Too much stress can make you physically ill. Here’s how.

Figuring out just how we go from stressed to sick on the physiological level is the subject of a new study published in the Journal of Leukocyte Biology. The key, according to this study, can be found in the way our immune systems interact with our nervous systems. While the immune system is great at defending against microscopic bugs, “fight or flight is not going to help me sift through all of those emails and feel bad about returning them late,” lead study author Adam Moeser told me.

In order to take a closer look at this link between stress and illness, Moeser’s team studied an innate immune cell type called mast cells that live in abundance in your gut wall and your skin. Moeser, an associate professor and the Matilda Wilson Endowed Chair in the college of Veterinary Medicine at Michigan State University, describes these mast cells as “surveillance cells that help the body defend against any type of challenge or stress.”

These cells are among the first to be activated not only in the case of infection, but also to “any perceived threat,” even one psychological in nature. In other words, they act as “alarm cells” in the body, responding within seconds to the onset or exposure to stress.

“There was even a study that showed mast cells in our gut become activated when someone is nervous about public speaking,” Moeser explained. “So it’s really this mind-body signal connection.”

Like anything good, too much of an immune response can be a bad thing. Mast cells are important immune defense barrier on the one hand, but when the stress response becomes “too overwhelming, where we can’t cope or return to our homeostatic place,” Moeser said. “The mast cells switch from being protective to actually pathogenic.”

Too many overactive mast cells are indicated in irritable bowel syndrome (IBS) and asthma, but they are often just the tip of an immune cascade. What was once a helper becomes a hindrance, leading to increased inflammation. Mast cells trigger the release of histamines (causing itching and swelling), encourage mucus production and produce pain by acting on sensory nerves in the body that signal the brain to amp up your pain response.

To better understand this process, Moeser’s team homed in on a specific type of stress receptor that lives on the mast cell, known as CRF1 (corticotropin-releasing factor receptor subtype 1). This receptor releases a substance when it perceives stress — which could be a sudden meeting with your boss or an actual pathogen.

Researchers modified these receptors in mice and in human mast cells (grown in petri dishes) in order to measure their response to different types of stressors, including psychological and immunological stress. When the receptor numbers were reduced, the mast cells’ activity during stress was also reduced, leading to “less disease outcomes in the physiology,” Moeser said.