Immune System Shaped by Environment More Than Genes

At a Glance By analyzing twin pairs, researchers determined that most of the variability in the immune system is due to environmental factors, rather than genes.

The findings highlight the reactive and adaptive nature of the immune system in healthy people.

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The immune system is a complex network of cells, tissues, and organs that work together to protect our bodies from infection. The system must fight off invading microbes, infected cells, and tumors while ignoring healthy tissues.

There can be significant variation in immune system function between people. It’s not known how much of the variation is caused by genetic differences (heritable) and how much is due to exposure to environmental (non-heritable) factors such as microbes.

To determine the basis of immune system variation, a team led by Dr. Mark M. Davis at Stanford University School of Medicine applied the most recent advances in immune monitoring technologies to a classic research model: studying twin pairs. The study was funded in part by NIH’s National Institute of Allergy and Infectious Diseases (NIAID). Results appeared in Cell on January 15, 2015.

In twin studies, researchers compare identical (monozygotic) twins, who share almost all of their genes, with fraternal (dizygotic) twins, who share about half of their genes. Twin pairs share the same prenatal environment and usually have a similar childhood environment. Thus if identical twins show more similarity on a given trait compared to fraternal twins, it suggests that genes significantly influence that trait.

The team took blood samples from 210 healthy twins, ranging in age from 8 to 82, who were part of a twin registry. Of the 105 twin pairs, 78 were identical and 27 were fraternal. The researchers measured more than 200 different immune system parameters, including the frequency of different immune cell types—such as B cells and T cells—and levels of 43 cytokines, chemokines, and other serum proteins that modulate the immune response. The team assessed the impact of heritable versus non-heritable factors overall, after receiving the seasonal influenza vaccine, and during a microbial infection.

The researchers found that non-heritable influences outweighed heredity in about 75% of all the immune parameters, and almost exclusively determined more than half of the parameters. Some of the immune measures showed more variability with age, suggesting that over time environmental factors drive many immune system variations.

In the seasonal flu vaccine analysis, no detectable contributions from heritable factors were seen in the resulting antibody responses, suggesting that antibody responses are likely due to environmental factors such as previous vaccinations or infections.

To assess the effects of microbial exposure, the team surveyed immune responses to cytomegalovirus (CMV), which infects 50% to 80% of all adults in the U.S. by the age of 40. Identical twins with only one twin positive for CMV had much greater immune system variation between them than identical twins who were both negative for CMV. This demonstrates how a single microbial exposure can affect the immune system of a healthy person.

“The immune system has to think on its feet,” Davis says. “A healthy human immune system continually adapts to its encounters with hostile pathogens, friendly gut microbes, nutritional components and more, overshadowing the influences of most heritable factors.”

—by Carol Torgan, Ph.D.