Immune System

The immune system is so fascinating and complicated. I have done my best to describe it in a way that is comprehensible, interesting and relevant to autoimmune recovery. Hopefully you will get to the end of this page with a feeling of awe, a renewed appreciation for your body, and many more questions about how you can support your body in the process of repair and recovery.

The role of the Immune System

The immune system isn’t just your defence force; it’s your body’s sensor and repair network. Every second it decides what belongs, what doesn’t, and what needs fixing. It patrols every tissue, clearing debris, patching damage, and learning from experience.

Its role is to exert force appropriately — to be fierce when needed and otherwise calm. It recognises you and keeps peace with the trillions of microbes that live alongside you. It knows when to respond and when to stand down. Autoimmunity is a disruption in that balance — when defense and repair lose coordination. But the same mechanisms that go wrong are also the ones that can be restored: recognition, tolerance, communication, and calm.

Where is the Immune System

The immune system is a network of cells woven through nearly every tissue of the body. There are dedicated immune organs - the bone marrow (where immune cells are born) and the thymus (where new T-cells are educated) and peripheral immune organs (such as lymph nodes). Immune cells travel through the blood vessels and lymphatic vessels, and the lymph nodes along the way that act like border stations, where immune cells sample what's passing by and decide how to act.

There are local branches of the immune system throughout the body. Each tissue has its own little army tuned to its environment. The spleen filters blood and mounts systemic immune responses. The liver is packed with Kupffer cells that clear pathogens, debris, endotoxin and immune complexes. The lungs are full of alveolar macrophages that scan inhaled air. The skin is patrolled by Langerhans cells and resident T-cells. The brain is protected by microglia, the nervous system's built-in immune cells. Over half of the body’s immune cells live in or around the intestine, in structures called gut-associated lymphoid tissue (GALT). The immune cells of the GALT sit just beneath the lining of the gut, deciding what counts as friend (food, microbiota) and what is foe (pathogens). Every meal, every breath, every swallowed microbe is an education. When the gut barrier is intact and the microbiome balanced, this education produces tolerance: immune cells learn to coexist peacefully with food antigens, commensal microbes, and self-tissues. This is why gut health and immune balance are inseparable.

Everywhere outside of the dedicated immune organs is called the 'periphery' - the everyday environment of the body, where the cells of the immune system are busy patrolling and working to attack invaders and maintain balance. Immune cells work to neutralise threats and they also release chemical messages such as cytokines and interact with hormonal and neural signals. In this way, immunity is both a cellular army and a signalling language.

Key concepts

The periphery in immunology terms is everywhere outside of the bone marrow and thymus.

Barrier cells are the body’s first line of defence — literal physical frontiers that stop your body being inhabited by things that aren't you. They include the skin, the gut lining, the airway, the blood-brain-barrier, and the mucosal surfaces of your eyes, lungs, urinary and reproductive tracts. Barrier cells don’t just form a wall, they actively patrol it: producing antimicrobial peptides, mucus traps, and chemical signals, while quietly sampling the environment to tell the immune system what’s normal and what’s not. They’re less like a brick wall and more like a smart border crossing with sensors, surveillance, customs officers, and emergency alarms — most days calmly filtering traffic, but fully capable of shutting everything down when necessary.

The immune milieu (French for environment) is the chemical and signalling environment in which the cells of the immune system operate. We can think of it as the climate of an immune area. Each immune area (tissue of the body) has its own rules, tone and cytokine climate. And at any time, that milieu can be inflammatory or tolerant.

Inflammation is rapid-response defense state which is activated when the body senses threat or damage. It’s not a mistake — it’s a tactic: heat, swelling, redness, pain and chemical alarms are the immune system’s version of moving civilians out, locking the borders, and deploying emergency services.

Tolerance is the immune system’s ability to recognize something and not attack it — especially your own tissues, food, friendly microbes, and babies in the womb. Tolerance is peacekeeping, diplomacy, rebuilding, restraint. Without it, your immune system would be like a country that declares war on its own citizens.

Immune regulation is the process that drives the system from inflammation to tolerance.

Key players

Dendritic cells are the body's biological researchers covering in long sampling arms called dendrites. They collect samples and display them to T-cells in the lymph nodes, including a message to inform the T-cells whether those samples were collected in peace-time (tolerant milieu) or war-time (inflammatory milieu). This message directs the T-cells toward attack, tolerance, or regulation, depending on the information provided. This means that the dendritic cell researchers are the difference between “mobilize the troops” and “nothing to see here.”

B-cells are born and tested in the bone marrow and enter circulation as naïve B-cells, each with a single unique receptor on its surface — a random “key” that might match one possible antigen someday. Most of their life they circulate as naïve B cells, waiting for something that fits their receptor. When one does encounter its matching antigen and receives the right guidance signals (mainly from helper T cells), it gets activated. Then it can become a plasma cell that produces antibodies, which bind to pathogens to neutralise them and mark them for removal. Or it can become a memory B-cell, ready to activate if the antigen returns.

T-cells are born in the bone marrow and educated in the thymus, then enter circulation as naïve T cells, each carrying a single unique receptor generated at random that can recognise one specific antigen. Most spend their lives quietly patrolling the body, waiting for their one molecular match. When a naïve T-cell encounters its matching antigen being displayed by a dendritic cell — and the dendritic cell signals that it was found in a context of danger — the T cell becomes activated. An activated T-cell can become a cytotoxic T-cell (to kill infected or malfunctioning cells), a helper T-cell (coordinating other immune cells), a regulatory T-cell (peacekeeper) or a memory T-cell (a veteran). T-cells do not make antibodies. Their power lies in directing the immune response, eliminating compromised cells, and keeping the system balanced between action and restraint.

Regulatory B-cells release calming signals like IL-10 to slow inflammation and support tolerance.

Regulatory T-cells act as immune brakes, calming inflammation, protecting healthy tissue, and maintaining tolerance to self.

Healthy function of the Immune System

A healthy immune system should be calm and tolerant until there is a real threat, when it mobilises an appropriate response. As an example, let's look at how the immune system responds to infection. A virus enters through the nose. Within hours, it reaches cells lining the airway and begins replicating. Infected cells know their fate early and send out alarms—interferons, the distress signal that says: “I’ve been compromised.”

At the periphery, resident macrophages and dendritic cells collect viral debris and broadcast inflammatory cytokines—not panic, just triage. The nervous system hears first. Sensory nerves detect inflammatory signals and tell the brain within milliseconds. The brain’s response centre (hypothalamus) signals to the endocrine system. The pituitary releases ACTH (Adrenocorticotropic hormone), and the adrenals release a pulse of cortisol. Blood flow increases, immune cells mobilise, and there forms a controlled antiviral milieu which is less hospitable to viral replication, more activating to immune cells. Dendritic cells present viral fragments to naïve T-cells. Cytotoxic T-cells deploy to infected tissue. Helper T-cells support B-cells to make targeted antibodies. The brain supports this state too—sleep pressure increases, metabolism shifts, behaviour changes (rest, withdrawal, warmth-seeking), all orchestrated via neuroimmune signalling.

Cytotoxic T-cells deploy to hunt infected cells, recognising viral signatures displayed like distress flags (MHC I). They eliminate infected cells cleanly, preventing the virus from multiplying.

Helper T-cells release guidance signals, pushing the right B-cells to mature into plasma cells, producing antiviral antibodies. These antibodies bind viral particles, blocking them from infecting more cells and marking them for removal.

As viral levels fall, the crucial counterbalance emerges. Tregs and Bregs release calming cytokines, downshift inflammation, limit immune reactions, prevent unnecessary tissue damage, and maintain tolerance to the body’s own cells.

After a threat is neutralised, most immune cells involved in the battle undergo programmed cell death (apoptosis), allowing tissues to reset. A small population of memory T-cells and B-cells remain so the next encounter will be faster, lighter, smarter. Macrophages change from destructive M1 mode to restorative M2 mode, clearing debris and promoting tissue healing. Tregs release anti-inflammatory cytokines like IL-10 and TGF-β to quiet the system. Fibroblasts rebuild structure, stem cells regenerate tissue, and the whole network returns to baseline readiness.

This carefully orchestrated response ensures that inflammation begins when needed, reaches an appropriate peak, and then resolves. When this communication is clear, immune responses are targeted, proportionate, and time-limited.

Malfunction of the Immune System

In a healthy body, stress is supposed to come in waves — the system responds, resolves, and resets. But the immune system of someone with an autoimmune disease, the waves never stop. They stack.

First wave — stress

Stress, poor sleep, emotional pressure. The brain signals the adrenal system: “Stay alert, stay on guard.” Cortisol and adrenaline spike — helpful for the moment, costly if constant. The gut, highly tuned to stress signals, tightens its blood flow and loosens its barriers.

Second wave — gut permeability

When the tight junctions of the gut barrier become permeable, or when microbial balance breaks down, bacterial fragments, toxins, and undigested proteins slip through into the bloodstream, triggering alarm receptors (TLR4, NLRP3) and activating inflammatory pathways such as NF-κB. This chronic trickle of danger signals trains the immune system toward vigilance rather than tolerance.

Third wave — overload

More stress, another hit. Processed food, infection, antibiotics, environmental chemicals, disrupted sleep. The gut barrier weakens further. The bloodstream, once a quiet clean river, now carries debris the immune system was never meant to see all at once.

Role of dendritic cells

In this environment, dendritic cells are going about doing their job of collecting samples — bits of food proteins, bacterial signals, and also perfectly normal human tissue fragments shed in routine maintenance. But the context is chaos. Sirens are blaring. The air is filled with inflammatory smoke. They report back to immune headquarters carrying self-tissue evidence, but their message has changed: “This came from a disaster zone.”

Tolerance falters

Self-reactive immune cells hear the alarm as a call to arms. They activate and launch an attack — not out of malice, but out of misinformed duty. Which cells are activated and where defines which autoimmune disease results. The result isn’t random — it reflects which immune cells lose tolerance and which tissues become targeted. The specific immune players and the tissue environment shape the condition that emerges.

For example:

• Multiple sclerosis (MS) involves immune activity directed toward the central nervous system, where T cells, B cells, and myeloid cells contribute to inflammatory damage and demyelination in the brain and spinal cord.

• Neuromyelitis optica (NMO) is strongly associated with B cells producing antibodies (often against aquaporin-4), targeting the optic nerves and spinal cord.

• Systemic lupus erythematosus (lupus) involves a loss of tolerance to nuclear material, leading B-cells to produce multiple auto-antibodies that form immune complexes, which can deposit in tissues such as the skin, joints, kidneys, blood vessels, and brain.

• Endometriosis, although not a classic systemic autoimmunity, involves immune dysfunction and chronic inflammatory lesions. It involves an altered clearance of ectopic endometrial-like cells, allowing inflammatory lesions to persist outside the uterus and provoking immune activation.

• Crohn’s disease involves a loss of immune tolerance to gut microbes combined with barrier dysfunction, driving chronic inflammation where T cells, macrophages, and cytokines sustain immune activation in the gastrointestinal tract.

What differs between the different autoimmune diseases is not the immune system’s intention, but the context — which tissues are involved, what the triggers are, which are the disrupted tolerance checkpoints, and which communication signals fail to switch inflammation off.

Attempted resolution fails

After this loss of tolerance, the body tries to return to a tolerant state. Regulatory cells — Tregs and Bregs — try to calm things down, but there are too many fires, too many alerts, too many emergencies. Every time a firefighter puts out one blaze, another flares.

The nervous system's sympathetic branch drives the “fight-or-flight” response. It primes the immune system for immediate defence by releasing adrenaline and noradrenaline, which increase inflammatory cytokine output (IL-6, TNF-α) and mobilise immune cells into circulation. In autoimmunity, this alarm mode can stay switched on for months or years.

The hypothalamic–pituitary–adrenal (HPA) axis is the body’s central stress-response system. When it’s healthy, small daily pulses of the hormone cortisol help regulate inflammation — enough to control immune activity, not enough to suppress it. But during chronic stress or illness, this system becomes desensitised: either cortisol levels remain too high (so immune cells stop “listening”) or too low (so inflammation runs unchecked).

When the body is inflamed, the immune system sends alarm messages to the brain via cytokines and the vagus nerve. The brain can then amplify that signal, increasing fatigue, pain, anxiety, and immune activation in a feedback loop.

And so it goes:

• Inflammation disrupts hormones.

• Hormones disrupt the nervous system.

• The nervous system amplifies perceived threat.

• The gut barrier loosens further.

• More immune activation follows.

• The removal of waste compounds is impaired by inflammation and nutrient deficits, increasing inflammatory load and immune stimulation.

• Energy drops.

• Repair slows.

This is no longer an immune response. It is an immune system trapped in survival mode, responding rationally to an environment that never stops feeling dangerous.

No single moment caused autoimmunity. It was the accumulation, the lack of recovery, the inability to return to baseline. The misunderstanding isn’t cognitive — it’s contextual. The body doesn’t think it is attacking itself. It thinks it is still trying to survive.

Cycles of flare and partial recovery

This is why people with autoimmune diseases tend to go through cycles of flare and partial recovery. Flares happen when the total load exceeds the system's ability to regulate it. The load can stack from multiple directions, including stress, lack of sleep, gut permeability, infection, nutrient depletion, blood sugar dysregulation, overtraining, hormonal shifts, lack of recovery time. When enough of these overlap, the inflammatory milieu intensifies, dendritic cells become more “alarmist”, regulatory cells get outnumbered, and autoreactive cells attack → flare.

Partial recovery happens when the load drops enough for regulation to regain ground. This can come from sleep or rest, reduced stress, removing a trigger food or toxin, reduced demands, nervous system calming, better digestion, hormonal shifts. Now the milieu becomes less inflammatory, dendritic cells present information in a calmer way, Tregs and Bregs regain influence, cytokines drop, and symptoms ease → recovery window.

Collecting autoimmune diseases

Once self-reactivity begins, it can 'spread', which is why someone with one autoimmune disease has a higher risk of developing another. Tregs, Bregs, tolerogenic dendritic cells, and anti-inflammatory cytokines (like IL-10 and TGF-β) don’t act only on one tissue — they form a global regulatory network that keeps all self-reactivity under control. If that system is underpowered or chronically depleted, it doesn’t just fail in one place (e.g. the thyroid) — it fails everywhere. And when the immune system damages tissue, it releases new self-antigens — fragments of normal proteins that were previously hidden inside cells or behind barriers. Dendritic cells pick up those fragments and present them to the immune system, which can then begin targeting additional self-molecules. Over time, this process — called epitope spreading — can broaden the scope of autoimmunity from one target to many, or even from one organ to another.

Natural Mechanisms for Tolerance

Now that we understand at a basic level how the system is supposed to work and how it has gone wrong, we can look at the in-built mechanisms the body has to resolve autoimmunity.

Inflammatory milieu resolves

In order to restore tolerance, the immune milieu must switch from inflammatory to tolerant. This is essential for restoring balance because all of the cells in the immune system use the milieu as their signal to either attack or remain peaceful.

The milieu becomes tolerant when triggers for inflammation are removed. In the case of a virus entering the body, this will happen naturally once the virus has been neutralised. In the case of autoimmunity, the sources of pro-inflammatory cytokines are what needs to be removed to stop driving the overactive immune response. Sources of inflammatory cytokines include gut barrier permeability, lack of sleep, chronic stress, nutrient depletion, microbiome imbalance and toxic load. As pro-inflammatory cytokines are removed, the milieu resolves and then dendritic cells present information with calm signals, steering the system back towards tolerance.

Regulatory immune cells regain control

Regulatory T-cells (Tregs) and Regulatory B cells (Bregs) are the central architects of tolerance. They keep T-cells from overreacting by directly calming them through physical contact and by releasing chemical peace signals — particularly IL-10 (which quiets inflammation) and TGF-β (which promotes repair and tolerance). Tregs themselves need the right environment to become active. They are stimulated by IL-2 (a growth and survival signal for T cells), TGF-β (acting here as a teacher molecule), vitamin D and retinoic acid (the active form of vitamin A), and microbial metabolites such as butyrate (a short-chain fatty acid made by gut bacteria when they digest fibre). Together, Tregs and Bregs dampen inflammatory loops, retrain other immune cells, and re-establish the “don’t attack self” rule. Their expansion marks a decisive pivot from inflammation to tolerance.

In studies on mice, removing these regulatory cells precipitates autoimmune-like disease and replacing them ameliorates it. In humans with autoimmune diseases, Tregs and Bregs are not absent but undernourished and out-competed. They need to return to full function (increase in activity and number), in order to suppress autoreactive T-cells or B-cells and signal immune tolerance.

Once Tregs and Bregs have restored balance, autoreactive immune cells continue to circulate but they are functionally suppressed, no longer activated because the danger context has gone. Then over time, levels of autoreactive cells can decline because fewer new plasma cells are being activated, short-lived antibody-producing cells naturally die off, and long-lived plasma cells reduce output when antigenic stimulation drops.

Gut barrier repair

Gut barrier repair is an active biological process in which epithelial cells regenerate, reconnect, and reseal the microscopic gaps between them. Damaged or dying enterocytes are cleared and replaced by new cells migrating upward from the intestinal crypts. These cells re-establish tight junction proteins (occludin, claudins, zonula occludens) that restore selective permeability, while goblet cells thicken the protective mucus layer and Paneth cells secrete antimicrobial peptides to stabilise the local microbiome. As local inflammation subsides, cytokines like IL-10 and TGF-β promote tissue repair, fibroblasts remodel the underlying matrix, and the restored barrier once again limits antigen leakage and maintains immune tolerance.

In this new tolerant environment, dendritic cells in the GALT begin presenting antigens in a “peace-time” context, favouring Treg activation over attack. These newly educated regulatory cells then enter circulation, travelling to distant tissues (thyroid, joints, CNS) and extending tolerance system-wide. In this way, local repair in the gut translates into global immune recalibration.

The neuroimmune stress loop calms

To balance the immune system, balance needs to return to systems that directly tune immunity. When the stress load decreases and metabolic stability returns, sympathetic tone lowers. The body’s internal message shifts from “prepare for attack” to “repair and recover.” This reduction in sympathetic drive directly decreases inflammatory signalling throughout the body.

As recovery progresses, cortisol sensitivity returns. Immune cells begin responding again to cortisol’s regulatory signals, and the HPA axis re-establishes its natural diurnal rhythm — higher in the morning, lower at night — which stabilises the immune environment.

The vagus nerve, which runs from the brainstem to the heart, lungs, and gut, is the main channel of the parasympathetic nervous system — the “rest-and-digest” counterpart to fight-or-flight. When vagal tone is strong, the vagus nerve releases acetylcholine, a neurotransmitter that binds to receptors on immune cells (particularly macrophages) and inhibits the release of TNF-α and other pro-inflammatory cytokines. This is known as the cholinergic anti-inflammatory pathway.

Once nervous-system regulation returns, this amplification quiets. The brain begins interpreting immune activity as part of normal physiology again, rather than a continuing threat.

Lymphatic and glymphatic clearance improve

Inflammation resolution requires removal of immune debris. The lymphatic system clears inflammatory metabolites, antigens, and spent immune cells. The glymphatic system (brain lymphatic clearance) improves with sleep and reduced inflammation. This reduces ongoing immune stimulation.

Unlike the bloodstream, lymph has no pump; flow is generated by intrinsic vessel contractions, skeletal muscle, and breathing. A sluggish lymphatic system traps inflammation in tissues, while a healthy, moving one clears immune debris and sends a steady stream of “status updates” to the central immune network — enabling repair, balance, and long-term immune calm.

Metabolism shifts out of emergency mode

Resolution requires a metabolic shift. When the immune system detects threat, it switches to a high-speed, short-term energy mode called aerobic glycolysis. This means glucose is burned quickly, creating bursts of ATP and biosynthetic intermediates for cytokine production and cell replication. The by-products of this process reinforce inflammatory signalling. This metabolism is ideal for fighting infection or injury, but disastrous long-term.

Immune cells must shift from glycolysis to oxidative phosphorylation and fatty-acid oxidation. This slower energy pathway depends on healthy mitochondria, oxygen availability, and micronutrient cofactors such as magnesium, iron, B-vitamins, and coenzyme Q10.

When systemic metabolism stabilises — rhythmic cortisol, steady glucose, efficient mitochondria — immune regulation follows.

Supporting Natural Tolerance

Supporting immune resolution pathways

Certain inputs directly supply the building blocks and signals required to shift the immune environment towards resolution. Omega-3 fatty acids, particularly EPA and DHA from oily fish, are literal precursors for resolvins and protectins — molecules the body uses to end inflammation safely. Polyphenols (found in berries, olive oil, green tea, herbs, and cocoa) influence gene expression and cell signalling by dampening NF-κB, one of the body’s main inflammatory switches. Specific spices, such as curcumin and ginger don’t just reduce inflammation in a general sense, they actively modulate cytokine production and intracellular signalling, lowering IL-6 and TNF-α while nudging immune cells toward a regulatory, non-reactive state.

The body also requires sufficient antioxidant micronutrients — vitamin C, vitamin E, selenium and zinc — because chronic inflammation is tightly linked to oxidative stress. Without enough antioxidant capacity, inflammatory reactions perpetuate themselves in a loop: immune cells generate free radicals, tissues become stressed, and more inflammatory signals are triggered. Antioxidant nutrients break that cycle, protecting cells and allowing pro-resolving pathways to take over.

Just as important as what the body needs is what it needs less of. Glucose spikes, alcohol, cigarettes, trans fats, ultra-processed foods and oxidised, omega-6–rich industrial oils can raise oxidative/inflammatory tone, amplify inflammatory signalling and make the immune environment more reactive by promoting oxidative stress, stimulating NF-κB, and disrupting stable blood sugar and membrane integrity. Reducing these inputs lowers the baseline inflammatory tone, making it possible for the immune system to shift out of “danger mode” and into a state where resolution, repair, and immune balance are supported.

Supporting Tregs and Bregs

Tregs and Bregs are metabolically intensive cells (this means that they are hungry!) but not in the same way as inflammatory immune cells. Pro-inflammatory T and B cells run primarily on rapid glycolysis, burning glucose to expand quickly and mount an aggressive response. Regulatory cells, in contrast, rely on mitochondrial, oxidative metabolism — drawing energy from fatty acids, ketones, and metabolites like butyrate. Their function depends less on fast fuel and more on efficient mitochondria, steady energy flow, antioxidant protection, and a dense supply of enzymatic cofactors. In short, they are not sugar-hungry like inflammatory cells — they are mitochondria-hungry and micronutrient-hungry. This is why a healthy gut and nutrient-dense diet are vital.

Butyrate is one of the most powerful drivers of immune regulation and it originates in the gut. Microbes in the large intestine produce butyrate when they ferment specific types of soluble and prebiotic fibres. Butyrate doesn’t just reduce inflammation; it actively signals immune cells to shift into regulatory phenotypes, increasing Treg and Breg activity and helping rebalance inappropriate immune responses. Butyrate-supporting foods include alliums, prebiotic-rich vegetables like artichoke, leafy greens, herbs, sea vegetables, non-starchy vegetables, ferments, foraged greens, medicinal mushrooms like reishi, chaga, lion’s mane, turkey tail, and polyphenol-rich plants such as oregano, thyme, rosemary, turmeric, ginger, cloves, cinnamon and berries.

Herbs and medicinal mushrooms further support immune calibration through additional pathways.
For example Reishi helps promote Treg expansion and reduces over-active inflammatory signalling. Lion’s mane reduces inflammatory stress upstream, partly by modulating NF-κB signalling and enhancing Nrf2-driven cellular resilience. Oregano, thyme, rosemary and garlic influence microbial balance, helping discourage inflammatory overgrowth while supporting a diversified microbiome environment.

To maintain their regulatory identity and suppress inflammation, Tregs and Bregs require a convergence of signals and resources. Vitamins and minerals act as non-negotiable cofactors for the metabolic pathways that keep them functional. Vitamin D directly drives Treg differentiation and restrains inflammatory T-cell activity. Vitamin A (as retinoic acid) is crucial for immune tolerance in the gut, where the largest population of regulatory cells is trained. Magnesium is required for ATP (energy) generation, immune signalling, and for activating vitamin D. Zinc stabilises regulatory T-cell function and limits excessive inflammatory cytokine activity. Selenium protects mitochondria from oxidative stress via glutathione peroxidase, helping regulatory cells stay functional in high-inflammation environments. B-vitamins power the mitochondrial energy cycle and methylation pathways that preserve regulatory cell identity. Iron, when balanced, supports mitochondrial enzymes, but in excess drives inflammation. Omega-3 fatty acids give rise to anti-inflammatory lipid mediators that tilt signalling toward resolution rather than attack.

Ketone bodies, when present, act as signalling molecules that suppress NLRP3 inflammasome activity and promote Treg differentiation. Ketone bodies rise with sustained carbohydrate restriction or fasting (often within 24–72 hours).

All of these inputs converge on a central reality: regulatory immune cells don’t just need the inflammatory fire turned down — they need to be built, fuelled, protected, and biochemically instructed to do their job. Their survival and stability depend on mitochondrial output, which in turn depends on a constant supply of micronutrient cofactors. When any part of this chain is weak, regulatory cells lose stability and immune behaviour shifts back toward inflammatory dominance.

This matters particularly in early autoimmune recovery, where anti-inflammatory diets such as AIP or ketogenic approaches naturally reduce glucose-driven inflammatory immune activation and provide fats and ketones that regulatory cells can readily use. However, without sufficient micronutrients, polyphenols, minerals, essential fats and gut-derived signalling molecules, the conditions for inflammation may change, but the capacity for regulation doesn’t fully develop. Recovery is therefore not just about reducing immune activation — it is equally about supplying the metabolic and nutritional resources that allow regulatory cells to exist, persist, and lead the immune system back toward balance. If supporting recovery is the goal, then consuming what would for a healthy person be a balanced, nutritious diet is not sufficient. The body needs extra nutrients during recovery and supplementation is a useful tool in this regard.

Vitamin D isn't really a vitamin, but more like a hormone for the immune system (technically a precursor to the hormone calcitriol). It steers immune cells toward tolerance rather than attack. In the case of autoimmunity, there are many factors at play here. Gut dysbiosis reduces vitamin D absorption, inflammation burns through a lot of vitamin D, and sluggish liver, kidneys and immune system do a poor job of converting what little there is to its active form, meaning that diet and sun exposure are generally insufficient, and testing with targeted supplementation is commonly required. Vitamin A — from liver, egg yolks, and colourful carotenoid-rich plants — works alongside vitamin D to regulate mucosal immunity, particularly in the gut, where much of immune education takes place.

Finally, the immune system needs contact with the wider biological world in order to learn appropriate tolerance. Time outdoors, inhaling fresh air, touching soil, forest exposure, and spending time in diverse natural environments all introduce low-grade, non-threatening microbial inputs that help train the immune system toward regulation rather than reactivity. Combined, these inputs signal safety, nourish regulatory pathways, and gradually rebuild the body’s ability to control inflammation instead of amplifying it.

Supporting barrier repair (gut, brain, lungs, skin)

To reduce aberrant immune activation from particles entering through a permeable gut wall, foods and other inputs that trigger inflammation need to be removed. Tolerance can be individual, but there are some key foods that are likely culprits for anyone with autoimmune disease. For example gluten, casein, lectins, and certain seed oils can increase intestinal permeability or bind to immune receptors like TLR4, mimicking bacterial signals. Refined sugars and processed fats generate oxidative stress and NF-κB activation, the molecular switch that amplifies inflammation. Modern food additives and emulsifiers disturb the gut microbiome and damage mucus layers. By removing these foods, the triggering of false alarms reduces and gives the immune system fewer reasons to fire.

Removing alcohol and NSAIDs (like ibuprofen, naproxen and asprin) also reduces immune activation. This is because alcohol and its metabolite acetaldehyde disrupt tight junctions by changing the cell membrane’s fluidity and interfering with the proteins that hold neighbouring cells together. NSAIDs block prostaglandin synthesis, which is essential for mucus production and blood flow that protect the gut lining. When they’re suppressed, the mucosa thins and becomes vulnerable to acid and bile injury.

As well as removing damaging inputs, the system needs to have adequate nourishment in order to repair, including amino acids and structural nutrients. Adequate dietary protein provides the raw materials for cell repair, while specific nutrients like glutamine, zinc, vitamin A, and omega-3 fatty acids directly support tight junction function — the microscopic seals between cells that prevent unwanted leakage. Omega-3s help reduce inflammatory disruption around barrier tissues, and collagen-rich foods (bone broth, connective tissue, skin, gelatin) provide glycine and other building blocks that support tissue strength and repair. Plant compounds also play an active protective role. Polyphenols in foods like berries, cocoa and pomegranate signal to barrier cells to tighten their junctions and resist inflammation-driven breakdown.

Supporting other inter-woven systems

Restoring function to the nervous system, endocrine system and lymphatic system is part of resolving the immune system. As the HPA axis regains rhythm, sympathetic overdrive eases, and vagal tone increases, the entire neuroimmune dialogue changes tone. Cytokine levels fall, Tregs and Bregs regain support, and tissues receive fewer “danger” broadcasts from the brain. This is why restoring sleep, safety, rhythm, and calm isn’t just psychological — it’s biochemical. The nervous system, endocrine system, and immune system together re-establish a state of perceived safety, and tolerance follows. Increasing vagal tone through slow breathing, relaxation, laughter, singing, or even social safety cues literally tells the immune system: “You are safe; stand down.”

The lymphatic system clears immune debris, excess cytokines and inflammatory by-products from tissues. Gentle movement, diaphragmatic breathing, hydration, and a responsive circadian rhythm all enhance lymphatic circulation.

Summary

The immune system is supposed to launch targeted attacks when necessary, then return to baseline calm. Autoimmune disease results from imbalances in the system that result in auto-reactive cells being activated. The body has built-in mechanisms to return to homeostasis, which are directly impacted by the environmental inputs into the body. Biological systems calibrate through repetition. The immune, metabolic, endocrine and nervous systems tune their responses based on steady patterns and dependable signals rather than isolated interventions.