Essentials: Using Your Nervous System to Enhance Your Immune System

**Andrew Huberman** (0:00)
Welcome to Huberman Lab Essentials, where we revisit past episodes for the most potent and actionable science-based tools for mental health, physical health and performance.
I'm Andrew Huberman, and I'm a professor of neurobiology and ophthalmology at Stanford School of Medicine. Today, we are discussing the immune system, and we are also discussing how the nervous system can be used to activate and control the immune system. The first topic we have to attack is the question of what is the immune system and how does it work? I'd like to just take a moment and do a sort of brief immune system 101 Really simple, cover the basic elements of the immune system so that everyone listening or watching this can get a clear sense of how the immune system functions and what its basic parts are. It's actually really simple because it is truly elegant in design. You have three main layers of defense for your health. And the first of those three is a physical barrier that we call your skin. And that might seem kind of obvious, but everything about you is contained in this compartment that is boundaried by your skin. If you've ever had a cut, you essentially have a breach of the boundary that is your immune system. Still in category one, your body and your external surface, you have openings to that surface. So what are those openings? Well, let's start at the top and work our way down. A primary site of potential infection are your eyes, you have your ears, you have your nostrils, you have your mouth. Okay, those are going to be the primary sites by which things can get into your system. And you need to put things into your system. You need to drink and eat, and you need to get light into your system. That's why you have those openings. And then, of course, along the back of your throat, all the way down to your stomach and your digestive system, and through your intestines and out your rectum, you have a tube that you are basically a series of tubes. I've said that before in this podcast, and this is one such tube by which you extract nutrients from the outside environment. But all along that tube, including your nose and your mouth, it's lined with mucus. And while mucus might seem kind of gross to some of you, the more you learn about mucus, the more you realize that mucus is really, really cool. Because mucus essentially acts as a filter, as a trap for bacteria and viruses, and it has certain ways of scrubbing or killing those bacteria and viruses. Now, inevitably, bacteria, viruses and parasitic infections are going to make their way into our body. But whether or not they are killed off, or whether or not they take over and cause us harm, is going to be determined by layers two and three. So layers two and three are the so-called innate immune system and the adaptive immune system. So the innate immune system is what I would call the second layer of defense. It's very fast. So this innate immune system is this rapid response. When something enters our system and our body doesn't recognize it, it's something that's either a bacteria virus or parasite. And the innate immune system involves the release of particular cells that are waiting, dormant, ready to attack whatever this invader is. And some of these cell types you've heard of before, the most typical one are the so-called white blood cells. So the white blood cells will actively go to the site of invasion and will start to encapsulate or try and surround that given invader. The other names of these different cell types are things like neutrophils, macrophages, natural killer cells. There's just a few of the many types of immune cells. They work in concert with two other assistants. And those assistants are called the complement proteins. Compliment proteins exist in the blood. And what they do is they travel to sites where there's an invasion and they mark certain things for being engulfed and eaten. So they sort of put an eat me tag on it. And then there are the cells that are either damaged from the injury or from the parasite or are suffering because of the bacteria or the virus itself. And the cells of your body will also release an alarm signal, which is not an eat me signal, but a help me signal. And those help me signals come in the form, what we call cytokines. And the cytokines are things like interleukin 1, interleukin 6, tumor necrosis factor alpha. The interleukin is shouting out, help me. The complement proteins are coming in and saying, eat this and tagging the invader with an eat me signal. And then the killer cells and the white blood cells are doing the job of trying to kill off that thing. That's the innate immune system. So your skin and your mucus lining, plus your innate immune system are a beautiful, two layered set of defenses against various kinds of invaders and infections. And then there's the third type, which is the adaptive immune system. And you'll notice that leading up until now, I haven't said the word antibody at all. And that's because it is the job, not of the skin or the mucus or the microbiome or the innate immune system to produce antibodies that can recognize specific invaders, but rather it is the job of the adaptive immune system to create antibodies against bacteria, viruses, and even parasites and even physical intruders to your system. So the adaptive immune system has this incredible ability to show up at the site of invasion or infection or inflammation. And what it does is it actually attaches to and creates a sort of an imprint of the shape of whatever invader happens to be there. And then using that imprint, in concert with some other cells, creates antibodies that are specific to recognize that invader should the body ever have that invader inside of it again. Now, that's why it's called the adaptive immune system. And in many ways, it creates a memory of a prior infection so that these antibodies can be made any time that same invader comes back again, all right? And so this is the basis of what we call immunity. Now, there are a lot more details to the adaptive immune system, but I just want to emphasize a few points that might be relevant. First of all, the name of the antibodies that are created sometimes come in the form of IgM and IgG, things of that sort. This isn't a full deep dive immunology class, but Ig stands for immunoglobulin, okay? So the immunoglobulins are part of the adaptive immune response in creating antibodies. If you hear IgM, the IgM is the first of the adaptive immune responses, and it tends to come on earlier. So if somebody is immunopositive for IgM for a particular type of viral or bacterial invader, that means that it was a fairly recent infection. Later, one creates the adaptive immune system, I should say creates an IgG, which is the more stable form of the specific antibody that's going to recognize a given invader. So IgG tends to come up a little bit later. So just to recap, something gets into your system. Then there's the innate response, which is a more general response of trying to contain and combat the infection or invader. And then the adaptive response is the one that generates the antibodies first, the IgM response, the immunoglobulin M response, and then the immunoglobulin G response, IgG response. So how do we keep these three barriers or these three defense systems to infection tuned up? One of the key ways we can do that is to keep that mucus lining in really good shape. And what does that mean? Well, the mucus lining needs to turn over quite often, and it needs to be the correct chemistry to be a trap for the bad stuff and for it to be permeable to the good stuff, to the nutrients that we need. And it is now very clear from hundreds, if not thousands of studies, that the best way to do that is to maintain a healthy so-called microbiome. The microbiome being these little bacterial organisms that are good for us that live all along our mucus pathways and even in our eyes. Now, just to be really clear, it's not just about the gut microbiome. We actually have a microbiome in our eyes. We have one that's specific to our mouth. We have a nasal specific microbiome. There's one all along the gut and the species of microbiota that live all along the digestive tract differ from the mouth to the throat, to the stomach, intestines and to the rectum. It's well established that there are healthy microbiota that live all along that length and they differ along that length. This is a reminder that whenever possible, unless eating or speaking, you want to be nasal breathing, not breathing through your mouth. Your nose is a much better filter for viruses and bacteria than is your mouth. And so be a nose breather, not a mouth breather. You will combat more of the infections that you are constantly confronted with. The other way to try and keep out bad things and to avoid getting sick is the advice that your mother and certainly my mother gave me, which is to not touch your eyes after touching other people or touching other surfaces. And the reason to avoid doing that is the eyes are a primary entry point for a lot of bacteria and viruses. And then the third way to keep a healthy line of defense for your entire mucus tract is to enhance the proliferation of good gut microbiota. The best way to enhance the quality of your gut microbiome and the mucus lining that serves as this protective layer all along your body is to ingest two to four servings a day of fermented foods, low sugar fermented foods. It helps reduce the activity of certain cytokines. When people have a healthy gut microbiome, there are fewer cells in the body being infected from outside infections and therefore less of a reason for cells to be crying out help because they are thriving, not suffering. Things like sauerkraut, things like natto, if you can access that, kimchi, pickles, again, low sugar sources are going to be the sources that are going to be most effective for this. I'd like to take a quick break and acknowledge our sponsor, AG1. By now, many of you have heard me say that if I could take just one supplement, that supplement would be AG1. The reason for that is AG1 is the highest quality and most complete of the foundational nutritional supplements available. What that means is that it contains not just vitamins and minerals, but also probiotics, prebiotics and adaptogens to cover any gaps you may have in your diet and provide support for a demanding life. For me, even if I eat mostly whole foods and minimally processed foods, which I do for most of my food intake, it's very difficult for me to get enough fruits and vegetables, vitamins and minerals, micronutrients and adaptogens from food alone. For that reason, I've been taking AG1 daily since 2012 Well, when I do that, it clearly bolsters my energy, my immune system and my gut microbiome. These are all critical to brain function, mood, physical performance and much more. If you'd like to try AG1, you can go to drinkag1.com/huberman to claim their special offer. Right now, they're giving away five free travel packs plus a year supply of vitamin D3 K2. Again, that's drinkag1.com/huberman to claim that special offer. Next I'd like to talk about what's called sickness behavior. Sickness behavior is a suite of responses that we tend to all undergo when we are feeling sick. The main thing about sickness behavior is that it tends to involve a slowing of our usual levels of activity. People start to feel lethargic or they feel like the activities that previously they could do with relative ease are very difficult for them or somewhat overwhelming. The other thing you start to see is that people and animals, by the way, stop grooming. They stop taking care of themselves. Not necessarily stop showering, although oftentimes that's the case, but they will stop doing their hair. They'll stop putting on makeup, you know, depending on whether or not they did that before, they might stop. Animals will stop licking and grooming themselves. People will stop taking care of their cosmetic appearance. Now, it's not just because they don't care how they look when they're sick. It's because there's this overall suppression of certain kinds of activities and an enhancement of other kinds of activities. And this is really important. Sickness behavior is actually a motivated state. It's a state that's designed to accomplish certain things. One of the other features of sickness behavior, in addition to being lethargic, loss of grooming, will be a loss of appetite, right? Oftentimes people who have a great appetite normally just won't feel hungry at all. When we have that, we can be kind of irritable. We don't want to do certain things and we just want to be left alone. Things are harder. How? Why? Well, there's a known pathway, which is the so-called vagus nerve that connects the body and the brain, signals to particular brain sites to engage this category of motivational state that we call sickness behavior. The vagus nerve is a very extensive nerve pathway. It's the 10th cranial nerve comes out of the back of the brain stem, heads into the body, and branches out extensively to innervate or connect to many of our organs, including our lungs, our heart, our gut, et cetera. And all of those organs are able also to send neural signals back up to the brain. We sometimes hear the vagus as the route to calming ourselves down. Unfortunately, that's more or less a myth that I don't know how it got propagated. There have now been many studies of the vagus in various contexts, including in sickness behavior. And it's very clear that the vagus nerve is the fast pathway by which an infection in the body is signaled to the brain, to a particular location in the brain called the hypothalamus, which harbors a lot of different types of neurons. Neurons, for instance, in the preoptic area that increase body temperature and fever, right? That's one of the most important things is to increase body temperature in order to... It's the body's attempt to kill off this invader because many viruses and many bacteria don't survive well at elevated heat. That's the function of a fever. It also sends input to areas of the brain that change your perception of the outside world. One of the most obvious of these, obvious once I tell it to you, is photophobia, right? I love bright sunshine. I love bright lights when I want to be alert. But most people, when they are sick, when there's an inflammation response in the body, they feel like bright lights are kind of aversive. They get a well-described kind of classical photophobia. And that's mediated by a pathway that goes from your eye to an area of your thalamus, called the anterior nucleus of the thalamus. Then from there up to the outer lining of the brain, which is the meninges, just sort of on the outside of the brain, where the brain starts to interface with some of the other connective tissues. It can actually create a photophobia and a headache when one is ill. And the last element I'd like to talk about is the rest. There's something that gets triggered from the body to the brain, to the hypothalamus, and there are nuclei there that promote the desire to sleep even during the daytime, what would normally be the active phase of your circadian cycle. Now that is really interesting because what's happening here is you've got multiple pathways that are saying avoid light, reduce your amount of behavior, heat up all the things that are making you sick. This is sickness behavior and it's going from your body to your mind to make you do the right thing. Now there's also a slow pathway that's purely mediated by the blood, so-called humoral factors, not because they're funny, but humoral factors are factors of the blood. As you have an infection for many hours or days, the amount of IL-6 and IL-1 and tumor necrosis factor and other inflammatory cytokines is starting to increase such that the total amount in your circulation gets high enough and is communicated to the brain. And it tends to enter the brain through a particular type of tissue that's really interesting called choroid, C-H-O-R-O-I-D.