Pollenassoziierte Nahrungsmittelallergie (Kreuzallergie): the pathway in the body

Pollenassoziierte Nahrungsmittelallergie (Kreuzallergie) is part of the pathway “IgE antibodies and mast cells”. This page shows the whole pathway; the station of Pollenassoziierte Nahrungsmittelallergie (Kreuzallergie) is highlighted.

Where this laboratory value sits: Similar protein — PR-10, profilins in plants. Plants make proteins that are very similar across species. IgE against the birch pollen protein Bet v 1 also recognises related PR-10 proteins, for example in apple, hazelnut or carrot. This is called cross-reaction. Source 4

In brief

IgE is the antibody class that the immune system forms against certain proteins from pollen or food and that binds tightly to mast cells. When the protein meets this IgE again, the cells release histamine and leukotrienes within minutes.

The pathway step by step

Each station states what the compound does there. Three signs: ↑ supplies — builds up or makes available · ↓ depletes — inhibits, consumes or withholds · ↕ both, depending on amount. Behind it stands what the statement rests on: established physiology, observed in studies, or contested. The signs do not grade; they name the direction.

1. Foreign protein → Antigen presentation Dendritic cells absorb the protein, cut it up and carry fragments to the nearest lymph node. There they display them to T helper cells on their surface. Source 1, 14↑ supplies Together with the fragment, dendritic cells pass on signals that decide which type of helper cell develops. Messengers from irritated skin or mucosa steer the response towards the Th2 type. observed in studies Source 11, 14
   ⚖ When the balance tips

   too much — If the tissues release many alarm signals such as IL-33 or TSLP, dendritic cells steer more T helper cells towards Th2.

   too little — Without these signals, the same contact tends to produce regulatory T cells that dampen the response.

   observed in studies · Source 11, 14

2. Antigen presentation → Th2 and Tfh cells Type 2 T helper cells and follicular helper cells recognise the fragment and release interleukin-4 and -13. Together with contact via CD40, this gives the B cell the signal to switch to IgE. Source 3, 14↑ supplies IL-4 or IL-13 together with the CD40 signal are the precondition for a B cell to switch to IgE. If either signal is missing, no IgE is formed. established physiology Source 3
   ⚖ When the balance tips

   too much — If many helper cells release IL-4, more B cells switch to IgE, and the amount of IgE in the blood rises.

   too little — If other signals such as interferon-γ or IL-10 predominate, B cells tend to switch to other classes, for example IgG4.

   established physiology · Source 3, 1

3. Th2 and Tfh cells → Class switch to IgE AID Inside the B cell, the enzyme AID cuts the DNA in the antibody genes. The section for the antibody's stem is exchanged for the one for IgE; the arms that bind the antigen stay the same. Source 3↑ supplies After the switch the cell makes IgE with the same binding site as before. The new stem determines that this antibody binds to mast cells and basophils. established physiology Source 3, 1
   ⚖ When the balance tips

   too much — If many B cells switch to IgE and some of them mature into long-lived plasma cells, IgE production persists for a long time.

   too little — If no switch to IgE occurs, the B cells go on making other antibody classes, and no IgE forms against this protein.

   observed in studies · Source 3, 1

4. Class switch to IgE → IgE in the blood Plasma cells release IgE into the blood. It stays free in the blood for only a few days; most of it sits on cells. What is measured is this free IgE against particular proteins. Source 1↑ supplies Free IgE is the pool from which the binding sites on mast cells and basophils are filled. The more free IgE, the more FcεRI these cells make and the more of it is occupied. established physiology Source 1, 2
   ⚖ When the balance tips

   too much — If there is much IgE against a protein in the blood, more mast cells are loaded with it. Detection in the laboratory shows contact by the immune system, not whether the body reacts on eating.

   too little — If hardly any IgE against a protein is detectable, mast cells carry hardly any antibody against it; processes without IgE are not captured by this measurement.

   established physiology · Source 1, 11

5. IgE in the blood → IgE on mast cells IgE binds very tightly to the FcεRI receptor on mast cells in skin and mucosa and on basophils in the blood. It stays there for weeks. This loaded state is called sensitisation. Source 1, 2↑ supplies The bound IgE primes the mast cell: it now responds specifically to the protein its IgE is directed against. Without renewed contact it stays at rest. established physiology Source 2
   ⚖ When the balance tips

   too much — If many receptors are occupied by IgE against the same protein, even a small amount of it is enough to link many receptors.

   too little — If only a few receptors carry matching IgE, two neighbouring ones are rarely hit at once, and the cell tends to stay at rest.

   established physiology · Source 2, 1

6. Protein meets IgE → Cross-linking of IgE If the protein binds two neighbouring IgE molecules, their receptors move together. This activates enzymes on the inner side of the membrane, and calcium rises inside the cell. Source 2, 10↑ supplies Cross-linking is the actual start signal. Only when two receptors are linked does the cell pass the signal inside; a single bound IgE is not enough. established physiology Source 2
   ⚖ When the balance tips

   too much — If many receptors are cross-linked at once, more calcium flows in, and more storage granules are emptied at the same time.

   too little — If only a few receptors are cross-linked, the rise in calcium stays small, and the cell releases little or nothing.

   established physiology · Source 10, 2

7. Cross-linking of IgE → Mast cell empties · Calcium The rise in calcium makes the storage granules fuse with the cell membrane and release their contents to the outside. This happens within minutes. Source 2, 10↑ supplies Degranulation releases large amounts of ready-stored messengers in a short time. At the same time the cell starts to make further messengers anew. established physiology Source 2
   ⚖ When the balance tips

   too much — If many mast cells empty at once, the messengers reach the blood in large amounts, beyond the site of contact.

   too little — If only a few cells empty, the action of the messengers stays confined to the immediate surroundings.

   established physiology · Source 2

8. Mast cell empties → Histamine, tryptase The granules contain ready-made histamine, enzymes such as tryptase and other substances. The mast cell makes histamine beforehand from the amino acid histidine; for this it needs vitamin B6. Source 2, 9↕ both, depending on amount Histamine widens blood vessels, makes them leakier and stimulates nerve endings and smooth muscle. How strongly depends on amount, site and receptor. established physiology Source 2, 9
   ⚖ When the balance tips

   too much — If more histamine is released than the degrading enzymes can handle, it binds more receptors at once: vessels widen, skin and mucosa swell.

   too little — If little histamine is released, its action stays local and fades quickly once it is broken down.

   established physiology · Source 2, 9

9. Mast cell empties → Leukotrienes 5-Lipoxygenase · Glutathione The activated cell makes leukotrienes anew from the arachidonic acid of its membrane. LTC4 synthase attaches glutathione; this yields the sulfidoleukotrienes measured by the CAST method. Source 6, 13, 8↕ both, depending on amount Sulfidoleukotrienes contract smooth muscle, for example in the bronchi, and make small vessels leakier. They act longer than histamine and attract further immune cells. established physiology Source 6
   ⚖ When the balance tips

   too much — If more arachidonic acid flows into the 5-lipoxygenase pathway, for example when cyclooxygenase is inhibited, more leukotrienes form, and their action on muscle and vessels lasts longer.

   too little — If 5-lipoxygenase is inhibited, fewer leukotrienes form; histamine from the granules is unaffected.

   observed in studies · Source 6, 12

10. Histamine, tryptase → Action in the tissue The messengers act on nearby vessels, smooth muscle, nerve endings and glands. Depending on the site, this involves mouth and throat, skin, gut or airways. Source 2, 11↕ both, depending on amount At the site of contact the messengers widen vessels and make them leakier, trigger itching via nerve endings and contract smooth muscle. Where this happens depends on the route of the protein. established physiology Source 2, 11
    ⚖ When the balance tips

    too much — If the messengers reach the circulation in large amounts, they act on many organs at once; if many vessels widen at the same time, blood pressure falls.

    too little — If the release stays small, the action is confined to the site of contact, for example the lining of the mouth.

    established physiology · Source 2, 11

Further stations

• Foreign protein — from pollen or food The immune system can recognise certain proteins from pollen, foods or animal hair as antigens. Some people form IgE antibodies against some of them; most people tolerate the same proteins. Source 1, 11↑ supplies The protein supplies the sections the response is directed against. Whether this leads to tolerance or to an IgE response depends on where contact happens, on the amount and on the signals in the surroundings. established physiology Source 1, 11
  ⚖ When the balance tips

  too much — If a protein repeatedly meets an inflamed skin or mucosal barrier, studies show Th2 signals and IgE arise more readily; contact via the gut more often leads to tolerance.

  too little — If a protein never comes into contact with the immune system, neither tolerance nor IgE against it develops.

  observed in studies · Source 11

• Protein meets IgE — renewed contact If the protein enters the body again, for example via mouth, gut or airways, it meets mast cells whose IgE recognises it. A protein with several matching sites binds several IgE molecules at once. Source 2↑ supplies Only renewed contact triggers the reaction. Whether it happens depends on how much protein reaches the mast cells unchanged. established physiology Source 2, 11
  ⚖ When the balance tips

  too much — If much unchanged protein reaches the mast cells, more cells respond at once, and the reaction extends beyond the site of contact.

  too little — If heat or digestion breaks the protein down before it reaches the mast cells, the binding sites stay free.

  established physiology · Source 2, 4

• Similar protein — PR-10, profilins in plants Plants make proteins that are very similar across species. IgE against the birch pollen protein Bet v 1 also recognises related PR-10 proteins, for example in apple, hazelnut or carrot. This is called cross-reaction. Source 4↑ supplies A similar protein from food can cross-link the same IgE as the pollen it was formed against. Contact via the airways is thus enough for a reaction on eating. established physiology Source 4
  ⚖ When the balance tips

  too much — If there is much IgE against a pollen protein, it often recognises several related food proteins. As PR-10 proteins and profilins break down quickly under heat and stomach acid, the reaction mostly affects only the mouth.

  too little — If the food protein is cooked or little matching IgE is present, it finds hardly any binding sites, and the mast cells stay at rest.

  established physiology · Source 4

• Activation without IgE — additives, salicylate Some substances activate mast cells and basophils without IgE, for example via the receptor MRGPRX2. Salicylates inhibit cyclooxygenase; arachidonic acid then flows increasingly into leukotriene formation. Source 5, 12↕ both, depending on amount The route without IgE leads to the same result: the cell releases histamine or forms leukotrienes. Which additives trigger this in humans, and in what amount, is documented only for individual substances. contested Source 5, 7
  ⚖ When the balance tips

  too much — If such a substance arrives in larger amounts, it activates more cells; the reaction then follows the amount and does not require prior sensitisation.

  too little — If the amount stays small, the cells mostly do not respond. An IgE test does not capture this route; in the laboratory it is examined via the release of leukotrienes from blood cells.

  contested · Source 7, 8

  Field of research — Reactions to colourings and preservatives are studied mainly in recurrent skin reactions with wheals. Source 7

Cofactors in this pathway

• Histidine — Starting material from which the mast cell makes its histamine via histidine decarboxylase Source 9In the ORY catalogue as a laboratory value: Histidin
• Vitamin B6 — As pyridoxal phosphate, cofactor of histidine decarboxylase, which makes histamine for the storage granules Source 9In the ORY catalogue as a laboratory value: Vitamin B6
• Calcium — Its influx after cross-linking triggers the emptying of the storage granules Source 10, 2In the ORY catalogue as a laboratory value: Calcium (intrazellulär)
• Arachidonic acid — Membrane fatty acid from which 5-lipoxygenase forms the leukotrienes Source 6In the ORY catalogue as a laboratory value: Arachidonsäure (AA)
• Glutathione — Attached to LTA4 by LTC4 synthase; this yields the sulfidoleukotrienes Source 13In the ORY catalogue as a laboratory value: Glutathion (GSH)

What acts on this pathway

• H1 antihistamines — Medicines in this group occupy the H1 receptor and hold it in its inactive form. Histamine can then no longer bind there; leukotrienes and tryptase act independently of this. Source 15

Sources

1. Gould HJ, Sutton BJ. IgE in allergy and asthma today. Nat Rev Immunol 2008 · PubMed 18301424
2. Galli SJ, Tsai M. IgE and mast cells in allergic disease. Nat Med 2012 · PubMed 22561833
3. Tong P, Wesemann DR. Molecular Mechanisms of IgE Class Switch Recombination. Curr Top Microbiol Immunol 2015 · PubMed 25553793
4. Poncet P, Sénéchal H, Charpin D. Update on pollen-food allergy syndrome. Expert Rev Clin Immunol 2020 · PubMed 32691654
5. McNeil BD, Pundir P, Meeker S et al. Identification of a mast-cell-specific receptor crucial for pseudo-allergic drug reactions. Nature 2015 · PubMed 25517090
6. Peters-Golden M, Henderson WR Jr. Leukotrienes. N Engl J Med 2007 · PubMed 17978293
7. Reese I, Zuberbier T, Bunselmeyer B et al. Diagnostic approach for suspected pseudoallergic reaction to food ingredients. J Dtsch Dermatol Ges 2009 · PubMed 19054425
8. de Weck AL, Sanz ML. Cellular allergen stimulation test (CAST) 2003, a review. J Investig Allergol Clin Immunol 2004 · PubMed 15736710
9. Moriguchi T, Takai J. Histamine and histidine decarboxylase: Immunomodulatory functions and regulatory mechanisms. Genes Cells 2020 · PubMed 32394600
10. Ma HT, Beaven MA. Regulators of Ca(2+) signaling in mast cells: potential targets for treatment of mast cell-related diseases? Adv Exp Med Biol 2011 · PubMed 21713652
11. Sicherer SH, Sampson HA. Food allergy: A review and update on epidemiology, pathogenesis, diagnosis, prevention, and management. J Allergy Clin Immunol 2018 · PubMed 29157945
12. Picado C. Mechanisms of aspirin sensitivity. Curr Allergy Asthma Rep 2006 · PubMed 16579869
13. Lam BK. Leukotriene C(4) synthase. Prostaglandins Leukot Essent Fatty Acids 2003 · PubMed 12895593
14. Kubo M. T follicular helper and T(H)2 cells in allergic responses. Allergol Int 2017 · PubMed 28499720
15. Simons FE, Simons KJ. Histamine and H1-antihistamines: celebrating a century of progress. J Allergy Clin Immunol 2011 · PubMed 22035879

Whole pathway: IgE antibodies and mast cells

Related pathways

• Borrelia — antigen presentation
• IgG antibodies to food — antigen presentation
• Histamine — Histidin, Vitamin B6
• Liver enzymes — Vitamin B6, Glutathion (GSH)
• Nitrosative stress — Calcium (intrazellulär), Glutathion (GSH)

As of 2026-10-05. Draft written by Claude to schema v2; sources checked in PubMed; expert approval pending
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