Just like we are all capable of far more than we know, we’re learning that our cells do way more than we originally thought. We live in a wonderful scientific age in which long-standing paradigms are being challenged, and one of the most exciting areas of rediscovery (imo) is immunology; we’re finding that immune cells perform functions far beyond classical immunity.
The idea that immune cells are sensitive to how we live is not new. A 1973 article from the Journal of Immunology outlines how cortisol, the hormone most strongly associated with stress, screws up the dialogue among immune cells. More studies than I care to list show that stress makes people more susceptible to disease, disrupts endocrine function, inhibits cognition, worsens cancer progression, and makes life less fun; this field of study is called psychoneuroimmunology (PNI). While I won’t explore PNI here, I wanted to point out that the stress-immune connection goes both ways. Recent work shows that overactive immune systems (sometimes called chronic inflammation), often characterized by an imbalance that favors pro-inflammatory cytokine IL-6, increases cortisol (read: stress) in people. And one more thing about stress; stress leads to increased intestinal permeability (known as ‘leaky gut‘ in the health/fitness internet world) by messing with immune cells. Yikes!
Anyway, immune cells respond not only to stress, but also to how you think, feel, and act. Dopamine, a ‘happy hormone’ that surges when you go on adventures or learn something new, suppresses that harmful chronic inflammation by regulating protein complexes (aptly-named inflammasomes) in several types of immune cells. Oxytocin, the hormone associated with love and connection and induced by hugs and laughter, similarly tamps down rampant inflammation after your immune system fights off bad bacteria. Dopamine also binds directly to antibody-producing B cells, and higher amounts of dopamine-binding on B cells lessens the impact of diseases like rheumatoid arthritis. Serotonin, a feel-good, calming hormone (produced by your microbiota!) induced by sunlight, exercise, and happy thoughts, regulates exocytosis, the cellular process of ‘taking out the trash,’ in brain immune cells (microglia). This regulation is crucial because dysregulated exocytosis leads to buildup of cellular junk in the brain, which has been linked to diseases like Multiple Sclerosis (MS) and Alzheimer’s. I could go on and on, but I think you get the point: immune cells are exquisitely sensitive to the hormones induced by your thoughts, feelings, and actions.
Immune cells also sense nutrient status! First off, chronically elevated leptin levels from being obese or consistently undereating (confusing, but true), and suppresses your immune system. Pathogen defense is an energy-intensive process, and if your body gets starvation signals, it takes a ‘why bother’ approach, and you’ll be more susceptible to infections. So please don’t let your body think it’s starving, either by being deficient in micronutrients or not eating enough!
*hops off soapbox*
Anyway, while a ton of research has shown that immune cells work better when you have enough Vitamin D, Vitamin A, zinc, etc. and that diseases like Type 2 Diabetes are now classified as inflammatory, I want to highlight some of the non-obvious intersections of nutrition and immunity. While we can’t fully characterize the immune effects of nutrition without considering the gut microbiome (the trillions of bacteria, fungi, and other microbes that live inside us and help process our food and train our immune system), I’ll save a comprehensive review of diet and the microbiome for another day 😉
A recent paper from my impressive lab showed that macrophages, commonly thought of as immune surveillance staff, do more than travel through the body looking for threats. These cells also sense the salt concentration inside and outside of cells, and in high-salt environments, macrophages initiate Th17-type inflammatory responses, increase the travel of neutrophils, and induce mitochondria to produce reactive oxygen species (ROS). That is, a high-salt diet can create hyper-inflammatory environments with an abundance of free radicals that lead to DNA damage. Researchers elegantly showed that one of the key consequences of a high-salt diet was dysfunctional mitochondria, which can lead to all sorts of diseases, including rheumatoid arthritis and MS. Additionally, immune cells detect and react to fatty acids, and different chain lengths lead to different responses (see another article I wrote about the dark side of coconut oil). Another interesting example of the intersection of nutrition, metabolism, and immunity is that eosinophils, innate immune cells whose functions are underappreciated imo, interact with white adipose tissue and instruct macrophages to become “alternatively activated”, a state that is associated with cancer. Last but not least, recent studies show that immune cells may be the key orchestrators of fat metabolism; these findings may explain why people reach their desired physique more easily when they focus on health rather than on weight loss.
Based on how we feel and act when we’re sick, it’s not a big leap to understand that immune cells modify our behavior. Abnormally high levels of pro-inflammatory cytokines, triggered when your immune system is fighting threats or enduring stress (including nutrient deficiency!), tell your brain to turn on sickness behavior: lethargy, decreased appetite, joint pain, etc. Additionally, dysregulated immune cells are linked to mood disorders like depression, disrupted sleep and chronic fatigue, and messing up your emotional responses!
An interesting sidebar: a study of male Italian kickboxers showed that those who had higher chronic inflammation (measured by salivary IL-1beta) exhibited more anger…. but the angrier fighters won more matches, so there’s an upside to this hyperimmunity. Furthermore, the angriest fighters showed the highest drop in anger after winning matches, so even if you tend towards anger, hitting the gym (or another kickboxer) can help alleviate some of that aggression. Another way to decrease the aggressive behavior associated with nonspecific inflammation is to eat more tryptophan (which is found in foods beyond turkey!). Tangent completed; back to the subject at hand!
In case you’re not convinced that immune cells do more than just immune things, I’ll tell you that they also:
- sense temperature
- regulate circadian rhythms
- sense and help blunt pain (interestingly, the immune mechanisms of pain perception are different in men and women!)
- modulate blood pressure
- balance electrolytes
- modify gastrointestinal motility
- help rebuild your skeleton