Modern ideas about mechanisms of allergen-specific immunotherapy

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Abstract


Reviews of domestic and foreign authors consider different approaches to understanding the formation of immunological and clinical tolerance induced by allergen-specific immunotherapy (ASIT). Despite the wide variety of theoretical research, the mechanism of the body’s immune system’s response to ASIT remains unclear.

The aim of this review is to analyze the current understanding of the mechanisms of formation of changes in the body’s reactivity in response to an allergen after ASIT. It is known that the type of response to the antigen is determined by its dose. In low-dose ASIT tolerance to the antigen is formed in the absence of inflammation, which is apparently associated with the activation of specific high-affinity receptors on cells of the immune system. High doses of allergen in ASIT probably lead to a rearrangement of cellular receptors, causing a decrease in their number by internalization or a weakening of their sensitivity to an excessive signal (desensitization). Due to a decrease in the number of receptors and / or their loss of sensitivity, the response to the antigen changes according to the principle of negative regulation, implemented at the level of receptor or postreceptor mechanisms. The formation of an anti-inflammatory cytokine response to antigen contributes to the differentiation of naive T cells into inducible regulatory T cells (iTreg). The suppressing effect of Treg on immune system cells affects Th effector cells, mast cells, basophils, eosinophils, B cells, and dendritic cells.

The occurring immunological shifts form a new type of tolerant response to the allergen, namely, the change in the type of immunoglobulins from IgE to IgG and IgA and new phenotypes of T memory and B memory cells.


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About the authors

Stanislava Yu. Petrova

Mechnikov Research Institute of Vaccines and Sera

Author for correspondence.
Email: petrovastanislava@yandex.ru
ORCID iD: 0000-0003-3034-0148

Russian Federation, Moscow

Senior researcher of the Laboratory of Allergens, MD

Svetlana V. Khlgatian

Mechnikov Research Institute of Vaccines and Sera

Email: svetkh@gmail.com
ORCID iD: 0000-0001-8354-7682

Russian Federation, Moscow

Leading researcher of the Laboratory of Allergens, Doctor of Biological Sciences

Valentina М. Berzhets

Mechnikov Research Institute of Vaccines and Sera

Email: laball@yandex.ru
ORCID iD: 0000-0001-5055-7593

Russian Federation, Moscow

Head of the Laboratory of Allergens, professor

Nina S. Petrova

Mechnikov Research Institute of Vaccines and Sera

Email: s.levina2005@yandex.ru

Russian Federation, Moscow

Leading researcher of the Laboratory of Allergens, , Сandidate of Biological Sciences

Olga V. Radikova

Mechnikov Research Institute of Vaccines and Sera

Email: radikova@rambler.ru
ORCID iD: 0000-0001-9710-6968

Russian Federation, Moscow

Research fellow of the Laboratory of Allergens, MD

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Supplementary files

Supplementary Files Action
1.
Figure: 1. ASIT mechanisms by Jutel et al., 2016 [10]; Akdis et al., 2015 [7]

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2.
Figure: 2. Formation of immunological tolerance in ASIT according to Shamji and Durham, 2011 [12]. Repeated exposure to allergens in atopic-prone patients results in IgE-mediated allergic reactions. ASIT with high doses of the allergen leads to the induction of Tregs [adaptive Tregs (aTreg) and natural Tregs (nTreg)] and cytokines such as IL-10 and TGF-â. The release of cytokines plays an important role in suppressing Th2 reactions and contributes to the synthesis of allergen-specific antibodies of the IgA1, IgA2 and IgG4 isotypes, which have inhibitory activity. The ongoing immunological changes contribute to the physiological alignment of the Th2 / Th1 ratio due to a shift in differentiation towards Th1. The suppressive effect of Treg on cells of the immune system affects not only effector Th, but also mast cells, basophils, eosinophils, B cells, dendritic cells

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