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Immune system and infections

Most of the immune system sits at the gut wall. That is where it is settled what gets taken up and what gets fended off — and that decision rests on a mucus layer, a cell layer with tight junctions and the antibody sIgA.

So here we measure not just nutrients in blood, but the barrier itself: sIgA, zonulin, calprotectin — and the cofactors without which the defence does not work.

Figure 1 · The gut barrier in cross-section

Four layers decide between tolerance and defence

A few micrometres separate the gut contents from the blood: mucus, sIgA, a cell layer with tight junctions and, behind it, the gut-associated immune system. This arrangement steers the balance between tolerance and immune response to foreign substances.

State A Barrier intact
·Gut contents with food and microbes·Mucus layer dense, sIgA in the normal range·Cell junctions closed·Immune cells quiet
—The mucus layer keeps most microbes at a distance from the cell surface.
—sIgA binds germs while still in the lumen and at the same time helps shape the composition of the gut flora.
—Uptake happens through the cell, along the route intended for it.
—The immune cells behind stay uninvolved — that is the normal case, not the exception.
Tolerance is active work: the gut lets foreign substances pass every day without reacting to them.
State B Barrier irritated
·Gut contents with irritants·Mucus layer thinner, sIgA lower·Cell junctions partly loosened·Immune cells activated
—Zonulin opens the cell junctions — so far it is the only described endogenous regulator of these junctions.
—Components from the lumen reach the blood side without taking the intended route through the cell.
—The immune cells behind are activated; inflammatory signals rise.
—Histamine adds to the irritation and is broken down less well when the mucosa is irritated.
A disturbed barrier can activate immune cells and thereby raise the risk of persistent inflammation in various tissues. It is not a diagnosis in its own right.
Measurable values
sIgA in stool The antibody of the mucosa. It binds germs in the lumen and at the same time helps shape the composition of the gut flora.Leaky Gut & Resorption · Microbiome
Zonulin Governs the opening of the cell junctions. Raised values are taken as a sign of a more permeable barrier.Gut microbiome analysis · Leaky Gut & Resorption
Calprotectin Shows whether neutrophil defence cells have migrated into the gut wall — a marker of inflammation, not of permeability.Gut microbiome analysis
Alpha-1-antitrypsin Rises when protein is lost through the gut wall. Adds to the picture drawn by zonulin and calprotectin.Leaky Gut & Resorption

Zonulin counts as a marker of barrier function, but the literature also discusses it critically — the assays partly pick up related proteins. We therefore report the value alongside the other markers, not on its own.

10¹⁴ Microbes per gram of gut contents According to review articles, up to a hundred trillion microorganisms live per gram of large-intestine contents, spread across about 500 to 1,000 species. The mucosa is in constant contact with them.Review on sIgA, PMC 2020
one cell layer That is how thin the separation is The gut barrier consists of a single layer of epithelial cells, joined by tight junctions into a physical barrier.Review on barrier function, PMC 2023
47 kDa Zonulin, the only known regulator Zonulin is so far the only described endogenous modulator of the cell junctions and is thereby involved in the balance of tolerance and immune response.Fasano A, Physiological Reviews 2011
Figure 2 · Stress and immune response

How strain turns into weakened defence

Short stress mobilises the defence. Sustained stress shifts it: the cells respond less sensitively to cortisol, inflammatory signals stay high, sIgA at the mucosa falls. That is the route described in the literature by which strain turns into more frequent infections.

Step 01 Strain A stimulus is judged as strain — physical or psychological, acute or sustained.
Daily cortisol profile
Step 02 Cortisol rises Useful in the short term: cortisol dampens excessive inflammation and mobilises defence cells.
CortisolDHEA
Step 03 The brake bites less well Under sustained strain the immune cells respond less sensitively to cortisol. The damping effect drops off and inflammatory signals stay high.
hs-CRP
Step 04 Defence at the mucosa falls sIgA at the mucosa drops and the barrier becomes more permeable. In studies, upper-respiratory infections became more frequent.
sIgA in stoolZonulin
Irritation comes from two sides
Inside Histamine and mediators Histamine is released from mast cells on irritation, but it also comes from food and is produced by some gut bacteria. It is broken down at the gut wall by the enzyme diamine oxidase.
From mast cellsFrom foodFrom gut bacteriaBroken down by DAO
Outside What strains the barrier The influences named again and again in review articles when the mucosa and gut flora fall out of balance. None of them acts alone — it is the sum over time.
MedicinesAlcoholOne-sided dietInfectionsSustained stressLittle fibre
up first, then down Short and long stress pull in opposite directions Acute strain mobilises the defence. In meta-analyses, chronic strain is associated with dampened immune function and raised inflammatory markers.Segerstrom & Miller, Psychological Bulletin 2004, over 300 studies
less sensitive Glucocorticoid resistance Under sustained stress, immune cells respond more weakly to cortisol. The damping effect on inflammation drops off, even though the cortisol value itself need not be low.Cohen S et al., PNAS 2012
sIgA falls Defence at the mucosa In studies of students and athletes, sustained strain was associated with lower sIgA values and more frequent upper-respiratory infections.Reviews on sIgA and strain
Tolerance or defence The barrier has a say Together with the gut-associated immune tissue, the barrier steers the balance between tolerance and immune response to foreign substances.Fasano A, Physiological Reviews 2011
Cofaktoren

What defence depends on

For every nutrient here there is a claim authorised by the European Commission on the normal function of the immune system. That is not a statement that a supplement prevents infections. For each one we also state whether and how we can measure it.

Authorised claim Vitamin D Formed in the skin in sunlight; in Germany very little is formed in winter. Immune cells carry receptors for it. Contributes to the normal function of the immune system.Measurable: Vitamincheck Basis · OM Vital
Authorised claim Zinc A cofactor in hundreds of enzymes, including the division of immune cells. A deficiency shows quickly. Contributes to the normal function of the immune system.Measurable: Vollblutmineralanalyse · OM Vital
Authorised claim Selenium Part of the protective enzymes that shield cells from oxidative load during an immune response. Contributes to the normal function of the immune system.Measurable: Vollblutmineralanalyse · OM Vital
Authorised claim Iron Needed for cell division and oxygen transport. During an infection the iron value drops temporarily — that is a response, not a deficiency. Contributes to the normal function of the immune system.Measurable: Vollblutmineralanalyse · OM Vital (ferritin)
Authorised claim Vitamin C Water-soluble, not stored, and concentrated at high levels inside immune cells. Contributes to the normal function of the immune system.Not a self-test — a medical practice can measure it, ask our expert network about it
Authorised claim Vitamin A Involved in the renewal of skin and mucous membranes — the surface that makes first contact. Contributes to the maintenance of normal mucous membranes and to the normal function of the immune system.Not a self-test — a medical practice can measure it, ask our expert network about it

Whether a supplement suits you, and at what amount, you discuss with a practitioner once the lab report is in. Zinc and selenium are not harmless at high doses — the upper limits are lower than many people assume.

Quellen
  1. Fasano A, Zonulin and Its Regulation of Intestinal Barrier Function, Physiological Reviews 2011.
  2. Secretory IgA in Intestinal Mucosal Secretions as an Adaptive Barrier against Microbial Cells, PMC 2020.
  3. Secretory IgA's Complex Roles in Immunity and Mucosal Homeostasis in the Gut, PMC 2013.
  4. Evaluating Prophylactic Effect of Bovine Colostrum on Intestinal Barrier Function, PMC 2023 — review of the barrier as a single cell layer.
  5. Segerstrom SC, Miller GE, Psychological stress and the human immune system: a meta-analytic study of 30 years of inquiry, Psychological Bulletin 2004.
  6. Cohen S et al., Chronic stress, glucocorticoid receptor resistance, inflammation, and disease risk, PNAS 2012.
  7. Regulation (EU) No 432/2012 with the list of authorised health claims.
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Why look at the gut for immune questions?

Because most of the immune tissue sits there, and that is where the choice between tolerance and defence is made. The barrier is a single layer of cells with mucus in front and immune cells behind.

So the measurement covers not just whether nutrients are present but whether the mucosa can do its job: sIgA, zonulin and calprotectin from stool.

Is “leaky gut” a diagnosis?

No. Increased permeability of the gut barrier can be measured and is well described in research, but it is not a disease in its own right.

Zonulin as a marker is debated in the specialist literature too, because some assays also pick up related proteins. We therefore report the value alongside the other markers, not as a finding on its own.

What has histamine to do with the immune system?

Histamine is a messenger substance released from mast cells when they are irritated. It also comes from food and is produced by some gut bacteria.

It is broken down at the gut wall by the enzyme diamine oxidase. We measure both sides together: histamine in stool and DAO activity in blood — the substance and the enzyme that clears it. That is exactly what sets this apart from a DAO measurement on its own, which the guidelines rightly do not accept as sole proof of histamine intolerance. Read as a pair and set against your symptoms, the two values show where the problem lies — they do not make a diagnosis.

Does stress weaken defences?

Brief stress mobilises it, sustained stress shifts it. In a meta-analysis of more than 300 studies, chronic strain was associated with dampened immune function.

The mechanism described: immune cells respond less sensitively to cortisol, inflammatory signals stay up, and sIgA at the mucosa falls. That is why the daily cortisol profile belongs here.

Can I strengthen my immune system?

This page makes no claim about that. What is authorised are claims about normal function: vitamin D, zinc, selenium, vitamin C, vitamin A and iron contribute to the normal function of the immune system.

What is short in your case, and whether a supplement makes sense, comes from the lab report and from talking to a practitioner. Markers we do not offer as a self-test can be measured at a medical practice — ask our expert network about them. Fever, persistent infections or blood in the stool belong in a medical practice for assessment.

Your Partner in Health

All figures here come from studies and describe groups, not individual cases. Fever, persistent infections or blood in the stool belong in a medical practice for assessment.