Medical Immunology Commons^™

The Effects Of E-Vapor On The Pathogenesis Of Rheumatoid Arthritis Mouse Models And Potential Implications For Future Generations, Christiana Daas

Selected Honors Theses

Rheumatoid arthritis is the most prevalent autoimmune disease. Rheumatoid arthritis (RA) has no cure, and the direct cause of the disease is still unknown. The two leading hypotheses concerning its etiology are based on the effects of HLA-DRB1 gene expression, and cigarette smoke. Conjunctively, the use of vaping devices amongst adolescents has increased significantly since introduced in 2007. There is no long-term data on the effects of e-vapor and its aerosols on bodily health. Cigarette smoke is the most noteworthy environmental factor contributing to RA therefore the question is raised as to whether or not vaping relates to rheumatoid arthritis …

Immunohistochemical Pattern– A Prognostic Factor For Synchronous Gastrointestinal Cancer, Catalin Alius, Catalin Gabriel Cirstoveanu, Cristinel Dumitru Badiu, Valeriu Ardeleanu, Vasile Adrian Dumitru

Journal of Mind and Medical Sciences

Recent advancements in medical genetics and molecular biology are reflected in the modern understanding and approach to colorectal carcinoma (CRC). Understanding the cellular mechanisms and mutational patterns that promote carcinogenesis could enhance the predictive accuracy of the TNM classification. Furthermore, this will allow for a much more documented stratification and tailored oncological treatment. This paper presents an illustrative case of a relatively young patient (50 years old) with no family history of cancer who was diagnosed with four synchronous gastrointestinal (GI) adenocarcinomas displaying a wild type P53, negative BRAF testing, and mutated MLH1 and PMS2 proteins. This case report contributes …

A Functional K+ Channel From Tetraselmis Virus 1, A Member Of The Mimiviridae, Kerri Kukovetz, Brigitte Hertel, Christopher R. Schvarcz, Andrea Saponaro, Mirja Manthey, Ulrike Burk, Timo Greiner, Grieg F. Steward, James L. Van Etten, Anna Moroni, Gerhard Thiel, Oliver Rauh

Nebraska Center for Virology: Faculty Publications

Potassium ion (K+) channels have been observed in diverse viruses that infect eukaryotic marine and freshwater algae. However, experimental evidence for functional K+ channels among these alga-infecting viruses has thus far been restricted to members of the family Phycodnaviridae, which are large, double-stranded DNA viruses within the phylum Nucleocytoviricota. Recent sequencing projects revealed that alga-infecting members of Mimiviridae, another family within this phylum, may also contain genes encoding K+ channels. Here we examine the structural features and the functional properties of putative K+ channels from four cultivated members of Mimiviridae. While all four proteins contain variations …

Neutrophil: A New Player In Metastatic Cancers, Mengyue Wu, Mutian Ma, Zhenya Tan, Hong Zheng, Xia Liu

Toxicology and Cancer Biology Faculty Publications

The interaction between cancer cells and immune cells is important for the cancer development. However, much attention has been given to T cells and macrophages. Being the most abundant leukocytes in the blood, the functions of neutrophils in cancer have been underdetermined. They have long been considered an “audience” in the development of cancer. However, emerging evidence indicate that neutrophils are a heterogeneous population with plasticity, and subpopulation of neutrophils (such as low density neutrophils, polymorphonuclear-myeloid-derived suppressor cells) are actively involved in cancer growth and metastasis. Here, we review the current understanding of the role of neutrophils in cancer development, …

A Novel Methodology To Identify The Primary Topics Contained Within The Covid-19 Research Corpus, Allen Crane, Brock Freidrich, William Fehlman, Igor Frolow, Daniel W. Engels

SMU Data Science Review

In this paper, we present a novel framework and system for the identification of primary research topics from within a corpus of related publications, the classification of individual publications according to these topics, and the results of the application of our framework and system to the COVID-19 Open Research Dataset (CORD-19). CORD-19 is a corpus of published peer reviewed and pre-peer reviewed articles related to the coronavirus that causes COVID-19. Using machine learning techniques, such as Non-negative Matrix Factorization for Natural Language Processing and a Bayesian classifier, we developed a novel framework and system that automatically extracts sparse and meaningful …

Hdac6 Mediates Macrophage Inos Expression And Excessive Nitric Oxide Production In The Blood During Endotoxemia, Yan Wang, Ke Wang, Jian Fu

Toxicology and Cancer Biology Faculty Publications

Excessive nitric oxide (NO) production and NO-mediated nitrative stress contribute to vascular dysfunction, inflammation, and tissue injury in septic shock. New therapeutic targets are urgently needed to provide better control of NO level during septic shock. In the present study, we investigated the role of HDAC6 in the regulation of NO production and nitrative stress in a mouse model of endotoxin-induced septic shock. HDAC6 deficient mice and a specific HDAC6 inhibitor were utilized in our studies. Our data clearly indicate that HDAC6 is an important mediator of NO production in macrophages. HDAC6 mediates NO production through the regulation of iNOS …

The Great Debate At 'Immunotherapy Bridge', Naples, December 5, 2019., Paolo A Ascierto, Carlo Bifulco, Jerome Galon, Claus Garbe, Samir N Khleif, Jennifer Mcquade, Kunle Odunsi, Hideho Okada, Chrystal M Paulos, Sergio A Quezada, Hussein A Tawbi, John Timmerman, Giorgio Trinchieri, Lisa H Butterfield, Igor Puzanov

Articles, Abstracts, and Reports

As part of the 2019 Immunotherapy Bridge congress (December 4-5, Naples, Italy), the Great Debate session featured counterpoint views from leading experts on six topical issues in immunotherapy today. These were the use of chimeric antigen receptor T cell therapy in solid tumors, whether the Immunoscore should be more widely used in clinical practice, whether antibody-dependent cellular cytotoxicity is important in the mode of action of anticytotoxic T-lymphocyte-associated protein 4 antibodies, whether the brain is immunologically unique or just another organ, the role of microbiome versus nutrition in affecting responses to immunotherapy, and whether chemotherapy is immunostimulatory or immunosuppressive. Discussion …

Plasmodium Impairs Antibacterial Innate Immunity To Systemic Infections In Part Through Hemozoin-Bound Bioactive Molecules., Christopher Lynn Harding

Electronic Theses and Dissertations

Despite efforts to decrease the global health burden of malaria, infections with Plasmodium species continue to cause over 200 million episodes of malaria each year which resulted in 405,000 deaths in 2018 [1]. One complication of malaria is increased susceptibility to invasive bacterial infections. Plasmodium infections impair host immunity to non-Typhoid Salmonella (NTS) through activities of heme oxygenase I (HO-I) )-induced release of immature granulocytes and myeloid cell-derived IL-10. Yet, it is not known if these mechanisms are specific to NTS. We show here, that Plasmodium yoelii 17XNL (Py) infected mice had impaired clearance of systemic Listeria monocytogenes (Lm) during …

Development, Expansion And Role Of Myeloid-Derived Suppressor Cells In Post-Sepsis Immune Suppression, Tuqa Alkhateeb

Electronic Theses and Dissertations

Myeloid-derived suppressor cells (MDSCs) numbers increase significantly in sepsis and are associated with high mortality rates. These myeloid cell precursors promote immunosuppression, especially in the late (post sepsis) stage. However, the mechanisms that underlie MDSC expansion and programming are not completely understood. To investigate these mechanisms, we used a cecal-ligation and puncture (CLP) mouse model of polymicrobial sepsis that progresses from an early/acute proinflammatory phase to a late/chronic immunosuppressive phase. Previous studies in our laboratory showed that microRNA (miR)-21 and miR-181b elevate levels of the transcription factor nuclear factor 1 (NFI-A) that promotes MDSC expansion. We report here that miR-21 …

Tumor-Derived Exosomes Drive Immunosuppressive Macrophages In A Pre-Metastatic Niche Through Nf-Kβ Dependent Glycolytic Metabolic Reprogramming., Samantha M. Morrissey

Electronic Theses and Dissertations

The formation of a pre-metastatic niche is a fundamental requirement for primary tumor metastasis. One of the defining characteristics of a pre-metastatic niche is infiltration of immunosuppressive macrophages. However, how these macrophages acquire their immunosuppressive phenotype remains largely unexplored. Here, we demonstrate that tumor-derived exosomes (TDE) polarize macrophages towards an immunosuppressive phenotype characterized by increased PD-L1 expression through NF-kB-dependent metabolic reprogramming in mice and humans. While NF-κB has previously been shown to act as a direct transcription factor for PD-L1, we report a novel mechanism where TDE-induced NF-κB activation drives PD-L1 expression by augmenting the glycolytic capacity of macrophages through …

Cell Cycle Regulation In Macrophages And Susceptibility To Hiv-1, Isabella A. T. M. Ferreira, James Zachary Porterfield, Ravindra K. Gupta, Petra Mlcochova

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Macrophages are the first line of defence against invading pathogens. They play a crucial role in immunity but also in regeneration and homeostasis. Their remarkable plasticity in their phenotypes and function provides them with the ability to quickly respond to environmental changes and infection. Recent work shows that macrophages undergo cell cycle transition from a G0/terminally differentiated state to a G1 state. This G0-to-G1 transition presents a window of opportunity for HIV-1 infection. Macrophages are an important target for HIV-1 but express high levels of the deoxynucleotide-triphosphate hydrolase SAMHD1, which restricts viral DNA synthesis by decreasing levels of dNTPs. While …

Veterans Helping Veterans Mid-Day Talk: Gulf War Illness Research, Bill Watts, Elizabeth G. Balbin

INIM Research Seminar Series

• Meet the Gulf War Illness Research Team.
• Learn about the ease of participating in research.
• Hear from veterans who have participated in research.
• Learn about different studies currently available.

Convalescent Plasma In Covid-19, Ranjit S. Banwait, Joshua K. Salabei, Troy J. Fishman, Uma G. Iyer

HCA Healthcare Journal of Medicine

The recent pandemic of SARS-CoV-2, which causes novel coronavirus disease 2019 (Covid-19), has had devastating impact on a global and national scale. In order to overcome this outbreak it is imperative we find treatments that are safe and effective. To date, no definitive treatment is available that can curtail the spread of this viral syndrome. Convalescent plasma (CP) is one such option that has repeatedly served as an important tool in treatment of various bacterial and viral infections, especially in the setting of no specific antimicrobial or vaccination against an infectious disease. Herein, we review the history of CP, prior …

Multi-Omics: Differential Expression Of Ifn-Γ Results In Distinctive Mechanistic Features Linking Chronic Inflammation, Gut Dysbiosis, And Autoimmune Diseases, Heekyong R. Bae, Patrick S. C. Leung, Deborah L. Hodge, John M. Fenimore, Seon Min Jeon, Vishal Thovarai, Amiran Dzutsev, Andrew A. Welcher, Michael Boedigheimer, Michael A. Damore, Myung Sook Choi, Richard A. Fravell, Giorgio Trinchieri, M. Eric Gershwin, Howard A. Young

United States Public Health Resources

Low grade, chronic inflammation is a critical risk factor for immunologic dysfunction including autoimmune diseases. However, the multiplicity of complex mechanisms and lack of relevant murine models limit our understanding of the precise role of chronic inflammation. To address these hurdles, we took advantage of multi-omics data and a unique murine model with a low but chronic expression of IFN-γ, generated by replacement of the AU-rich element (ARE) in the 3’ UTR region of IFN-γ mRNA with random nucleotides. Herein, we demonstrate that low but differential expression of IFN-γ in mice by homozygous or heterozygous ARE replacement triggers distinctive gut …

Epstein Barr Virus-Immortalizedｂlymphocytes Exacerbate Experimental Autoimmune Encephalomyelitis In Xenograft Mice, Pascal Polepole, Alison Bartenslager, Yutong Liu, Thomas M. Petro, Samodha C. Fernando, Luwen Zhang

Nebraska Center for Virology: Faculty Publications

Multiple sclerosis (MS) is the most common autoimmune disorder affecting the central nervous system. Epstein-Barr virus (EBV) is a causative agent for infectious mononucleosis (IM) that is associated with MS pathogenesis. However, the exact mechanism by which EBV, specifically in IM, increases the risk for MS remains unknown. EBV immortalizes primary B lymphocytes in vitro and causes excessive B lymphocyte proliferation in IM in vivo. In asymptomatic carriers, EBV-infected B lymphocytes still proliferate to certain degrees, the process of which is tightly controlled by the host immune systems. Experimental autoimmune encephalomyelitis (EAE) mimics key features of MS in humans …

Frequency Of Monocyte Subsets Is Linked To The Severity Of Atherosclerosis In Patients With Ischemic Heart Disease: A Case-Control Study, Irina V. Kologrivova, Tatiana Suslova, Olga Koshelskaya, Oksana Trubacheva, Olga Haritonova, Irina Vinnitskaya

BioMedicine

Background: Monocytes are recognized as central cells in the progression of atherosclerosis, and are subcategorized into classical (CD14++CD16^lo), intermediate (CD14++CD16^hi) and non-classical (CD14+CD16^hi) subsets.

Purpose: The present study aimed to assess the relationships between different subsets of monocytes, metabolic and inflammatory factors in patients with stable coronary heart disease.

Methods: A total of 26 patients (both men and women) with stable ischemic heart disease (IHD). Among all the recruited patients, 17 patients had significant coronary artery disease defined as diameter stenosis more than 70%. Severity of CHD was assessed by the Gensini score (GS). …

Correlation Of Inflammation In Arthritis With The Myelination In The Brain, Anna Spears

Honors Theses

This study was conducted to investigate whether the influence of arthritis has an effect on the cerebral white matter. The project was performed at the South Oxford Campus, where diffusion tensor imaging (DTI) data was obtained from the Nathan Kline Institute-Rockland Sample (NKI- RS). Image processing was conducted using Functional Magnetic Resonance Imaging of Brain Software Library in which we obtained raw data to formulate Apparent Diffusion Coefficient (ADC), Axial Diffusivity (AD), Radial Diffusivity (RD), and Fractional Anisotropy. A one way Analysis of Covariance (ANCOVA) was performed to determine the significant difference between the history of arthritis on each of …

Transient Display Of Chimeric Proteins On Biological Surfaces As An Effective Strategy For Modulations Of Innate And Adaptive Immune Responses., Pradeep Shrestha

Electronic Theses and Dissertations

The major premise of this dissertation was to transiently display novel immunological ligands on biological membranes as a localized means of modulating innate and adaptive immune responses with applications to bone marrow and pancreatic islet transplantation. In Chapter two, we engineered donor allogeneic bone marrow cells to transiently display a novel form of FasL, SA-FasL, to efficiently purge out alloreactive donor T cells to prevent acute GVHD. In Chapter three, we engineered pancreatic islets with a novel form of CD47, SA-CD47, to modulate instant blood mediated inflammatory reaction (IBMIR) to prevent immediate islet graft loss following intraportal transplantation. GVHD is …

Targeting Natural Killer Cells For Improved Immunity And Control Of The Adaptive Immune Response., Stephen Pierce, Eric S. Geanes, Todd Bradley

Manuscripts, Articles, Book Chapters and Other Papers

Natural killer (NK) cells are critical for targeting and killing tumor, virus-infected and stressed cells as a member of the innate immune system. Recently, NK cells have also emerged as key regulators of adaptive immunity and have become a prominent therapeutic target for cancer immunotherapy and infection control. NK cells display a diverse array of phenotypes and function. Determining how NK cells develop and are regulated is critical for understanding their role in both innate and adaptive immunity. In this review we discuss current research approaches into NK cell adaptive immunity and how these cells are being harnessed for improving …

Acute Disseminated Encephalomyelitis, Ashan Hatharasinghe, Hossein Akhondi, Don Pepito

HCA Healthcare Journal of Medicine

Introduction: Acute Disseminated Encephalomyelitis (ADEM) is a rare autoimmune demyelinating disorder of the central nervous system. Clinical manifestations include encephalopathy, motor deficits, ataxia, and meningeal signs. In most cases, ADEM is preceded by either vaccination or viral illness. Here, we present a case with neither of the two predisposing elements.

Discussion: A 28-year-old Hispanic female presenting with substance use and suicidal ideation was placed on an involuntary psychiatric hold, started on olanzapine and scheduled for a psychiatric facility transfer. The following day, she was noted to have neurological deficits when ambulating. Computed tomography of the brain showed a right frontal …