self antigen
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Author(s):  
Rossella Della Marca ◽  
M. Piedade Ramos ◽  
Carolina Ribeiro ◽  
Ana Soares

Many autoimmune diseases are chronic in nature, so that in general patients experience periods of recurrence and remission of the symptoms characterizing their specific autoimmune ailment. In order to describe this very important feature of autoimmunity, we construct a mathematical model of kinetic type describing the immune system cellular interactions in the context of autoimmunity exhibiting recurrent dynamics. The model equations constitute a non-linear system of integro-differential equations with quadratic terms that describe the interactions between self-antigen presenting cells, self-reactive T cells and immunosuppressive cells. We consider a constant input of self-antigen presenting cells, due to external environmental factors that are believed to trigger autoimmunity in people with predisposition for this condition. We also consider the natural death of all cell populations involved in our model, caused by their interaction with cells of the host environment. We derive the macroscopic analogue and show positivity and well-posedness of the solution, and then we study the equilibria of the corresponding dynamical system and their stability properties. By applying dynamical system theory, we prove that steady oscillations may arise due to the occurrence of a Hopf bifurcation. We perform some numerical simulations for our model, and we observe a recurrent pattern in the solutions of both the kinetic description and its macroscopic analogue, which leads us to conclude that this model is able to capture the chronic behaviour of many autoimmune diseases.


eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Logan K Smith ◽  
Kareem Fawaz ◽  
Bebhinn Treanor

Despite the mechanisms of central and peripheral tolerance, the mature B cell compartment contains cells reactive for self-antigen. How these cells are poised not to respond and the mechanisms that restrain B cell responses to low-affinity endogenous antigens are not fully understood. Here, we demonstrate a critical role for the glycan-binding protein galectin-9 in setting the threshold of B cell activation and that loss of this regulatory network is sufficient to drive spontaneous autoimmunity. We further demonstrate a critical role for galectin-9 in restraining not only conventional B-2 B cells, but also innate-like B-1a cells. We show that galectin-9-deficient mice have an expanded population of B-1a cells and increased titers of B-1a-derived autoantibodies. Mechanistically, we demonstrate that galectin-9 regulates BCR and distinct TLR responses in B-1a cells, but not B-1b cells, by regulating the interaction between BCR and TLRs with the regulatory molecules CD5 and CD180, respectively. In the absence of galectin-9, B-1a cells are more readily activated and secrete increased titers of autoantibodies that facilitate autoantigen delivery to the spleen, driving autoimmune responses.


2021 ◽  
Vol 6 (62) ◽  
pp. eabg9433
Author(s):  
Shiyue Hou ◽  
Tiange Shao ◽  
Tianyang Mao ◽  
Jingwen Shi ◽  
Jiahui Sun ◽  
...  

A primary immune response is initiated in secondary lymphoid organs. Virtual memory CD8+ T (TVM) cells are antigen-inexperienced T cells of a central memory phenotype, acquired through self-antigen–driven homeostatic proliferation. Unexpectedly, we find that TVM cells are composed of CCR2+ and CCR2− subsets that differentially elaborate a spectrum of effector- and memory-poised functions directly in the tissue. During a primary influenza infection, TVM cells rapidly infiltrate the lungs in the first day after infection and promote early viral control. TVM cells that recognize viral antigen are retained in the tissue, clonally expand independent of secondary lymphoid organs, and give rise to tissue-resident memory cells. By orchestrating an extralymphoid primary response, heterogenous TVM cells bridge innate reaction and adaptive memory directly in the infected tissue.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Sandra S. Ring ◽  
Jovana Cupovic ◽  
Lucas Onder ◽  
Mechthild Lütge ◽  
Christian Perez-Shibayama ◽  
...  

AbstractThe tumor microenvironment (TME) is a complex amalgam of tumor cells, immune cells, endothelial cells and fibroblastic stromal cells (FSC). Cancer-associated fibroblasts are generally seen as tumor-promoting entity. However, it is conceivable that particular FSC populations within the TME contribute to immune-mediated tumor control. Here, we show that intratumoral treatment of mice with a recombinant lymphocytic choriomeningitis virus-based vaccine vector expressing a melanocyte differentiation antigen resulted in T cell-dependent long-term control of melanomas. Using single-cell RNA-seq analysis, we demonstrate that viral vector-mediated transduction reprogrammed and activated a Cxcl13-expressing FSC subset that show a pronounced immunostimulatory signature and increased expression of the inflammatory cytokine IL-33. Ablation of Il33 gene expression in Cxcl13-Cre-positive FSCs reduces the functionality of intratumoral T cells and unleashes tumor growth. Thus, reprogramming of FSCs by a self-antigen-expressing viral vector in the TME is critical for curative melanoma treatment by locally sustaining the activity of tumor-specific T cells.


2021 ◽  
Author(s):  
Salome Glauzy ◽  
Brennan Olson ◽  
Christopher K. May ◽  
Daniele Parisi ◽  
Christopher Massad ◽  
...  

2021 ◽  
pp. 22-28
Author(s):  
Indira Ananthapadmanab asamy ◽  
G. Rajaram ◽  
C.H.Srinivasa Rao

Introduction: Autoimmunity is a condition in which the body's own cells which are immunocompetent and the antibodies, acts against its own self-antigen which will result in structural and functional damage to the body. The diseases caused by this phenomenon are called Autoimmune diseases. Autoimmune diseases are more commonly seen in females. Hundred thousands of individuals in the Western countries are affected. The diagnosis is made from the clinical presentation of the patient with which a differential diagnosis is made, following which various tests both phenotyping methods and genotyping methods are carried out to conclude the nal diagnosis. Conclusion: The genotyping methods play the most important role in the laboratory diagnosis of systemic immune diseases.


Author(s):  
David D. Roberts ◽  
Jeffrey S. Isenberg

Thrombospondin-1 (TSP1) is the prototypical member of a family of secreted proteins that modulate cell behavior by engaging with molecules in the extracellular matrix and with receptors on the cell surface. CD47 is widely displayed on many, if not all, cell types and is a high affinity TSP1 receptor. CD47 is a self-antigen that limits innate immune cell activities, a feature recently exploited to enhance cancer immunotherapy. Another major role for CD47 in health and disease is to mediate TSP1 signaling. TSP1 acting through CD47 contributes to mitochondrial, metabolic and endocrine dysfunction. Studies in animal models found that elevated TSP1 expression, acting in part through CD47, causes mitochondrial and metabolic dysfunction. Clinical studies established that abnormal TSP1 expression positively correlates with obesity, fatty liver disease and diabetes. The unabated increase in these conditions worldwide and the availability of CD47 targeting drugs justify a closer look into how TSP1 and CD47 disrupt metabolic balance and the potential for therapeutic intervention.


2021 ◽  
Author(s):  
Francine Padonou ◽  
Virginie Gonzalez ◽  
Nada Jmari ◽  
Julia Maslovskaja ◽  
Kai Kisand ◽  
...  

AbstractAire allows medullary thymic epithelial cells (mTECs) to express and present a large number of self-antigens for central tolerance. Although mTECs express a high diversity of self-antigen splice isoforms, the extent and regulation of alternative splicing events (ASEs) included in their transcripts, notably in those induced by Aire, is unknown. Unexpectedly, and in contrast to Aire-neutral genes, we found that the Aire-sensitive genes exhibit in Aire-positive and negative mTECs, a weak inclusion of ASEs, with about a quarter present in peripheral tissues being excluded from the thymus. We identified Raver2, as a splicing-related factor overrepresented in mTECs and dependent on H3K36me3 marks. We discovered that both Raver2 and methylation of H3K36 promoted ASE inclusion for Aire-neutral genes, leaving Aire-sensitive genes unaffected. Profiling of H3K36me3 revealed its depletion at Aire-sensitive genes, supporting a mechanism, whose setup precedes Aire’s expression and by which Aire-sensitive genes exhibit weak ASE inclusion through the escape of Raver2’s effect. Lack of ASEs in Aire-induced transcripts highlights a role for regulatory T cells in controlling the incomplete Aire-dependent negative selection.


Entropy ◽  
2021 ◽  
Vol 23 (4) ◽  
pp. 405
Author(s):  
Sheri M. Markose

This paper gives formal foundations and evidence from gene science in the post Barbara McClintock era that the Gödel Sentence, far from being an esoteric construction in mathematical logic, is ubiquitous in genomic intelligence that evolved with multi-cellular life. Conditions uniquely found in the Adaptive Immune System (AIS) and Mirror Neuron System (MNS), termed the genomic immuno-cognitive system, coincide with three building blocks in computation theory of Gödel, Turing and Post (G-T-P). (i) Biotic elements have unique digital identifiers with gene codes executing 3D self-assembly for morphology and regulation of the organism using the recursive operation of Self-Ref (Self-Reference) with the other being a self-referential projection of self. (ii) A parallel offline simulation meta/mirror environment in 1–1 relation to online machine executions of self-codes gives G-T-P Self-Rep (Self-Representation). (iii) This permits a digital biotic entity to self-report that it is under attack by a biotic malware or non-self antigen in the format of the Gödel sentence, resulting in the “smarts” for contextual novelty production. The proposed unitary G-T-P recursive machinery in AIS and in MNS for social cognition yields a new explanation that the Interferon Gamma factor, known for friend-foe identification in AIS, is also integral to social behaviors. New G-T-P bio-informatics of AIS and novel anti-body production is given with interesting testable implications for COVID-19 pathology.


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