New research is discovering a complex and intimate connection between our state of mind and the functioning of the immune system.
Unpublished research recently summarized in the journal Nature conducted at the Technion Israel Institute of Technology in Haifa unearthed a fascinating connection between the brain and recovery from heart attacks in mice.
Examining scarring on the hearts of the rodents, researchers discovered a significant difference in the level of damage between one group of mice that had received stimulation of a brain area involved in positive emotion and motivation, and the control group that received no stimulation.
The control group showed significant evidence of damage to heart cells under the microscope while the brain-stimulated mice had far less detectable injury.
“In the beginning, we were sure that it was too good to be true,” Hedva Haykin, a doctoral student conducting the research, told Nature. It was only after repeating the experiment several times, Haykin said, that she was able to accept the effect she was seeing as real.
Haykin’s work is part of a growing boom in medical research exploring the connection between the brain and the immune system. Scientists are discovering multiple lines of communication between the nervous and immune systems—and different parts of the brain communicating different instructions to our body’s defensive systems.
“This field has really exploded over the last several years,” said Filip Swirski, an immunologist and director of the Cardiovascular Research Institute at Mount Sinai in New York, in a phone interview with The Epoch Times.
Swirski pointed out that the immune system and the nervous system are “arguably the only two systems of the body that we know have the capacity to learn.
“The immune system can, for example, acquire memory of previous infection,” said Swirski, “which allows it to rapidly respond to new infections.”
Swirski and other researchers published findings in Nature in May 2022 that explored how distinct regions of the brain shape immune response on a granular level—with different cells of the immune system being directed by different regions of the brain.
While circuits in the motor cortex of the brain rapidly mobilize leukocytes (a type of white blood cell) to the site of an acute infection or injury, another part of the brain, the hypothalamus, essentially down-regulates immune response by returning leukocytes to the bone marrow where they are produced and, apparently, “housed” for future deployment.
“One of the things we are seeing,” said Swirski, “is that the brain can modulate, or calibrate, the immune system.
“We are now recognizing,” he added, “that the brain has this very close conversation with the immune system.”
Swirski’s research, he said, “mapped some of the brain’s remarkable ability to control the distribution of all the main immune cells in the body. Small clusters of neurons in specific regions of the brain, responding to stress, can dictate where the immune cells will appear in the body.”
He went on to say, “It’s a remarkable control that we aren’t aware of going about our daily lives; it doesn’t enter our consciousness. If you experience a stressful or traumatic event in your life, you have a felt physical response to that—but you aren’t aware that your brain is telling your body where to send the immune cells in response to that event.”
Swirski explained that while the immune system’s response to acute illness or injury is necessarily intense and rapid, too much of that kind of response can lead to the exhaustion of the immune system itself.
This is why his team’s research showed that when specific regions in the brain redistributed immune cells throughout the body in response to stress, the body was less prepared to fight off acute infections, like COVID-19. On the other hand, acute stress protected against the acquisition of autoimmunity. While this does not mean that stress is good for you as a therapeutic against autoimmune disease, it does highlight the remarkable control the brain has over the immune system.
The Delicate Balance Within the Immune System
“The immune system,” said Swirski, “exhibits something called ‘anticipatory inflammation’—for example, the body responds to a viral infection by having certain immune cells congregate in the lymph nodes and show that virus to T cells and B cells that then generate immune response to that virus that is more immediately available to be mobilized should the infection return.”
In a follow-up email, Swirski said that anticipatory inflammation is the idea that the “immune cells ‘anticipate’ an infection or injury by relocating to organs that are in potential danger. It’s a handy term to describe how the immune system is ‘strategizing’ against a possible assault.”
But there’s a danger in this anticipation on the part of the immune system as well; this anticipation can “set the threshold for auto-immune” reaction higher.
“When we exposed animals to a model of multiple sclerosis [an auto-immune disease],” Swirski explained, “and then stressed those animals, we found fewer B cells and T cells in the lymph nodes, and thus a less severe manifestation of disease. But when we exposed animals to a viral infection and then stressed them we also found fewer B and T cells, which, in this case, led to a worsened outcome because the immune system was less efficient at clearing the virus. The same phenomenon (redistribution of immune cells in the body) led to a different outcome depending on context. This kind of duality often exists in the immune system.”
This balance also applies to the immune system in relation to the external environment. The immune system is always distinguishing between “self” and “not-self” in the body, Swirski explained. “There is this idea that if the immune system is not adequately engaged with the environment, it may start to make mistakes and act against antigens that are not inherently harmful.
“A certain amount of stress may actually be good for the immune system,” Swirski said. “It keeps the immune system busy” and may help to develop resilience in the system.
“The immune system operates optimally somewhere between engagement and exhaustion,” he said. An under-engaged immune system may become susceptible to attacking the body itself (conditions such as rheumatoid arthritis, lupus, MS, allergies, and, to a certain extent, asthma are examples). Conversely, an overtaxed immune system simply becomes exhausted and suffers a catastrophic failure.
Swirski gave an example of what happens with sepsis—a serious condition in which the body responds improperly to an infection.
“Sepsis is an overwhelming immune response to overwhelming infection. The problem with sepsis is not only the cytokine storm we heard so much about with severe COVID (in ER, we can often mitigate the effects of this process) but the fact that following the cytokine storm, the immune systems can shut off—and then nothing can be fought.”
In fact, doctors and scientists noted relatively early in the pandemic that individuals who were hospitalized with COVID had an immune system that responded in a markedly different way to the virus than others who had milder cases. Researchers at the University of California, San Francisco, noted this phenomenon in the university’s periodical.
Early in the pandemic, doctors noticed that compared to forms of Acute Respiratory Distress Syndrome (ARDS) caused by other respiratory infections like flu, some features of COVID ARDS were atypical. Patients were not only slower to develop the syndrome but also slower to recover, in some cases spending weeks on a ventilator. Often, their immune systems continued a ruinous battle against their own bodies—ravaging their lungs and choking them of oxygen—even after SARS-CoV-2, the virus that causes COVID-19, had cleared their systems.
“It was very strange,” UC San Francisco’s Dr. Carolyn Calfee, a critical care physician and one of the world’s leading experts on ARDS, told UCSF magazine. “I thought, ‘What kind of ARDS does this?’” she recalls. “‘This is not normal.’”
In searching for answers, Calfee and other researchers are finding that COVID-19 unhinges the immune system in ways no one expected, going so far as to turn the body against itself. Some people who get especially bad or unusual symptoms, for instance, harbor “rogue antibodies”—similar to those seen in autoimmune diseases—that disrupt the body’s normal immune response and can attack the body’s own tissues. These discoveries could explain how the virus causes such extensive outcomes; they could also help predict who, if infected, will develop severe symptoms and may help identify effective treatments. Potentially, they could also change scientists’ fundamental understanding of human immunity and how it can malfunction.
The Hygiene Hypothesis
Another fascinating example of the interplay between immunity and the environment as a means of calibrating optimal stress for the immune system is something called the “hygiene hypothesis.”
“The immune system must engage with the world and relies on that engagement,” said Swirski.
The hygiene hypothesis suggests that the reason we are seeing the rise of allergies and asthma in children is that more contemporary lifestyles have eliminated many of the childhood diseases and pathogen threats we evolutionarily engaged with as a matter of course and, as a result, the immune system can exhibit a “breakdown of tolerance” to the body and recognize something that isn’t a pathogen as a pathogen.
In such a case, according to Swirski, the immune system “has learned, but in the wrong way.”
When asked if this were a case of the immune system having too little to do and getting itself into trouble, Swirski said, “metaphorically, you could put it that way.”
Possible Applications for Future Medical Treatments
“The body and the brain talk to each other,” said Swirski. “Research now is starting to look at how regions of the brain talk to the immune system and how they may serve as a kind of rheostat, regulating the immune system’s actions so, ideally, it neither overheats nor underperforms.”
Researchers are also discovering that “mental health is not just in your head; it certainly has physical cellular and molecular dimensions.”
Swirski references post-traumatic stress disorder (PTSD) as a prime example of this fact.
“When you examine the history of PTSD, how it was approached in the culture, ideas have changed. It was once thought that someone suffering from it (say a “shell-shocked” war veteran) was just weak: ‘this is just in your head—get yourself together.’ But now we are understanding there are real physiological consequences to the stressors that lead to these conditions—when things enter the domain of rigorous science—the tools that allow you to measure mechanisms at tissue, cellular, and molecular scale.
“Now we have tools that we didn’t have before that allow us to test some of these hypotheses. PTSD has manifestations in the brain—rewiring of the brain architecture, changes in the immune system—in the inflammatory set-point. When you can measure these differences and see statistical differences, you can then start to envision more effective medical interventions while relieving patients of the stigma of blame that previously had been attached.”
Swirski concluded that as we begin to map the biomarkers that communicate between the brain and the immune system, we enhance our ability to design more effective interventions for these conditions.
He cites the example of transcranial magnetic stimulation (TMS), a noninvasive procedure that uses magnetic fields to stimulate nerve cells in the brain to improve symptoms of depression.
“With therapies like this, we may be able to precisely target neural clusters to reprogram or stimulate neurons to do the things we want them to do; change mood, even alter the reward system in the brain so that it’s easier to engage in healthy habits, like getting a good night’s sleep, eating better, and exercising.”
Swirski also said that such research can help us better understand how behavioral choices like meditation or cultivating gratitude or selflessness can have a measurable and significant impact on our brain and body chemistry and thus also reveal the scientific basis for the anecdotal efficacy of these interventions.