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Allergen Tolerance – Immune System and Allergies

Allergen tolerance is the ability of the immune system to not overreact to harmless substances. It forms the basis of modern treatments such as allergen immunotherapy.

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Things worth knowing about "Allergen Tolerance"

Allergen tolerance is the ability of the immune system to not overreact to harmless substances. It forms the basis of modern treatments such as allergen immunotherapy.

What Is Allergen Tolerance?

Allergen tolerance refers to the state in which the immune system does not mount an excessive response to certain substances known as allergens. In healthy individuals, natural tolerance exists toward most environmental and dietary substances. In people with allergies, this tolerance is disrupted, causing the immune system to treat harmless substances such as pollen, animal dander, or food proteins as threats, triggering an allergic reaction.

Immunological Basis

Allergen tolerance is based on complex immune mechanisms. Key components include:

Regulatory T cells (Tregs): These specialized immune cells suppress excessive immune responses and promote tolerance to allergens.
IgG4 antibodies: As tolerance develops, increased levels of immunoglobulin G4 antibodies are produced, which act in a blocking manner and reduce allergic reactions.
Interleukin-10 (IL-10): This anti-inflammatory signaling molecule is increasingly released during tolerance development and inhibits the release of inflammatory mediators.

Causes of Impaired Allergen Tolerance

Why some people develop allergies and others do not is not yet fully understood. Known contributing factors include:

Genetic predisposition: A family history of atopic conditions significantly increases the risk of developing allergies.
Hygiene hypothesis: Insufficient exposure to microorganisms during early childhood may impair the development of tolerance.
Environmental factors: Air pollution, tobacco smoke, and changing living conditions negatively affect the immune system.
Early childhood diet: Introducing certain foods too late or too early can interfere with the development of oral tolerance.

Oral Tolerance

A particularly important area is oral tolerance – the ability of the immune system not to react to food components with an allergic response. It develops primarily in early childhood through repeated exposure to dietary proteins via the gastrointestinal tract. If this tolerance is not established, a food allergy may develop.

Allergen Immunotherapy to Restore Tolerance

The most important medical method for actively promoting allergen tolerance is allergen immunotherapy (AIT), also known as desensitization or hyposensitization. The patient is given gradually increasing doses of the triggering allergen to accustom the immune system to the substance and build lasting tolerance. The main forms include:

Subcutaneous immunotherapy (SCIT): The allergen is injected under the skin.
Sublingual immunotherapy (SLIT): The allergen is administered as drops or tablets placed under the tongue.
Oral immunotherapy (OIT): Primarily used for food allergies, where the allergen is consumed by mouth.

Successful immunotherapy can permanently reduce symptoms and, in the best cases, achieve complete tolerance to the allergen.

Diagnosis

Several diagnostic methods are used to assess allergen tolerance:

Skin prick test and intradermal test: Skin reaction tests to identify specific allergens.
Specific IgE blood test: Measurement of allergen-specific antibodies in the blood.
Oral provocation test: Controlled administration of the allergen under medical supervision.
Basophil activation test (BAT): A functional test to evaluate the immune response.

Relevance for Prevention

Understanding allergen tolerance is of great importance for allergy prevention. Recent studies show that early exposure to certain allergens – especially in infants – can prevent the development of food allergies. Current guidelines recommend the early introduction of peanut and egg products in high-risk infants to promote oral tolerance.

References

Akdis, C.A. & Akdis, M. (2015). Mechanisms of allergen-specific immunotherapy and immune tolerance to allergens. World Allergy Organization Journal, 8(1), 17. PubMed PMID: 26023320.
Du Toit, G. et al. (2015). Randomized Trial of Peanut Consumption in Infants at Risk for Peanut Allergy (LEAP Study). New England Journal of Medicine, 372(9), 803–813.
European Academy of Allergy and Clinical Immunology (EAACI). Allergen Immunotherapy Guidelines (2023). Available at: www.eaaci.org

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