scholarly journals Mathematical modelling of COVID-19 disease dynamics: Interaction between immune system and SARS-CoV-2 within host

2021 ◽  
Vol 7 (2) ◽  
pp. 2618-2633
Author(s):  
S. M. E. K. Chowdhury ◽  
◽  
J. T. Chowdhury ◽  
Shams Forruque Ahmed ◽  
Praveen Agarwal ◽  
...  
Keyword(s):  
Mathematical Model ◽  
Immune System ◽  
Natural Killer ◽  
Disease Severity ◽  
Immune Surveillance ◽  
Treatment Strategies ◽  
Vital Role ◽  
Sufficient Information ◽  
Disease Dynamics ◽  
Viral Therapy

<abstract><p>SARS-COV-2 (Coronavirus) viral growth kinetics within-host become a key fact to understand the COVID-19 disease progression and disease severity since the year 2020. Quantitative analysis of the viral dynamics has not yet been able to provide sufficient information on the disease severity in the host. The SARS-CoV-2 dynamics are therefore important to study in the context of immune surveillance by developing a mathematical model. This paper aims to develop such a mathematical model to analyse the interaction between the immune system and SARS-CoV-2 within the host. The model is developed to explore the viral load dynamics within the host by considering the role of natural killer cells and T-cell. Through analytical simplifications, the model is found well-posed and asymptotically stable at disease-free equilibrium. The numerical results demonstrate that the influx of external natural killer (NK) cells alone or integrating with anti-viral therapy plays a vital role in suppressing the SARS-CoV-2 growth within-host. Also, within the host, the virus can not grow if the virus replication rate is below a threshold limit. The developed model will contribute to understanding the disease dynamics and help to establish various potential treatment strategies against COVID-19.</p></abstract>

scholarly journals Human natural killer cells

Blood ◽  
2008 ◽  
Vol 112 (3) ◽  
pp. 461-469 ◽  
Author(s):  
Michael A. Caligiuri
Keyword(s):  
Immune System ◽  
Nk Cells ◽  
Natural Killer ◽  
Nk Cell ◽  
Immune Surveillance ◽  
Cell Receptor ◽  
Human Malignancy ◽  
Human Natural Killer Cells ◽  
Receptor Biology ◽  
Granular Lymphocytes

Abstract Natural killer (NK) cells were discovered more than 30 years ago. NK cells are large granular lymphocytes that belong to the innate immune system because unlike T or B lymphocytes of the adaptive or antigen-specific immune system, NK cells do not rearrange T-cell receptor or immunoglobulin genes from their germline configuration. During the past 2 decades there has been a substantial gain in our understanding of what and how NK-cells “see,” lending important insights into their functions and purpose in normal immune surveillance. The most recent discoveries in NK-cell receptor biology have fueled translational research that has led to remarkable results in treating human malignancy.

scholarly journals Glia–immune interactions post-ischemic stroke and potential therapies

2018 ◽  
Vol 243 (17-18) ◽  
pp. 1302-1312 ◽  
Author(s):  
Jessica Hersh ◽  
Shao-Hua Yang
Keyword(s):  
Ischemic Stroke ◽  
Immune System ◽  
Glial Cell ◽  
Glial Cells ◽  
Immune Cell ◽  
Immune Surveillance ◽  
Vital Role ◽  
Stroke Recovery ◽  
Therapeutic Window ◽  
Cns Injury

Although the primary responsibility of the immune system has for over a century been perceived as the protector of the host against infection in the peripheral organs, we now know the immune system also plays a vital role in recovery pathways associated with central nervous system (CNS) injury. There is mounting evidence that the blood–brain barrier does not preclude the CNS from immune surveillance. Of particular interest for this review is how microglia and astrocytes interact with the cells of the immune system to modulate repair and recovery mechanisms in ischemic stroke. Our review argues that by deepening our understanding of neuroimmunity, specifically the bidirectional glial–immune cell communications, a plethora of new therapeutic targets and mechanisms may be revealed. Consequently, this review instigates novel experimental approaches to neuroimmunology and fosters a more rapid discovery process for the treatment of stroke. Impact statement This article reviews glial cell interactions with the immune system post-ischemic stroke. Research has shown that glial cells in the brain play a role in altering phenotypes of other glial cells and have downstream immune cell targets ultimately regulating a neuroinflammatory response. These interactions may play a deleterious as well as beneficial role in stroke recovery. Furthermore, they may provide a novel way to approach potential therapies, since current stroke drug therapy is limited to only one Food and Drug Administration-approved drug complicated by a narrow therapeutic window. Until this point, most research has emphasized neuroimmune interactions, but little focus has been on bidirectional communication of glial–immune interactions in the ischemic brain. By expanding our understanding of these interactions through a compilation of glial cell effects, we may be able to pinpoint major modulating factors in brain homeostasis to maintain or discover ways to suppress irreversible ischemic damage and improve brain repair.

scholarly journals Aneuploid cells activate NF-κB to promote their immune clearance by NK cells

2020 ◽  
Author(s):  
Ruoxi W. Wang ◽  
Sonia Viganò ◽  
Uri Ben-David ◽  
Angelika Amon ◽  
Stefano Santaguida
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Nk Cells ◽  
Cancer Cells ◽  
Natural Killer ◽  
Nk Cell ◽  
Immune Surveillance ◽  
Immune Recognition ◽  
Immune Clearance

SummaryThe immune system plays a major role in the protection against cancer. Identifying and characterizing the pathways mediating this immune surveillance is thus critical for understanding how cancer cells are recognized and eliminated. We previously found that untransformed cells that had undergone senescence due to highly abnormal karyotypes are eliminated by Natural Killer (NK) cells in vitro. Here we show that this is also true for aneuploid untransformed cells that had not lost their ability to proliferate. Their elimination by NK cells, like that of aneuploid senescent cells, is predominantly mediated by non-cell autonomous mechanisms. Our data further indicate that NF-κB signaling in aneuploid cells is central to eliciting this immune response. Inactivating NF-κB abolishes NK-cell mediated clearance in aneuploid cells in vitro. In cancer cell lines, NF-κB signaling correlates with degree of aneuploidy, raising the possibility that aneuploidy-induced immune recognition is partially retained in cancer.

scholarly journals Harnessing the Immune System to Fight Multiple Myeloma

Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4546
Author(s):  
Jakub Krejcik ◽  
Mike Bogetofte Barnkob ◽  
Charlotte Guldborg Nyvold ◽  
Thomas Stauffer Larsen ◽  
Torben Barington ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Immune System ◽  
Clinical Care ◽  
Immune Surveillance ◽  
Treatment Strategies ◽  
Genetic Alterations ◽  
Response To Treatment ◽  
Immunosuppressive Tumor Microenvironment ◽  
And Function ◽  
New Strategies

Multiple myeloma (MM) is a heterogeneous plasma cell malignancy differing substantially in clinical behavior, prognosis, and response to treatment. With the advent of novel therapies, many patients achieve long-lasting remissions, but some experience aggressive and treatment refractory relapses. So far, MM is considered incurable. Myeloma pathogenesis can broadly be explained by two interacting mechanisms, intraclonal evolution of cancer cells and development of an immunosuppressive tumor microenvironment. Failures in isotype class switching and somatic hypermutations result in the neoplastic transformation typical of MM and other B cell malignancies. Interestingly, although genetic alterations occur and evolve over time, they are also present in premalignant stages, which never progress to MM, suggesting that genetic mutations are necessary but not sufficient for myeloma transformation. Changes in composition and function of the immune cells are associated with loss of effective immune surveillance, which might represent another mechanism driving malignant transformation. During the last decade, the traditional view on myeloma treatment has changed dramatically. It is increasingly evident that treatment strategies solely based on targeting intrinsic properties of myeloma cells are insufficient. Lately, approaches that redirect the cells of the otherwise suppressed immune system to take control over myeloma have emerged. Evidence of utility of this principle was initially established by the observation of the graft-versus-myeloma effect in allogeneic stem cell-transplanted patients. A variety of new strategies to harness both innate and antigen-specific immunity against MM have recently been developed and intensively tested in clinical trials. This review aims to give readers a basic understanding of how the immune system can be engaged to treat MM, to summarize the main immunotherapeutic modalities, their current role in clinical care, and future prospects.

Rapid COVID-19 Prognostic Blood Test for Disease Severity Using Epigenetic Immune System Biomarkers

2020 ◽  
Vol 6 (2) ◽  
pp. 26-29
Author(s):  
Adam G. Marsh ◽  
G. Mark Anderson ◽  
Erich J. Izdepski
Keyword(s):  
Immune System ◽  
Disease Severity ◽  
Blood Test

Novel Coronavirus SARS-CoV-2 (COVID-19) and Pregnancy: A hypothetical view

2020 ◽  
Vol 20 ◽  
Author(s):  
Ahmed RG
Keyword(s):  
Immune System ◽  
Cellular Therapy ◽  
Early Stage ◽  
Control Strategies ◽  
Vital Role ◽  
Healthy Life ◽  
Global Pandemic ◽  
Maternal Immune System ◽  
Perinatal Management ◽  
Novel Coronavirus

Background: The complications of the SARS-CoV-2 infection and its COVID-19 disease on mothers and their offspring are less known. Objective: The aim of this review was to determine the transmission, severity, complications of SARS-CoV-2 infection during the pregnancy. This review showed the influence of COVID-19 disease on the neonatal neurogenesis. Owing to no specific vaccines or medicines that were reported for the treatment of COVID-19 disease, this review suggested some control strategies like treatments (medicinal plants, antiviral therapy, cellular therapy, and immunotherapy), nutrition uptake, prevention, and recommendations. Discussion: This overview showed in severely states that SARS-CoV-2 infection during the early stage of pregnancy might increase the risk of stress, panic, and anxiety. This disorder can disturb the maternal immune system, and thus causing a neurodevelopmental disturbance. This hypothesis may be depending on the severity and intensity of the SARS-CoV-2 infection during pregnancy. However, vertical transmission of SARS-CoV-2 from dams to their fetuses is absent until now. Conclusion: During this global pandemic disease, maintaining safety during pregnancy, vaginal delivery, and breastfeeding may play a vital role in a healthy life for the offspring. Thus, international and national corporations should be continuing for perinatal management, particularly during the next pandemic or disaster time.

scholarly journals A Mathematical Model of Contact Tracing during the 2014–2016 West African Ebola Outbreak

Mathematics ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 608
Author(s):  
Danielle Burton ◽  
Suzanne Lenhart ◽  
Christina J. Edholm ◽  
Benjamin Levy ◽  
Michael L. Washington ◽  
...  
Keyword(s):  
Mathematical Model ◽  
Disease Management ◽  
Ebola Virus ◽  
Virus Disease ◽  
Infected Individual ◽  
Vital Role ◽  
West African ◽  
Contact Tracing ◽  
The Novel ◽  
Using Data

The 2014–2016 West African outbreak of Ebola Virus Disease (EVD) was the largest and most deadly to date. Contact tracing, following up those who may have been infected through contact with an infected individual to prevent secondary spread, plays a vital role in controlling such outbreaks. Our aim in this work was to mechanistically represent the contact tracing process to illustrate potential areas of improvement in managing contact tracing efforts. We also explored the role contact tracing played in eventually ending the outbreak. We present a system of ordinary differential equations to model contact tracing in Sierra Leonne during the outbreak. Using data on cumulative cases and deaths, we estimate most of the parameters in our model. We include the novel features of counting the total number of people being traced and tying this directly to the number of tracers doing this work. Our work highlights the importance of incorporating changing behavior into one’s model as needed when indicated by the data and reported trends. Our results show that a larger contact tracing program would have reduced the death toll of the outbreak. Counting the total number of people being traced and including changes in behavior in our model led to better understanding of disease management.

scholarly journals Disease severity-specific neutrophil signatures in blood transcriptomes stratify COVID-19 patients

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Anna C. Aschenbrenner ◽  
◽  
Maria Mouktaroudi ◽  
Benjamin Krämer ◽  
Marie Oestreich ◽  
...  
Keyword(s):  
Immune System ◽  
Disease Severity ◽  
Whole Blood ◽  
Viral Infections ◽  
Inflammatory Diseases ◽  
Target Prediction ◽  
Data Driven ◽  
Host Responses ◽  
Drug Candidates ◽  
Drug Target Prediction

Abstract Background The SARS-CoV-2 pandemic is currently leading to increasing numbers of COVID-19 patients all over the world. Clinical presentations range from asymptomatic, mild respiratory tract infection, to severe cases with acute respiratory distress syndrome, respiratory failure, and death. Reports on a dysregulated immune system in the severe cases call for a better characterization and understanding of the changes in the immune system. Methods In order to dissect COVID-19-driven immune host responses, we performed RNA-seq of whole blood cell transcriptomes and granulocyte preparations from mild and severe COVID-19 patients and analyzed the data using a combination of conventional and data-driven co-expression analysis. Additionally, publicly available data was used to show the distinction from COVID-19 to other diseases. Reverse drug target prediction was used to identify known or novel drug candidates based on finding from data-driven findings. Results Here, we profiled whole blood transcriptomes of 39 COVID-19 patients and 10 control donors enabling a data-driven stratification based on molecular phenotype. Neutrophil activation-associated signatures were prominently enriched in severe patient groups, which was corroborated in whole blood transcriptomes from an independent second cohort of 30 as well as in granulocyte samples from a third cohort of 16 COVID-19 patients (44 samples). Comparison of COVID-19 blood transcriptomes with those of a collection of over 3100 samples derived from 12 different viral infections, inflammatory diseases, and independent control samples revealed highly specific transcriptome signatures for COVID-19. Further, stratified transcriptomes predicted patient subgroup-specific drug candidates targeting the dysregulated systemic immune response of the host. Conclusions Our study provides novel insights in the distinct molecular subgroups or phenotypes that are not simply explained by clinical parameters. We show that whole blood transcriptomes are extremely informative for COVID-19 since they capture granulocytes which are major drivers of disease severity.

scholarly journals A mathematical model of tumor regression and recurrence after therapeutic oncogene inactivation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sharon S. Hori ◽  
Ling Tong ◽  
Srividya Swaminathan ◽  
Mariola Liebersbach ◽  
Jingjing Wang ◽  
...  
Keyword(s):  
Mathematical Model ◽  
Nk Cell ◽  
Tumor Regression ◽  
Lymphoblastic Leukemia ◽  
Immune Surveillance ◽  
Cancer Recurrence ◽  
Relative Number ◽  
Drug Resistant ◽  
Oncogene Addiction ◽  
Adoptive Therapy

AbstractThe targeted inactivation of individual oncogenes can elicit regression of cancers through a phenomenon called oncogene addiction. Oncogene addiction is mediated by cell-autonomous and immune-dependent mechanisms. Therapeutic resistance to oncogene inactivation leads to recurrence but can be counteracted by immune surveillance. Predicting the timing of resistance will provide valuable insights in developing effective cancer treatments. To provide a quantitative understanding of cancer response to oncogene inactivation, we developed a new 3-compartment mathematical model of oncogene-driven tumor growth, regression and recurrence, and validated the model using a MYC-driven transgenic mouse model of T-cell acute lymphoblastic leukemia. Our mathematical model uses imaging-based measurements of tumor burden to predict the relative number of drug-sensitive and drug-resistant cancer cells in MYC-dependent states. We show natural killer (NK) cell adoptive therapy can delay cancer recurrence by reducing the net-growth rate of drug-resistant cells. Our studies provide a novel way to evaluate combination therapy for personalized cancer treatment.

scholarly journals Natural Killer Cell Mobilization in Breast and Prostate Cancer Survivors: The Implications of Altered Stress Hormones Following Acute Exercise

Endocrines ◽  
2021 ◽  
Vol 2 (2) ◽  
pp. 121-132
Author(s):  
Erik D. Hanson ◽  
Lauren C. Bates ◽  
Kaileigh Moertl ◽  
Elizabeth S. Evans
Keyword(s):  
Prostate Cancer ◽  
Immune System ◽  
Cancer Survivors ◽  
Nk Cells ◽  
Natural Killer ◽  
Acute Exercise ◽  
Nk Cell ◽  
Killer Cell ◽  
Current Evidence ◽  
Cell Mobilization

Natural killer (NK) cells from the innate immune system are integral to overall immunity and also in managing the tumor burden during cancer. Breast (BCa) and prostate cancer (PCa) are the most common tumors in U.S. adults. Both BCa and PCa are frequently treated with hormone suppression therapies that are associated with numerous adverse effects including direct effects on the immune system. Regular exercise is recommended for cancer survivors to reduce side effects and improve quality of life. Acute exercise is a potent stimulus for NK cells in healthy individuals with current evidence indicating that NK mobilization in individuals with BCa and PCa is comparable. NK cell mobilization results from elevations in shear stress and catecholamine levels. Despite a normal NK cell response to exercise, increases in epinephrine are attenuated in BCa and PCa. The significance of this potential discrepancy still needs to be determined. However, alterations in adrenal hormone signaling are hypothesized to be due to chronic stress during cancer treatment. Additional compensatory factors induced by exercise are reviewed along with recommendations on standardized approaches to be used in exercise immunology studies involving oncology populations.

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