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Huberman Lab

Essentials: Using Your Nervous System to Enhance Your Immune System

Published September 25, 2025
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About This Episode

Andrew Huberman explains how the immune system works, outlining the three main defense layers: physical barriers like skin and mucus, the innate immune response, and the adaptive immune system that generates antibodies. He describes how sickness behavior arises via neural and blood-borne signals, then details specific nervous-system-based tools-sleep posture, a cyclic hyperventilation breathing protocol, mindset effects on dopamine, fascia-targeted electroacupuncture, and spirulina-that can reduce inflammation, support immune function, and potentially shorten illness duration.

Topics Covered

Immune system Immune system and cytokine storms Autonomic nervous system Breathwork Respiration Glymphatic system Lymphatic system Stress management Inflammation and CRP Brain health

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Quick Takeaways

  • The body defends itself through three main layers: physical barriers (skin and mucus), a fast-acting innate immune response, and a slower adaptive immune system that builds long-term immunity via antibodies.
  • A healthy microbiome and mucus lining-supported by nasal breathing and 2-4 daily servings of low-sugar fermented foods-are crucial for filtering pathogens and reducing unnecessary inflammatory signaling.
  • Sickness behavior (fatigue, social withdrawal, loss of appetite, photophobia, and increased need for sleep) is a deliberately orchestrated brain-body state triggered via the vagus nerve and circulating cytokines.
  • Elevating the feet during sleep by roughly 12 degrees can enhance glymphatic clearance in the brain, which becomes especially important during infections to remove inflammatory debris.
  • A specific cyclic hyperventilation plus breath-hold protocol can acutely increase epinephrine, reduce pro-inflammatory cytokines, increase anti-inflammatory cytokines, and lessen flu-like symptoms after an immune challenge.
  • Short-term stress responses driven by catecholamines like epinephrine can temporarily enhance immune function, explaining why people often get sick only after a stressful period ends.
  • Activation of dopamine-based reward pathways linked to a sense of future and hope can measurably improve outcomes in cancer, wound healing, and recovery from illness by shifting inflammatory cytokine balance.
  • Electroacupuncture targeting deep fascial neurons in the limbs can drive a vagal-adrenal reflex that releases catecholamines and lowers inflammation, via a mapped neural circuit from fascia to adrenal glands.
  • Typical decongestant drugs reduce nasal inflammation via epinephrine pathways but can cause dehydration and disrupt sleep, whereas spirulina at around 2 grams per day has been shown in humans to improve rhinitis symptoms and reduce inflammatory markers.

Podcast Notes

Introduction and framing of nervous system-immune system interaction

Show introduction and host credentials

Huberman Lab Essentials revisits past episodes for potent science-based tools[0:04]
• Focus is on practical tools for mental health, physical health, and performance, drawn from prior Huberman Lab content
Host and topic[0:26]
• Andrew Huberman introduces himself as a professor of neurobiology and ophthalmology at Stanford School of Medicine
• States that the episode will discuss the immune system and how the nervous system can be used to activate and control it

Goal: Immune system 101 overview

Purpose of the basic review[0:39]
• He aims to give a simple, clear explanation of how the immune system functions and its basic parts so listeners can follow later tools
Three main layers of defense[0:56]
• Describes the immune system as having three main defense layers, starting with physical barriers and progressing to cellular and adaptive mechanisms

Physical barriers: Skin, openings, and mucus

Skin as the first barrier

Skin as a compartment boundary[1:06]
• Everything about you is contained in a compartment bounded by your skin, which serves as the first layer of immune defense
• A cut is described as a breach of this boundary, giving invaders direct access past the first defense layer

Body openings as potential infection sites

Primary entry sites[1:42]
• Lists eyes, ears, nostrils, and mouth as primary sites where things can enter the body
• These openings are necessary to bring in light, food, and drink, but they also create vulnerability to infection
Digestive tract as a tube open to the outside[1:51]
• Describes the pathway from the back of the throat down to the stomach, through intestines, and out the rectum as a continuous tube
• Emphasizes that we are in many ways "a series of tubes" through which nutrients are extracted from the outside world

Mucus linings and their role

Mucus as a filter and trap[2:24]
• Notes that the nose, mouth, and the entire digestive tube are lined with mucus
• Explains that mucus acts as a filter and trap for bacteria and viruses and can scrub or kill them
Limitations of physical barriers[2:45]
• Acknowledges that despite mucus and skin, bacteria, viruses, and parasites inevitably enter the body
• States that whether these invaders are killed off or cause harm depends on the second and third immune layers

Innate immune system: Rapid generalized defense

Overview of innate immunity

Innate immune system as second defense layer[3:05]
• Describes the innate immune system as a very fast, rapid-response system that reacts when an unrecognized bacterium, virus, or parasite enters

Key innate immune cells

White blood cells and other cell types[3:31]
• Mentions white blood cells as the most typical innate immune cells that travel to the site of invasion and try to encapsulate the invader
• Names additional innate cells: neutrophils, macrophages, and natural killer cells as part of the response

Complement proteins and cytokines

Complement proteins as "eat me" taggers[4:01]
• Explains that complement proteins in the blood travel to invasion sites and tag invaders with an "eat me" signal so immune cells engulf them
Cytokines as "help me" signals[4:35]
• Describes how damaged or stressed cells release alarm signals in the form of cytokines, which are "help me" signals rather than "eat me" tags
• Lists cytokines such as interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α) as examples
Coordinated innate response[4:57]
• Summarizes that complement proteins mark invaders, cytokines broadcast distress, and killer/white blood cells physically attack the invader
• Frames skin, mucus lining, and innate immune system as a two-layered defensive set against infections

Adaptive immune system and antibody-based memory

Adaptive immunity overview

Role of adaptive immune system[5:15]
• Clarifies that up to this point he has not mentioned antibodies because their production is the job of the adaptive, not innate, immune system
• States that the adaptive system creates antibodies against bacteria, viruses, parasites, and even physical intruders

Mechanism of antigen recognition and memory

Imprinting invaders and generating antibodies[5:37]
• Explains that adaptive immune components show up at infection or inflammation sites and attach to invaders to create an imprint of their shape
• Using this imprint plus other cells, the system produces antibodies specifically tailored to recognize that invader in the future
Immunity as adaptive memory[6:19]
• Notes that the adaptive system effectively creates a memory of prior infection so antibodies can be rapidly produced when the invader reappears

IgM and IgG antibodies

Immunoglobulins and timing of response[7:02]
• Introduces antibody classes like IgM and IgG, explaining that IgG stands for immunoglobulin G and is part of adaptive responses
• States that IgM tends to be the first adaptive response and appears earlier in infection, indicating a recent infection when present
• Explains that IgG appears later as a more stable, specific antibody form that recognizes a given invader over time

Recap of three-stage immune response

Sequence from invasion to adaptive memory[7:28]
• Recaps that after something enters the system, the innate response provides general containment and combat, followed by adaptive antibody generation
• Describes the progression from IgM to longer-lasting IgG antibodies as the infection course unfolds

Maintaining mucus linings and microbiome health

Importance of mucus lining turnover and chemistry

Optimal mucus function[8:13]
• Mucus must turnover frequently and maintain the right chemistry to trap harmful agents while remaining permeable to essential nutrients

Microbiome as key to barrier health

Microbiome across multiple body sites[8:37]
• States it is clear from hundreds or thousands of studies that maintaining a healthy microbiome is the best way to keep the mucus lining healthy
• Emphasizes that microbiomes exist not just in the gut, but also in the eyes, mouth, and nasal passages
• Notes that microbial species differ along the digestive tract from mouth to throat, stomach, intestines, and rectum

Nasal breathing versus mouth breathing

Nose as superior filter[9:26]
• Advises that whenever possible, except while eating or speaking, one should breathe through the nose rather than the mouth
• States that the nose is a much better filter for viruses and bacteria than the mouth, and nasal breathing will help combat more infections

Avoiding contamination via eyes

Hand-to-eye transmission risk[9:44]
• Repeats conventional advice not to touch your eyes after contacting other people or surfaces because eyes are a primary entry point for pathogens

Using diet to support microbiome and mucus

Fermented foods as microbiome support[10:28]
• States that the best way to enhance gut microbiome quality and protective mucus lining is to ingest two to four servings per day of low-sugar fermented foods
• Mentions examples such as sauerkraut, natto, kimchi, and pickles, specifying that low-sugar versions are most effective
Effect on inflammatory cytokines and cell health[10:34]
• Says a healthy gut microbiome reduces activity of certain cytokines and results in fewer cells being infected by external agents
• Explains that with fewer infections, cells have less reason to send "help" signals and instead are more likely to thrive

Sickness behavior and brain-body signaling pathways

Definition and features of sickness behavior

Core symptoms of sickness behavior[12:15]
• Defines sickness behavior as a suite of responses, including slowing of activity, lethargy, and finding usual tasks overwhelming
• Includes reduced grooming and self-care: people may stop doing hair, makeup, or showering; animals stop licking and grooming
• Notes loss of appetite and a desire to be left alone; people can become irritable and find normal activities too difficult
Sickness behavior as a motivated state[13:08]
• Emphasizes that sickness behavior is not random but a motivated state designed to accomplish certain biological goals

Fast neural pathway: vagus nerve signaling

Role and anatomy of the vagus nerve[13:41]
• Describes the vagus as the 10th cranial nerve, emerging from the brainstem and innervating organs like lungs, heart, and gut
• Clarifies that organs innervated by the vagus also send signals back to the brain
Myth about vagus and calming[14:21]
• Notes that popular claims that the vagus is simply a route to calm ourselves are largely a myth unsupported by current data
Vagus as a fast infection signal to brain[14:43]
• States that the vagus is the fast pathway by which body infections are signaled to the brain, especially the hypothalamus
• Mentions hypothalamic neurons in the preoptic area that increase body temperature, producing fever to help kill invaders

Changes in sensory processing and sleep

Photophobia and headache mechanism[15:59]
• Observes that when sick, people often experience photophobia, finding bright light aversive, unlike when healthy
• Explains that this is mediated by a pathway from the eye to the anterior nucleus of the thalamus and then to meninges at the brain surface, creating photophobia and headache
Rest and daytime sleep drive[16:03]
• Describes brain nuclei in the hypothalamus that, when activated by body-brain signals, promote a strong desire to sleep even during the usual active circadian phase
• Summarizes that multiple signals converge to encourage reduced movement, light avoidance, and increased rest to support recovery

Slow humoral pathway: cytokines and brain inflammation

Accumulation of inflammatory cytokines in blood[17:03]
• Over hours or days of infection, levels of IL-6, IL-1, TNF-α, and other cytokines rise in circulation
Choroid and brain entry[17:11]
• Explains that cytokines influence the brain via a tissue called the choroid, which responds to and releases inflammatory signals
Cognitive and mood effects of brain inflammation[17:32]
• Describes how inflammation in the brain leads to poor memory, impaired cognition, and inability to engage with reading or movies
• Notes that when someone is so sick they "can't be bothered by anything," this reflects both fast and slow inflammatory signaling reaching the brain

Leveraging the nervous system to enhance immune function

Reversing the usual body-to-brain sickness signaling

Question posed: can brain drive immune enhancement?[18:05]
• Proposes flipping the equation: instead of body triggering brain sickness behavior, use the nervous system to enhance immune function and speed recovery
Standard advice: hydration and sleep[18:59]
• Acknowledges common guidance to hydrate and get 9-10 hours of sleep when sick
• States that beyond this, there are active strategies to deploy a more robust early immune response

Glymphatic system and sleep posture

Glymphatic system function[19:44]
• Describes the glymphatic system as a brain system that clears debris accumulated during the day and especially under neuroinflammatory conditions
• Notes that glymphatic activity is much higher during sleep, particularly early in the course of viral or bacterial infections
Enhancing glymphatic flow by elevating feet[20:10]
• Explains that due to glymphatic mechanics, elevating the heels by about 12 degrees during sleep enhances glymphatic clearance
• Suggests placing a rolled pillow or two pillows under the feet so the head is below the legs while sleeping when not feeling well
• Mentions this posture might also be useful during short daytime naps if someone must remain awake but wants to support clearance

Cyclic hyperventilation breathing protocol and immune response

Overview of PNAS study on voluntary sympathetic activation

Study title and journal[22:43]
• Cites a paper titled "Voluntary Activation of the Sympathetic Nervous System and Attenuation of the Innate Immune Response in Humans" published in PNAS
Sympathetic nervous system definition[23:05]
• Defines the sympathetic nervous system as a division of the nervous system involving neurons in the brain and spinal cord that increase arousal and alertness
• Associates it with epinephrine release in the brain and adrenaline release in the body, constituting the fight-or-flight system when highly active

Study design: E. coli injection and breathing intervention

Experimental manipulation[24:02]
• Describes that subjects were injected with E. coli bacteria, which reliably makes people feel very ill
• One group performed a cyclic hyperventilation plus retention breathing protocol; the control group did a basic meditation
Main findings on cytokines and symptoms[24:38]
• Reports that in the breathing group, plasma levels of anti-inflammatory cytokine IL-10 increased after endotoxin administration
• Notes that this IL-10 increase was triggered by increased epinephrine/adrenaline
• States that levels of pro-inflammatory TNF-α, IL-6, and IL-8 were lower in the breathing group than in controls
• Mentions that flu-like symptoms were also reduced in the breathing intervention group

Description of cyclic hyperventilation (Wim Hof-like) protocol

Structure of the breathing pattern[25:27]
• Explains that the protocol involves 20-30 deep inhales and exhales through the mouth followed by a full exhale and breath hold (retention)
• After holding with lungs empty for roughly 15-60 seconds, the 25-30 breath cycle is repeated for a total of about three rounds
Physiological effect during practice[26:05]
• Mentions that doing 30 breaths causes noticeable heating and perspiration, indicative of adrenaline release from this breathing pattern

Mechanisms: catecholamines, stress, and immune modulation

How breathing shifts inflammatory profiles

Epinephrine as key mediator[26:31]
• States that the mechanism is beyond the scope of full detail but centers on epinephrine/adrenaline release reducing inflammation
• Connects this to common experience of powering through stress without getting sick until after the stressful period ends
Shared stress and infection-combat system[26:08]
• Argues that psychological stress and combating infection or wounds share the same stress system rather than being separate systems
• Notes that high levels of epinephrine and adrenaline under short-term stress actually improve the ability to combat infections and reduce inflammation

Practical use and caveats of the breathing tool

Huberman's personal application[27:57]
• He reports using this breathing pattern whenever he senses early signs of illness, such as a tickle in his throat or nasal sensations suggesting a bug
• Says he has used it consistently for more than four years and finds that early symptoms often disappear or he can push through longer
Warnings about overuse and contagion[28:32]
• Advises against using the breathing protocol simply to continue pushing through heavy exposure or contagious illness, due to risk of crashing and infecting others
Zero-cost behavioral tool bridging systems[29:35]
• Highlights this breathing protocol as a clear, zero-cost behavioral tool that connects nervous system activation to the immune system via catecholamines
• Emphasizes that it reduces the negative feelings of an induced E. coli infection in the studied subjects

Dopamine, motivation, and immune outcomes

Catecholamine measurements in breathing study

Changes in epinephrine, norepinephrine, and dopamine[31:20]
• Reports that in the breathing group, epinephrine showed robust increases compared to controls
• Notes that norepinephrine increased significantly but less dramatically, while dopamine levels actually dropped somewhat

ISA Rolls lab: hope and immune function

Hope and better clinical outcomes[32:41]
• Cites a literature showing that cancer patients or individuals with severe injuries who report a sense of hope experience higher recovery rates
Dopamine and future-oriented mindset[31:57]
• Defines a sense of hope as a sense of the future, which is tightly linked to the dopamine system
• Explains that activating the mesolimbic reward pathway-associated with thinking about a (ideally positive) future-can reduce tumor size, speed wound healing, and hasten illness recovery
• States that this reward pathway activation lowers inflammatory cytokines and increases anti-inflammatory cytokines
Connection to breathing-induced catecholamine shifts[31:51]
• Draws a parallel between dopamine/catecholamine-modulated improvements in immune function and the catecholamine changes seen in cyclic hyperventilation studies

Electroacupuncture, fascia, and the vagal-adrenal axis

Overview of Ma lab electroacupuncture study

Study title and objective[34:10]
• Mentions a paper titled "A neuroanatomical basis for electroacupuncture to drive the vagal adrenal axis" from Chufu Ma's lab at Harvard Medical School

Body sites and inflammatory effects

Differential effects by stimulation location[34:18]
• Explains that electroacupuncture at certain body sites, such as the abdomen, increases inflammation via inflammatory cytokine release
• States that stimulating lower or hind limb sites can instead drive the vagal-adrenal reflex and reduce inflammation

Fascial neurons and neural pathway mapping

Neurons in fascia as key sensors[35:04]
• Reports that Ma's lab identified specific neurons located in the fascia, the thick sheath surrounding muscle, that respond to electroacupuncture
• Names these neurons as PROK R2 (PROKR2) neurons, though he notes the exact name is less important than their function
Circuit from fascia to adrenal gland[35:43]
• Describes that PROKR2 neurons send projections into the spinal cord, then to a region in the hindbrain called the medulla oblongata
• From the medulla, downstream pathways connect to the adrenal gland to trigger release of norepinephrine, epinephrine, and dopamine
Outcome: catecholamine release and inflammation reduction[36:19]
• Summarizes that activating deep fascial tissue with electroacupuncture causes catecholamine release, which in turn lowers inflammation
• Highlights the similarity to the breathing protocol, where catecholamine release also leads to anti-inflammatory effects

Managing symptoms once sick: drugs and spirulina

Conventional decongestants and limitations

Mechanism of common over-the-counter medications[36:42]
• Notes that many over-the-counter medications for congestion work via the epinephrine system, similar to pseudoephedrine-like compounds
• Says these agents reduce congestion by promoting epinephrine release that dilates bronchioles and nasal passages
Drawbacks: dehydration and sleep disruption[37:17]
• Warns that such medications can cause dehydration, making proper fluid and electrolyte intake essential if they are used
• Adds that they often interfere with sleep, which is counterproductive to recovery

Spirulina as an alternative for rhinitis

Nature of spirulina and study designs[37:32]
• Describes spirulina as a form of algae with data supporting its use for reducing rhinitis (nasal inflammation and congestion)
• Mentions human randomized, double-blind trials, including one with 129 subjects and another with 65 subjects
Dose and observed benefits[38:03]
• Reports that taking 2 grams (not milligrams) of spirulina led to significant decreases in nasal obstruction and improved ability to smell
• States that participants experienced improved sleep, reductions in inflammatory cytokines, and less nasal itching

Recap of key concepts and protocols

Summary of immune and nervous system interactions

Three immune components and their neural links[38:35]
• Recaps the adaptive and innate immune systems and their interaction with the nervous system throughout the episode

Summary of protocols for illness prevention and recovery

Behavioral tools discussed[38:41]
• Highlights nasal breathing, fermented foods for microbiome health, elevating feet during sleep for glymphatic clearance, cyclic hyperventilation breathing, hope/positive future thinking, fascia-targeted stimulation, and spirulina as tools to avoid or shorten illnesses and inflammation

Lessons Learned

Actionable insights and wisdom you can apply to your business, career, and personal life.

1

Your first line of immune defense-skin, mucus, and microbiome-is highly modifiable through daily habits like nasal breathing and regular intake of low-sugar fermented foods.

Reflection Questions:

  • • What specific changes can you make this week to prioritize nasal breathing over mouth breathing in your daily life?
  • • How could you realistically incorporate two to four servings of low-sugar fermented foods into your regular diet?
  • • In what environments or routines (e.g., commuting, working, exercising) are you most likely to compromise your barriers, and how can you protect them more intentionally?
2

Sleep is not just rest; positioning your body to support brain glymphatic clearance can actively accelerate recovery from infections and inflammation.

Reflection Questions:

  • • When you are sick or run down, how often do you intentionally modify your sleep setup rather than just sleeping more?
  • • How might elevating your feet by roughly 12 degrees during sleep change the way you feel after a night of rest during illness?
  • • What practical adjustments (pillows, bed wedges, nap positions) can you set up in advance so that you automatically support glymphatic clearance when you start to feel unwell?
3

Deliberately activating the sympathetic nervous system through structured breathing can acutely shift your cytokine profile, making stress a tool rather than just a liability when used briefly and strategically.

Reflection Questions:

  • • In what early-warning situations (scratchy throat, fatigue, known exposure) could you test a few rounds of cyclic hyperventilation as an experiment?
  • • How can you distinguish between using short, intentional stressors like this breathing protocol versus chronically pushing yourself and risking a bigger crash?
  • • What boundaries will you set (time of day, number of rounds, health conditions) to ensure you use such breathing as a targeted intervention rather than a default coping mechanism?
4

Your mindset about the future-especially cultivating a realistic sense of hope-can measurably alter immune function via dopamine pathways, making psychological tools biologically consequential.

Reflection Questions:

  • • When you face a health or performance setback, what stories do you tell yourself about the future, and do they increase or decrease your sense of agency?
  • • How might deliberately visualizing a concrete, positive future outcome before sleep or during illness change your motivation to follow through on supportive behaviors?
  • • What simple daily practice (journaling, brief future visualization, conversations) could you adopt to consistently activate a hopeful, future-oriented state?
5

Body-based interventions that target neural circuits-through breathing, posture, or specific sensory stimulation-can modulate catecholamines and inflammation just as powerfully as many drugs, but with different side-effect profiles.

Reflection Questions:

  • • Where in your current routine do you default to pharmacological solutions first, and could a safe body-based intervention reasonably be tried beforehand?
  • • How could you build a small personal "protocol menu" (e.g., breathing, posture changes, light exposure, gentle stimulation) for times when you feel early signs of illness or inflammation?
  • • What criteria will you use to decide when a body-based approach is sufficient and when you should instead (or also) seek medical evaluation and medication?

Episode Summary - Notes by Cameron

Essentials: Using Your Nervous System to Enhance Your Immune System
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