary biologist at Princeton University and first author on the study.

There was "this nagging question of whether autoimmunity was some weird freak of captivity," added Andrew Read, evolutionary biologist at Pennsylvania State University, who did not contribute to the study.

Using blood samples collected every August for 11 years from the Soay sheep population on Hirta, an island in the St. Kilda archipelago of Scotland, Graham and colleagues from the University of Edinburgh in Scotland measured the concentration of antinuclear antibodies (ANAs), or autoimmune antibodies that attack the contents of the cell's nucleus as if it were foreign material. They then compared these levels to other variables of fitness such as survival and reproduction.

Researchers found that adult females with higher levels of ANAs lived longer by surviving more bitterly cold, parasite-infested winters. However, these same females were less likely to have babies the following spring. The correlation was only present during particularly harsh winters, however, when sometimes nearly 50 percent of the population died, suggesting heterogeneity in immune response is produced by natural selection acting on an ever-changing environment.

Ewes with high levels of ANAs also produced young with higher chances of survival through the next winter than young born to mothers with weak immune systems, suggesting a genetic basis for the varied immune responses in the sheep population.

"Immune response is only one part of the fitness component," said Peter Hudson, a disease ecologist at Pennsylvania State University, who was not affiliated with the study. "When [an individual] is not being exposed to pathogens, then high immune response could be too costly."

According to the results, when parasite prevalence is low and food is abundant, individuals with low immune responses will have the highest fitness because they will have the energy to produce the most young in the shortest period of time. But when the threat of infection is high and the winters are brutally frigid, individuals with high immune responses will survive and live on to have more children, while others die off. Thus, these trade-offs exhibited by the Soay sheep can account for their heterogeneity in immune response.

Read and Martin agreed that the next step is to experimentally manipulate antibody response in large populations to discover whether a causal, rather than correlational, relationship is present in this survival-reproduction trade-off.

The field of ecoimmunology "has been a controversial field because it's really hard to decide what to measure without a history [of the population]," noted Read.

This study demonstrates its potential benefits, however, Graham argued. "I firmly believe that we wouldn't have been able to find out such cool things about the immune system without this long study on the Soay sheep," she said. "Now that we understand all the nuts and bolts of the immune system [from traditional immunology], we can go on to try to understand it in the real world, because that's what really matters."

A. Graham et al., "Fitness Correlates of Heritable Variation in Antibody Responsiveness in a Wild Mammal," Science, 330:662-65, 2010.

Source: The Scientist