Immune Equilibrium Depends on the Interaction Between Recognition and Presentation Landscapes

Shevyrev, Daniil; Tereshchenko, Valeriy; Козлов, В. А.

doi:10.3389/fimmu.2021.706136

Cited by 11 publications

(13 citation statements)

References 183 publications

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“…Modern immunology has become very complicated, involving complex theories and advanced technologies such as genomics (Neu et al, 2017), transcriptomics (Stubbington et al, 2017) and metabolomics (Everts, 2018). However, its core principle seems to be only the immune recognition theory (del Guercio, 1993;Janeway and Medzhitov, 2002;Kubelkova and Macela, 2019;Minervina et al, 2019;Joyce and Ternette, 2021;Werner et al, 2021), and the immune equilibrium theory (Swiatczak, 2014;Eberl, 2016;Cicchese et al, 2018;Shevyrev et al, 2021) is limited to the analysis of the philosophical significance of immune function. In this paper, I attempt to find an immunological theory like the simple laws of physics, and put forward the theoretical framework of immunodynamics to start the research in this novel field.…”

Section: Discussionmentioning

confidence: 99%

“…For example, Gerard Eberl proposes that immune equilibrium is a balance state achieved by the mutual inhibition of the three (or even four) different types of cellular immune responses mentioned above (Eberl, 2016). Recently, Daniil Shevyrev et al proposed that immune equilibrium highly depends on the interaction between antigen presentation and recognition, trying to unify the immune recognition theory and immune equilibrium theory (Shevyrev et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

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From immune equilibrium to immunodynamics

Chen

2022

Front. Microbiol.

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ObjectiveThe immunology field has long been short of a universally applicable theoretical model that can quantitatively describe the immune response, and the theory of immune equilibrium (balance) is usually limited to the interpretation of the philosophical significance of immune phenomena. Therefore, it is necessary to establish a new immunological theory, namely, immunodynamic theory, to reanalyze the immune response.MethodsBy quantifying the immune dynamic equilibrium as the ratio of positive and negative immune power, the immune dynamic equilibrium equation was established. Then, the area under the curve of the positive and negative immune power was assumed to be equal in the whole process of immune response (regardless of correct or not), and through thought experiments based on this key hypothesis, a series of new concepts and expressions were derived, to establish a series of immunodynamic equations.ResultsNew concepts of immune force and immune braking force and their expression equations, namely, the theoretical equations of immunodynamics, were derived through thought experiments, and the theoretical curves of immunodynamics were obtained according to these equations. Via the equivalent transformation of the theoretical equations and practical calculation of functional data, and by the methods of curve comparison and fitting, some practical equations of immunodynamics were established, and these practical equations were used to solve theoretical and practical problems that are related to the immunotherapy of infectious diseases and cancers.ConclusionThe traditional theory of immune equilibrium has been mathematized and transformed from a philosophical category into a new concrete scientific theory, namely the theory of immunodynamics, which solves the dilemma that the traditional theory cannot guide individualized medical practice for a long time. This new theory may develop into one of the core theories of immunology in the future.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

From immune equilibrium to immunodynamics

Chen

2022

Front. Microbiol.

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“…As a result, various TCR repertoires of CD4 + and CD8 + cells are formed that target the recognition of non-self antigens and can recognize self/altered-self with a high degree of precision. Besides, they provide self-tolerance due to a population of Treg cells with TCR repertoire that recognizes self-antigens [ 143 , 144 ]. In other words, the landscape of antigen presentation in the thymus plays a key role in the formation of landscapes for the recognition of T-cells and provides the “calibration” of TCR repertoires.…”

Section: The Role Of Aire In the Formation Of Tcr And Bcr Repertoiresmentioning

confidence: 99%

“…In other words, the landscape of antigen presentation in the thymus plays a key role in the formation of landscapes for the recognition of T-cells and provides the “calibration” of TCR repertoires. It is necessary so that the adaptive immune system could recognize self/altered-self and non-self, effectively eliminate non-self and altered-self antigens, and maintain self-tolerance [ 143 , 145 ]. It could be a significant advantage of the adaptive immunity of higher chordates in comparison with jawless vertebrates.…”

Section: The Role Of Aire In the Formation Of Tcr And Bcr Repertoiresmentioning

confidence: 99%

Phylogeny, Structure, Functions, and Role of AIRE in the Formation of T-Cell Subsets

Shevyrev

Tereshchenko

Козлов

et al. 2022

Cells

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It is well known that the most important feature of adaptive immunity is the specificity that provides highly precise recognition of the self, altered-self, and non-self. Due to the high specificity of antigen recognition, the adaptive immune system participates in the maintenance of genetic homeostasis, supports multicellularity, and protects an organism from different pathogens at a qualitatively different level than innate immunity. This seemingly simple property is based on millions of years of evolution that led to the formation of diversification mechanisms of antigen-recognizing receptors and later to the emergence of a system of presentation of the self and non-self antigens. The latter could have a crucial significance because the presentation of nearly complete diversity of auto-antigens in the thymus allows for the “calibration” of the forming repertoires of T-cells for the recognition of self, altered-self, and non-self antigens that are presented on the periphery. The central role in this process belongs to promiscuous gene expression by the thymic epithelial cells that express nearly the whole spectrum of proteins encoded in the genome, meanwhile maintaining their cellular identity. This complex mechanism requires strict control that is executed by several transcription factors. One of the most important of them is AIRE. This noncanonical transcription factor not only regulates the processes of differentiation and expression of peripheral tissue-specific antigens in the thymic medullar epithelial cells but also controls intercellular interactions in the thymus. Besides, it participates in an increase in the diversity and transfer of presented antigens and thus influences the formation of repertoires of maturing thymocytes. Due to these complex effects, AIRE is also called a transcriptional regulator. In this review, we briefly described the history of AIRE discovery, its structure, functions, and role in the formation of antigen-recognizing receptor repertoires, along with other transcription factors. We focused on the phylogenetic prerequisites for the development of modern adaptive immunity and emphasized the importance of the antigen presentation system.

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“…In the periphery, different functional types of dendritic cells [DCs ( 20 , 21 )] play an important role in coordinating the adaptive immune response ( 22 ). As pivotal regulators of immune homeostasis, plasmacytoid (pDCs) and conventional DCs (cDCs) have already been implicated in lupus ( 23 – 25 ), and CD8 + T-cell cross-tolerance through cDCs has been proposed as a fundamental mechanism in peripheral tissues to ensure antigenic tolerance ( 26 – 28 ).…”

Section: Introductionmentioning

confidence: 99%

Helios Expression Is Downregulated on CD8+ Treg in Two Mouse Models of Lupus During Disease Progression

París-Muñoz

Aizpurua²,

Barber³

2022

Front. Immunol.

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T-cell–mediated autoimmunity reflects an imbalance in this compartment that is not restored by tolerogenic immune cells, e.g., regulatory T cells or tolerogenic dendritic cells (tolDCs). Although studies into T-cell equilibrium have mainly focused on regulatory CD4+FoxP3+ T cells (CD4+ Tregs), recent findings on the lesser known CD8+ Tregs (CD44+CD122+Ly49+) have highlighted their non-redundant role in regulating lupus-like disease and their regulatory phenotype facilitated by the transcription factor Helios in mice and humans. However, there are still remaining questions about Helios regulation and dynamics in different autoimmune contexts. Here, we show the absence of CD8+ Tregs in two lupus-prone murine models: MRL/MPJ and MRL/lpr, in comparison with a non-prone mouse strain like C57BL/6. We observed that all MRL animals showed a dramatically reduced population of CD8+ Tregs and a greater Helios downregulation on diseased mice. Helios induction was detected preferentially on CD8+ T cells from OT-I mice co-cultured with tolDCs from C57BL/6 but not in MRL animals. Furthermore, the Helios profile was also altered in other relevant T-cell populations implicated in lupus, such as CD4+ Tregs, conventional CD4+, and double-negative T cells. Together, these findings could make Helios a versatile maker across the T-cell repertoire that is capable of differentiating lupus disease states.

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Immune Equilibrium Depends on the Interaction Between Recognition and Presentation Landscapes

Cited by 11 publications

References 183 publications

From immune equilibrium to immunodynamics

From immune equilibrium to immunodynamics

Phylogeny, Structure, Functions, and Role of AIRE in the Formation of T-Cell Subsets

Helios Expression Is Downregulated on CD8+ Treg in Two Mouse Models of Lupus During Disease Progression

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