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Mast cells - immune system and allergies

What are mast cells? Mast cells are cells belonging to the body that are, among other things, responsible for immune defense. They support the body in fending off pathogens such as viruses, bacteria, fungi, or parasites, but also have an important function in allergic reactions. Histamine, as a mast cell mediator, also plays a pivotal role in immunology and allergies.

The connection between mast cells, allergies, and the immune response

Allergic diseases exist in numerous forms: allergic asthma, atopic dermatitis, hay fever, hives (urticaria), food allergies, or allergic alveolitis (inflammation of the alveoli). IgE-mediated allergies are classified as type I allergies. These affect an estimated 20% of the total global population. Many individuals have a genetic predisposition to react to harmless environmental antigens.

In addition, there are environmental influences such as air pollutants, viral infections, allergens, and other sensitizers. It has been proven that people who grew up on a farm or were looked after in a daycare center during early childhood are less affected by allergies. This is most likely due to the early contact of the immune system with specific pathogens, which can prevent the tendency toward increased allergic reactions.

How do mast cells trigger an allergic reaction?

Mast cells can not only exacerbate allergy-related symptoms but also trigger an allergy. Inside the mast cells are various messenger substances, including histamine. Histamine influences the effect of mast cells in allergic reactions. Certain factors such as stress, infections, medications, alcohol, sudden changes in temperature, insect stings, or food can be triggers that cause mast cells to release these messenger substances, including histamine.

Mast cells in the skin ultimately cause spotting, wheals, swelling, itching, or blisters. Mast cells in internal organs such as the gastrointestinal tract or the liver can lead to abdominal pain, nausea, diarrhea, or fatigue. A high number of or altered mast cells can be an indication of a mast cell disorder, such as mastocytosis or mast cell activation syndrome (MCAS). You can find out how to recognize these in this article.

How do mast cells contribute to the body's own defense?

Mast cells are localized in well-perfused skin tissue, in the gastrointestinal tract, and in the airways, which ensures close contact with the environment. Acute allergic reactions can occur within just a few seconds or minutes. Allergens bind via IgE molecules to the Fc receptor FcεRI on basophils and mast cells. The receptors cross-link after antigen contact, which makes the cells extremely active.

As a result, mast cells release substances stored in so-called secretory granules (cells specialized for secretion), such as histamine, cytokines, proteoglycans (e.g., heparin), growth factors, and enzymes (e.g., tryptase). This happens through a process called degranulation, during which the vesicles within a cell fuse with the cell membrane and release secretions. This is actually a normal process controlled by the immune system to combat pathogens. A disturbance in degranulation can also disrupt the immune defense.

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How are mast cells linked to inflammation?

Lipid mediators such as leukotrienes or prostaglandins are also newly synthesized within a very short time and released into the surrounding tissue. New synthesis also occurs for growth factors and cytokines. The released histamine ultimately leads to the dilation and permeability of blood vessels and affects cell layers and nerves.

Symptoms include edema, skin rash, migraines, muscle pain, cold symptoms, diarrhea and constipation, and much more. The release of tryptase can also have a damaging effect on connective tissue cells as well as the intercellular substance. The contact between cells can no longer proceed smoothly. Instead, immune cells such as granulocytes (white blood cells) and goblet cells can be activated. An increased number of granulocytes can promote infections, inflammation, and chronic diseases such as rheumatoid arthritis.

Goblet cells produce mucus to ward off pathogens. However, overproduction can lead to breathing difficulties. Furthermore, mast cells secrete proinflammatory cytokines (inflammation-promoting polypeptides). These are significantly involved in inflammatory and immune reactions. With persistent allergen exposure, an inflammatory process can also become chronic.

What medications and therapies are available?

The most important therapy to calm mast cells is an elimination diet in the form of a low-histamine diet. Furthermore, there are (natural) mast cell stabilizers in the form of medications and foods (see below). Those who have been medically diagnosed with a mast cell disorder can receive mast cell stabilizers without additives by prescription.

Mast cells and a low-histamine diet

Can mast cells be influenced by diet? Indeed, there are certain foods that activate or even calm mast cells. Therefore, a low-histamine diet can reduce mast cell activity and allergic reactions. Natural low-histamine mast cell stabilizers are quercetin, curcumin, and luteolin. These include, for example, the following foods:

Apples
Blueberries
Celery
Red leaf lettuce
Onions
Asparagus
Red grapes
Broccoli
Capers
Turmeric
Carrots
Lettuce
Olive oil
Rosemary
Thyme
Oregano
Chamomile tea

However, there are also DAO inhibitors/HNMT inhibitors and foods that increasingly contribute to mast cell activation. These include histamine liberators, histamine-rich foods, and foods with biogenic amines such as

Organ meats
Cashews
Walnuts
Eggs
Shellfish
Avocado
Citrus fruits
Pineapple
Tomatoes
Alcohol
Cocoa
Sauerkraut
Aged cheese
Salami

Outlook on further research

Knowledge about mast cells still raises many questions within research. The topic of mast cell activation syndrome, in particular, is still far too under-researched. Even certain smells, such as fragrances, can trigger an anaphylactic shock in affected individuals. The association MCAS Hope, together with the University Hospital Aachen, Charité Berlin, and the FOM University of Applied Sciences Düsseldorf, has made it its mission to research mast cell activation syndrome using systems medicine as part of its scientific MAGELLAN study. From this, new insights into the disease are to be gained and new paths in therapy and diagnostics are to be identified.