scholarly journals Mathematical Model of Antiviral Immune Response against the COVID-19 Virus

Mathematics ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1356
Author(s):  
Juan Carlos Chimal-Eguia
Keyword(s):  
Mathematical Model ◽  
Immune Response ◽  
Immune System ◽  
Adaptive Immune Response ◽  
Humoral Response ◽  
Antiviral Immune Response ◽  
Infection Dynamics ◽  
Current Outbreak ◽  
Delay Differential

This work presents a mathematical model to investigate the current outbreak of the coronavirus disease 2019 (COVID-19) worldwide. The model presents the infection dynamics and emphasizes the role of the immune system: both the humoral response as well as the adaptive immune response. We built a mathematical model of delay differential equations describing a simplified view of the mechanism between the COVID-19 virus infection and the immune system. We conduct an analysis of the model exploring different scenarios, and our numerical results indicate that some theoretical immunotherapies are successful in eradicating the COVID-19 virus.

scholarly journals Proteomic and metabolomic signatures associated with the immune response in healthy individuals immunized with an inactivated SARS-CoV-2 vaccine

2021 ◽  
Author(s):  
Yi Wang ◽  
Xiaoxia Wang ◽  
Laurence Don Wai Luu ◽  
Shaojin Chen ◽  
Jin Fu ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Systems Biology ◽  
Complement Activation ◽  
Metabolic Pathways ◽  
Molecular Mechanisms ◽  
Adaptive Immune Response ◽  
Humoral Response ◽  
Tca Cycle ◽  
Adaptive Immune

CoronaVac (Sinovac), an inactivated vaccine for SARS-CoV-2, has been widely used for immunization. However, analysis of the underlying molecular mechanisms driving CoronaVac-induced immunity is still limited. Here, we applied a systems biology approach to understand the mechanisms behind the adaptive immune response to CoronaVac in a cohort of 50 volunteers immunized with 2 doses of CoronaVac. Vaccination with CoronaVac led to an integrated immune response that included several effector arms of the adaptive immune system including specific IgM/IgG, humoral response and other immune response, as well as the innate immune system as shown by complement activation. Metabolites associated with immunity were also identified implicating the role of metabolites in the humoral response, complement activation and other immune response. Networks associated with the TCA cycle and amino acids metabolic pathways, such as phenylalanine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, and glycine, serine and threonine metabolism were tightly coupled with immunity. Critically, we constructed a multifactorial response network (MRN) to analyze the underlying interactions and compared the signatures affected by CoronaVac immunization and SARS-CoV-2 infection to further identify immune signatures and related metabolic pathways altered by CoronaVac immunization. These results suggest that protective immunity against SARS-CoV-2 can be achieved via multiple mechanisms and highlights the utility of a systems biology approach in defining molecular correlates of protection to vaccination.

scholarly journals Role of Circulating Lymphocytes in Patients with Sepsis

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Raul de Pablo ◽  
Jorge Monserrat ◽  
Alfredo Prieto ◽  
Melchor Alvarez-Mon
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Host Response ◽  
Adaptive Immune Response ◽  
Adaptive Immune ◽  
Potential Biomarker ◽  
Circulating Lymphocytes ◽  
Postmortem Studies

Sepsis is a systemic inflammatory response syndrome due to infection. The incidence rate is estimated to be up to 19 million cases worldwide per year and the number of cases is rising. Infection triggers a complex and prolonged host response, in which both the innate and adaptive immune response are involved. The disturbance of immune system cells plays a key role in the induction of abnormal levels of immunoregulatory molecules. Furthermore, the involvement of effector immune system cells also impairs the host response to the infective agents and tissue damage. Recently, postmortem studies of patients who died of sepsis have provided important insights into why septic patients die and showed an extensive depletion of CD4 and CD8 lymphocytes and they found that circulating blood cells showed similar findings. Thus, the knowledge of the characterization of circulating lymphocyte abnormalities is relevant for the understanding of the sepsis pathophysiology. In addition, monitoring the immune response in sepsis, including circulating lymphocyte subsets count, appears to be potential biomarker for predicting the clinical outcome of the patient. This paper analyzes the lymphocyte involvement and dysfunction found in patients with sepsis and new opportunities to prevent sepsis and guide therapeutic intervention have been revealed.

scholarly journals Impact of Zinc, Glutathione, and Polyphenols as Antioxidants in the Immune Response against SARS-CoV-2

Processes ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 506
Author(s):  
José Manuel Pérez de la Lastra ◽  
Celia Andrés-Juan ◽  
Francisco J. Plou ◽  
Eduardo Pérez-Lebeña
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Immune Responses ◽  
Rational Design ◽  
Global Scale ◽  
Key Factors ◽  
Central Function ◽  
Antiviral Immune Response ◽  
The Relationship

SARS-CoV-2, the coronavirus triggering the disease COVID-19, has a catastrophic health and socioeconomic impact at a global scale. Three key factors contribute to the pathogenesis of COVID-19: excessive inflammation, immune system depression/inhibition, and a set of proinflammatory cytokines. Common to these factors, a central function of oxidative stress has been highlighted. A diversity of clinical trials focused predominantly on antioxidants are being implemented as potential therapies for COVID-19. In this study, we look at the role of zinc, glutathione, and polyphenols, as key antioxidants of possible medicinal or nutritional significance, and examine their role in the antiviral immune response induced by SARS-Cov-2. An unresolved question is why some people experience chronic COVID and others do not. Understanding the relationship between SARS-CoV-2 and the immune system, as well as the role of defective immune responses to disease development, would be essential to recognize the pathogenesis of COVID-19, the risk factors that affect the harmful consequences of the disease, and the rational design of successful therapies and vaccinations. We expect that our research will provide a novel perspective that contributes to the design of clinical or nutritional targets for the prevention of this pandemic.

scholarly journals Protective Role of the Virus-Specific Immune Response for Development of Severe Neurologic Signs in Simian Immunodeficiency Virus-Infected Macaques

1998 ◽  
Vol 72 (12) ◽  
pp. 9940-9947 ◽  
Author(s):  
Sieghart Sopper ◽  
Ursula Sauer ◽  
Susanne Hemm ◽  
Monika Demuth ◽  
Justus Müller ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Simian Immunodeficiency Virus ◽  
Cognitive Disorders ◽  
Central Nervous System Disease ◽  
Protective Role ◽  
Antiviral Immune Response ◽  
Slow Progressors ◽  
Immunodeficiency Virus

ABSTRACT The pathogenesis of human immunodeficiency virus-associated motor and cognitive disorders is poorly understood. In this context both a protective and a harmful role of the immune system has been discussed. This question was addressed in the present study by correlating the occurrence of neurologic disease in simian immunodeficiency virus (SIV)-infected macaques with disease progression and the humoral and cellular intrathecal antiviral immune response. Overt neurologic signs consisting of ataxia and apathy were observed at a much higher frequency in rapid progressor animals (6 of 12) than in slow progressors (1 of 7). Whereas slow progressors mounted a strong antiviral antibody (Ab) response as evidenced by enzyme-linked immunosorbent and immunospot assays, neither virus-specific Ab titers nor Ab-secreting cells could be found in the cerebrospinal fluid (CSF) or brain parenchyma of rapid progressors. Similarly, increased infiltration of CD8+ T cells and cytotoxic T lymphocytes specific for viral antigens were detected only in the CSF of slow progressors. The finding that neurologic signs develop frequently in SIV-infected macaques in the absence of an antiviral immune response demonstrates that the immune system does not contribute to the development of motor disorders in these animals. Moreover, the lower incidence of neurologic symptoms in slow progressors with a strong intrathecal immune response suggests a protective role of the virus-specific immunity in immunodeficiency virus-induced central nervous system disease.

scholarly journals Role of Virally-Encoded Deubiquitinating Enzymes in Regulation of the Virus Life Cycle

2021 ◽  
Vol 22 (9) ◽  
pp. 4438
Author(s):  
Jessica Proulx ◽  
Kathleen Borgmann ◽  
In-Woo Park
Keyword(s):  
Immune Response ◽  
Life Cycle ◽  
Deubiquitinating Enzyme ◽  
Deubiquitinating Enzymes ◽  
Antiviral Immune Response ◽  
Cellular Processes ◽  
Virus Life Cycle ◽  
Infected Cells ◽  
Dependent Processes

The ubiquitin (Ub) proteasome system (UPS) plays a pivotal role in regulation of numerous cellular processes, including innate and adaptive immune responses that are essential for restriction of the virus life cycle in the infected cells. Deubiquitination by the deubiquitinating enzyme, deubiquitinase (DUB), is a reversible molecular process to remove Ub or Ub chains from the target proteins. Deubiquitination is an integral strategy within the UPS in regulating survival and proliferation of the infecting virus and the virus-invaded cells. Many viruses in the infected cells are reported to encode viral DUB, and these vial DUBs actively disrupt cellular Ub-dependent processes to suppress host antiviral immune response, enhancing virus replication and thus proliferation. This review surveys the types of DUBs encoded by different viruses and their molecular processes for how the infecting viruses take advantage of the DUB system to evade the host immune response and expedite their replication.

scholarly journals MITF induces escape from innate immunity in melanoma

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Luis Sánchez-del-Campo ◽  
Román Martí-Díaz ◽  
María F. Montenegro ◽  
Rebeca González-Guerrero ◽  
Trinidad Hernández-Caselles ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Nk Cells ◽  
Nk Cell ◽  
Luciferase Reporter ◽  
Damage Repair ◽  
Reporter Assays ◽  
Underlying Mechanisms ◽  
Nk Cytotoxicity

Abstract Background The application of immune-based therapies has revolutionized cancer treatment. Yet how the immune system responds to phenotypically heterogeneous populations within tumors is poorly understood. In melanoma, one of the major determinants of phenotypic identity is the lineage survival oncogene MITF that integrates diverse microenvironmental cues to coordinate melanoma survival, senescence bypass, differentiation, proliferation, invasion, metabolism and DNA damage repair. Whether MITF also controls the immune response is unknown. Methods By using several mouse melanoma models, we examine the potential role of MITF to modulate the anti-melanoma immune response. ChIP-seq data analysis, ChIP-qPCR, CRISPR-Cas9 genome editing, and luciferase reporter assays were utilized to identify ADAM10 as a direct MITF target gene. Western blotting, confocal microscopy, flow cytometry, and natural killer (NK) cytotoxicity assays were used to determine the underlying mechanisms by which MITF-driven phenotypic plasticity modulates melanoma NK cell-mediated killing. Results Here we show that MITF regulates expression of ADAM10, a key sheddase that cleaves the MICA/B family of ligands for NK cells. By controlling melanoma recognition by NK-cells MITF thereby controls the melanoma response to the innate immune system. Consequently, while melanoma MITFLow cells can be effectively suppressed by NK-mediated killing, MITF-expressing cells escape NK cell surveillance. Conclusion Our results reveal how modulation of MITF activity can impact the anti-melanoma immune response with implications for the application of anti-melanoma immunotherapies.

Immunotherapy: New insights in breast cancer treatment

2021 ◽  
pp. 1-10
Author(s):  
Bader Alshehri
Keyword(s):  
Breast Cancer ◽  
Immune Response ◽  
Immune System ◽  
Cancer Treatment ◽  
Immune Evasion ◽  
Breast Tumor ◽  
Parp Inhibitor ◽  
Breast Cancer Treatment ◽  
New Treatment

Breast cancer being the most malignant and lethal disease persistent among women globally. Immunotherapy as a new treatment modality has emerged in understanding the loopholes in the treatment of breast cancer which is mainly attributed to the potential of tumor cells to evade and survive the immune response by developing various strategies. Therefore, improved understanding of the immune evasion by cancer cells and the monoclonal antibodies against PD- and PD-L1 can help us in the diagnosis of this malignancy. Here in this article, I have highlighted that in addition to focusing on other strategies for breast cancer treatment, the involvement of immune system in breast cancer is vital for the understanding of this malignancy. Further, the complete involvement of immune system in the relapse or recurrence of the breast tumor and have also highlighted the role of vaccines, PD-1 and CTLA-4 with the recent advances in the field. Moreover, in addition to the application of immunotherapy as a sole therapy, combinations of immunotherapy with various strategies like targeting it with MEK inhibitors, Vaccines, chemotherapy and PARP inhibitor has shown to have significant benefits is also discussed in this article.

scholarly journals Current Concepts of Biliary Atresia and Matrix Metalloproteinase-7: A Review of Literature

2020 ◽  
Vol 7 ◽  
Author(s):  
Mark Nomden ◽  
Leonie Beljaars ◽  
Henkjan J. Verkade ◽  
Jan B. F. Hulscher ◽  
Peter Olinga
Keyword(s):  
Immune Response ◽  
Liver Fibrosis ◽  
Pulmonary Fibrosis ◽  
Matrix Metalloproteinase ◽  
Biliary Atresia ◽  
Adaptive Immune Response ◽  
Cell Contact ◽  
T Helper 1 ◽  
Matrix Metalloproteinase 7

Biliary atresia (BA) is a rare cholangiopathy of infancy in which the bile ducts obliterate, leading to profound cholestasis and liver fibrosis. BA is hypothesized to be caused by a viral insult that leads to over-activation of the immune system. Patients with BA are surgically treated with a Kasai portoenterostomy (KPE), which aims to restore bile flow from the liver to the intestines. After KPE, progressive liver fibrosis is often observed in BA patients, even despite surgical success and clearance of their jaundice. The innate immune response is involved during the initial damage to the cholangiocytes and further differentiation of the adaptive immune response into a T-helper 1 cell (Th1) response. Multiple studies have shown that there is continuing elevation of involved cytokines that can lead to the progressive liver fibrosis. However, the mechanism by which the progressive injury occurs is not fully elucidated. Recently, matrix metalloproteinase-7 (MMP-7) has been investigated to be used as a biomarker to diagnose BA. MMPs are involved in extracellular matrix (ECM) turnover, but also have non-ECM related functions. The role of MMP-7 and other MMPs in liver fibrosis is just starting to be elucidated. Multiple studies have shown that serum MMP-7 measurements are able to accurately diagnose BA in a cohort of cholestatic patients while hepatic MMP-7 expression correlated with BA-related liver fibrosis. While the mechanism by which MMP-7 can be involved in the pathophysiology of BA is unclear, MMP-7 has been investigated in other fibrotic pathologies such as renal and idiopathic pulmonary fibrosis. MMP-7 is involved in Wnt/β-catenin signaling, reducing cell-to-cell contact by shedding of E-cadherin, amplifying inflammation and fibrosis via osteopontin (OPN) and TNF-α while it also appears to play a role in induction of angiogenesis This review aims to describe the current understandings of the pathophysiology of BA. Subsequently, we describe how MMP-7 is involved in other pathologies, such as renal and pulmonary fibrosis. Then, we propose how MMP-7 can potentially be involved in BA. By doing this, we aim to describe the putative role of MMP-7 as a prognostic biomarker in BA and to provide possible new therapeutic and research targets that can be investigated in the future.

scholarly journals Haptoglobin and Its Related Protein, Zonulin—What Is Their Role in Spondyloarthropathy?

2021 ◽  
Vol 10 (5) ◽  
pp. 1131
Author(s):  
Magdalena Chmielińska ◽  
Marzena Olesińska ◽  
Katarzyna Romanowska-Próchnicka ◽  
Dariusz Szukiewicz
Keyword(s):  
Immune Response ◽  
Free Radicals ◽  
Immune System ◽  
Potential Role ◽  
Acute Phase Protein ◽  
Related Protein ◽  
Functional Differences ◽  
Phase Protein ◽  
Its Polymorphism

Haptoglobin (Hp) is an acute phase protein which supports the immune response and protects tissues from free radicals. Its concentration correlates with disease activity in spondyloarthropathies (SpAs). The Hp polymorphism determines the functional differences between Hp1 and Hp2 protein products. The role of the Hp polymorphism has been demonstrated in many diseases. In particular, the Hp 2-2 phenotype has been associated with the unfavorable course of some inflammatory and autoimmune disorders. Its potential role in modulating the immune system in SpA is still unknown. This article contains pathophysiological considerations on the potential relationship between Hp, its polymorphism and SpA.

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