Immunology and Infectious Disease Commons^™

Development Of Cellular Assays To Monitor Enzymatic And Biological Activity Of Cd73: A Key Modulator Of Anti-Tumor Immune Response, Alexandra Fanuka

Graduate School of Biomedical Sciences Theses and Dissertations

Ecto-5’-nucleotidase, known as CD73, is an extracellular enzyme that converts adenosine monophosphate (AMP) to adenosine and has recently been identified as a potential drug target for cancer immunotherapy. Its immunosuppressive effects, mediated by the activity of adenosine, are associated with higher rates of tumor invasion and metastasis, as well as poorer prognoses overall in many cancer types. CD73 is often co-expressed with ectonucleoside triphosphate diphosphohydrolase-1 (CD39), which catalyzes the conversion of adenosine triphosphate (ATP) to adenosine diphosphate (ADP), and ADP to AMP on the surface of tumor cells. Dual expression further propagates immunosuppressive effects of adenosine in the tumor microenvironment. …

Cytokine Expression, Cytoskeleton Organization, And Viability Of Sim-A9 Microglia Exposed To Staphylococcus Aureus-Derived Lipoteichoic Acid And Peptidoglycan, Erin Roberts

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In these experiments, SIM-A9 microglia were exposed to Staphylococcus aureus cell wall components lipoteichoic acid (LTA) and peptidoglycan (PGN) at a concentration of 5 ug/mL for six, twelve, eighteen, and twenty-four hours and the cytokine expression, cytoskeleton organization, and cell viability of the cells were observed. Following LTA and PGN exposure, TNF-a; secretion increased at each time interval and was highest observed at 24 hours. No significant IL-10 secretion was detected. Over the 24 hour period, cell viability and cytotoxicity of LTA and PGN treatment groups were not significantly different from the control, indicating the observed inflammatory cytokine response was …

Genomic Vs. Non-Genomic Role Of The Ahr In Human Immunoglobulin Expression, Nasser Alhamdan

Browse all Theses and Dissertations

The immunoglobulin heavy chain gene (Igh) in various animal models is regulated by numerous regulatory elements including the 3’Igh regulatory region (3’IghRR). Several transcription factors are involved in modulating the 3’IghRR including the aryl hydrocarbon receptor (AhR). The AhR is a ligand-activated transcription factor that mediates the transcription of genes involved in the metabolism of environmental toxicants such as TCDD. TCDD binds AhR and regulates immunoglobulin (Ig) expression in B cells. This modulation appears to be directly mediated by binding of the AhR to dioxin response elements (DRE) within the 3’IghRR. In human B cells, IgG secretion inhibited by TCDD …

Sleep Disturbance And The Immunological Acute Phase Response In Hospitalized Post-Operative Adults., Jean Dorothy Humphries

Wayne State University Dissertations

Abstract

Sleep Disturbance and the Immunological Acute Phase Response

in Postoperative Hospitalized Adults

Abstract

The purpose of this study was to examine the subjective and objective (actigraphy) sleep patterns, the immunological acute phase response of IL1-β and TNF-α, and the physiological stress response of cortisol and systolic blood pressure in post-operative abdominal surgical patients. Nineteen subjects, 10 men and 9 women, mean age 45.63 years (SD = 11.44) were enrolled between April 2015 and March 2016. All subjects were elective major invasive abdominal surgery patients. Laparoscopic surgery occurred in 10 patients and incisional surgery occurred in 9 patients. This descriptive …

Effects Of Socs1 And Socs3 Peptide Mimetics On Macrophage Phagocytosis Of Malignant Cells, Colt Dylan Capan

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Macrophages play a key role in both the innate and adaptive immune system responses to foreign materials. Suppressors of cytokine signaling (SOCS) proteins are known as regulators of the immune response through various JAK/STAT pathways. This study examined the roles of SOCS1 and SOCS3 peptide mimetics on the phagocytosis of fluorescently labeled malignant target cell by RAW264.7 murine macrophages. The malignant cells used were Neuro-2a cells, a murine neuroblastoma cell line. A prominent “eat me” signal found in neuroblastoma cells is calreticulin (CRT), which permits macrophages to recognize and then phagocytize the malignant cells. When M1 (pro-inflammatory) polarized macrophages were …

Nasopharyngeal Microbiome Diversity Changes Over Time In Children With Asthma, Marcos Pérez-Losada, Lamia Alamri, Keith Crandall, Robert J. Freishtat

Pediatrics Faculty Publications

Background

The nasopharynx is a reservoir for pathogens associated with respiratory illnesses such as asthma. Next-generation sequencing (NGS) has been used to characterize the nasopharyngeal microbiome of infants and adults during health and disease; less is known, however, about the composition and temporal dynamics (i.e., longitudinal variation) of microbiotas from children and adolescents. Here we use NGS technology to characterize the nasopharyngeal microbiomes of asthmatic children and adolescents (6 to 18 years) and determine their stability over time.

Methods

Two nasopharyngeal washes collected 5.5 to 6.5 months apart were taken from 40 children and adolescents with asthma living in the …

Immune Evasion By Division Of Labor: The Trophic Life Cycle Stage Of Pneumocystis Murina Suppresses Innate Immunity To This Opportunistic, Fungal Pathogen, Heather M. Evans

Theses and Dissertations--Microbiology, Immunology, and Molecular Genetics

Pneumocystis species are opportunistic fungal pathogens that cause severe pneumonia in immunocompromised hosts, including AIDS patients. Pneumocystis species have a biphasic life cycle consisting of single-nucleated trophic forms and ascus-like cysts. Both stages live within the host, and, thus, must contend with threats from the host immune system. The cyst cell wall β-glucans have been shown to stimulate immune responses in lung epithelial cells, dendritic cells and alveolar macrophages. Little is known about how the trophic life forms, which do not have a fungal cell wall, interact with immune cells. In this study, the immune response to the life cycle …

The Outcome Of Elisa For Antiphosphatidylethanolamine Antibodies Is Dependent On The Composition Of Phosphatidylethanolamine, Songwang Hou, Paul E. Harper, Nathalie Bardin, Ming Zhao

University Faculty Publications and Creative Works

Objective The presence of circulating autoantibodies against phosphatidylethanolamine (PE) has been shown to be positively associated with symptoms of antiphospholipid syndromes (APS). However, the current ELISA-based tests for antiphosphatidylethanolamine (aPE) antibodies remain inconsistent and controversial. The term PE refers to a collection of phospholipids that have phosphorylethanolamine head group as a common structural feature, but can vary in fatty acids with diverse physicochemical properties. The present study was to investigate, using synthetic positionally symmetrical PE species as a model system, the impact of PE structural variations on aPE ELISA. Methods Single and combinations of synthetic PE species, including 16:0 (fatty …

Genomic Vs. Non-Genomic Role Of The Ahr In Human Immunoglobulin Expression, Nasser Alhamdan

Browse all Theses and Dissertations

The immunoglobulin heavy chain gene (Igh) in various animal models is regulated by numerous regulatory elements including the 3'Igh regulatory region (3'IghRR). Several transcription factors are involved in modulating the 3'R including the aryl hydrocarbon receptor (AhR). The AhR is a ligand-activated transcription factor that mediates the transcription of genes involved in the metabolism of environmental toxicants such as TCDD. TCDD binds AhR and regulates immunoglobulin (Ig) expression in B cells. This modulation appears to be directly mediated by binding of the AhR to dioxin response elements (DRE) within the 3'IghRR. In human B cells, IgG secretion inhibited by TCDD …

The Fleas (Arthropoda: Insecta: Siphonaptera) Of Arkansas, Chris T. Mcallister, Lance A. Durden, Henry W. Robison, Matthew B. Connior

Journal of the Arkansas Academy of Science

Fleas (Insecta: Siphonaptera) are important ectoparasites of cats, dogs, other mammals (including humans), and birds, and are an important component of the biota of North America. In addition, they can be nuisance biters and serve as vectors or intermediate hosts of several flea-borne disease agents and parasites that negatively affect mammals and birds. In Arkansas, there have been no recent comprehensive summaries of fleas in the last 45+ years. Here, we provide a summary of the 29 species of fleas within 7 families that have been recorded from the state, update their taxonomy, and note their medical and veterinary importance.

Association Of Gut Luminal Metabolites And Allergic Responses, Ghaith Mohammed Fallata

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Allergy is a global health problem, affecting more than 40% of the world population. Allergy is often associated with a dysregulation of the immune system that becomes overactive against allergens. Several genes are known to be important for the proper homeostasis of the immune system in the epithelial tissues, and the loss of function of genes such as IKKß or SOX9 impacts the interaction between external stimuli and the host. Many of the allergic responses are triggered through the regulatory cascade governed by transcriptional factor NF-κB. Regulation of NF-κB activity is complex, involves several alternative routes, and is also influenced …

Detoxification Of Mitochondrial Oxidants And Apoptotic Signaling Are Facilitated By Thioredoxin-2 And Peroxiredoxin-3 During Hyperoxic Injury, Benjamin J. Forred, Darwin R. Daugaard, Brianna K. Titus, Ryan R. Wood, Miranda J. Floen, Michelle L. Booze, Peter F. Vitiello

School of Veterinary and Biomedical Sciences: Faculty Publications

Mitochondria play a fundamental role in the regulation of cell death during accumulation of oxidants. High concentrations of atmospheric oxygen (hyperoxia), used clinically to treat tissue hypoxia in premature newborns, is known to elicit oxidative stress and mitochondrial injury to pulmonary epithelial cells. A consequence of oxidative stress in mitochondria is the accumulation of peroxides which are detoxified by the dedicated mitochondrial thioredoxin system. This system is comprised of the oxidoreductase activities of peroxiredoxin-3 (Prx3), thioredoxin-2 (Trx2), and thioredoxin reductase-2 (TrxR2). The goal of this study was to understand the role of the mitochondrial thioredoxin system and mitochondrial injuries during …

Maternal Inflammation At Mid-Gestation In Pregnant Rats Impairs Fetal Muscle Growth And Development At Term, C. N. Cadaret, K. A. Beede, E. M. Merrick, T. L. Barnes, J. D. Loy, D. T. Yates

School of Veterinary and Biomedical Sciences: Faculty Publications

Intrauterine growth restriction (IUGR) is a leading cause of perinatal morbidity and mortality. Low birth weight resulting from preterm birth and/or IUGR is an underlying factor in 60–80% of perinatal death worldwide, and is particularly common in developing countries (UNICEF, 2008). Furthermore, studies have linked IUGR and the associated fetal malnutrition to increased incidence of metabolic syndrome in adult life (Barker et al., 1993; Godfrey and Barker, 2000). The “thrifty phenotype hypothesis” developed by David Barker (Hales et al., 1991) states that IUGR-associated fetal malnutrition forces the fetus to spare nutrients by altering tissue-specific metabolism in order to survive. In …

A Parapoxviral Virion Protein Targets The Retinoblastoma Protein To Inhibit Nf-Κb Signaling, Ponnuraj Nagendraprabhu, Sushil Khatiwada, Sabal Chaulagain, Gustavo A. Delhon, Daniel L. Rock

School of Veterinary and Biomedical Sciences: Faculty Publications

Poxviruses have evolved multiple strategies to subvert signaling by Nuclear Factor κB (NF-κB), a crucial regulator of host innate immune responses. Here, we describe an orf virus (ORFV) virion-associated protein, ORFV119, which inhibits NF-κB signaling very early in infection (≤30 min post infection). ORFV119 NF-κB inhibitory activity was found unimpaired upon translation inhibition, suggesting that virion ORFV119 alone is responsible for early interference in signaling. A C-terminal LxCxE motif in ORFV119 enabled the protein to interact with the retinoblastoma protein (pRb) a multifunctional protein best known for its tumor suppressor activity. Notably, experiments using a recombinant virus containing an ORFV119 …

Contributions Of Myd88-Dependent Receptors And Cd11c-Positive Cells To Corneal Epithelial Barrier Function Against Pseudomonas Aeruginosa, Matteo M. E. Metruccio, Connie Tam, David J. Evans, Anna L. Xie, Michael E. Stern, Suzanne M. J. Fleiszig

Faculty Publications & Research of the TUC College of Pharmacy

Previously we reported that corneal epithelial barrier function against Pseudomonas aeruginosa was MyD88-dependent. Here, we explored contributions of MyD88-dependent receptors using vital mouse eyes and confocal imaging. Uninjured IL-1R (−/−) or TLR4 (−/−) corneas, but not TLR2 (−/−), TLR5 (−/−), TLR7 (−/−), or TLR9 (−/−), were more susceptible to P. aeruginosa adhesion than wild-type (3.8-fold, 3.6-fold respectively). Bacteria adherent to the corneas of IL-1R (−/−) or TLR5 (−/−) mice penetrated beyond the epithelial surface only if the cornea was superficially-injured. Bone marrow chimeras showed that bone marrow-derived cells contributed to IL-1R-dependent barrier function. In vivo, but not ex vivo …

Using Rainbow Trout Cell Lines As A Model For Understanding The Innate Anti-Fv3 Immune Response, Graeme Robert Jones Lisser

Theses and Dissertations (Comprehensive)

Ranavirus infections are on the rise and have been implicated in numerous species die-offs across the globe. Frog virus 3 (FV3) is the type-species of the genus, yet the immune mechanisms governing susceptibility remain poorly understood. Arguably the most important immune response to infection is the type I interferon (IFN) response. Type I IFNs trigger an “antiviral state” in host cells via the production of numerous interferon-stimulated genes (ISGs) that act to inhibit virus replication in various way, including the induction of apoptosis. Apoptosis is an important antiviral defense mechanism to limit virus replication within infected cells. This study employed …

The Novel Characterization Of Extracellular Vesicles Containing Proteins Which Have Been Implicated In The Pathogenesis Of Hiv Associated Neurocognitive Disorders, Grace Ispas

Master's Theses

Although Anti-Retroviral Therapy (ART) is practiced, HIV-1 positive individuals still experience HIV-Associated Neurocognitive Disorders (HAND), collectively described as the presentation of neurocognitive, behavioral and motor dysfunctions that decrease the quality of life, while increasing the mortality in ART suppressed HIV-1 positive patients.

Current literature suggests that extracellular vesicles are involved in the pathogenesis of HAND as they are believed to be transferring HIV-1 proteins to nearby neuronal cells. Although most studies assume homogeneity among populations, characterizing cellular proteins or RNA levels in bulk, we hypothesize that distinct populations of extracellular vesicles are released and that environmental conditions, including viral infections, …

Multifunctional Regulatory T Cells From Human Umbilical Cord Blood And The Role Of Tumor Necrosis Factor In Immune Homeostasis, Alexander Nelson

Master's Theses

Regulatory T cells (Tregs) are required to suppress inflammation and prevent autoimmunity. During fetal development Tregs are crucial to maintain tolerance between mother and child. After birth, neonates require tolerance to avoid harmful immune responses to foreign antigens in food and allow colonization with commensal microbes. We demonstrate a propensity for T cells in human umbilical cord blood to differentiate into Tregs in response to antigen receptor stimulation ex vivo. Cord blood-derived Tregs potently suppress T cell proliferation, but also produce pro-inflammatory cytokines known to activate innate immune responses. These results suggest that antigen exposure during early life results in …

Dexamethasone Treatment Effects On H3k27me3 Chromatin Organization Is Related To Nk Cell Immune Dysregulation, Michael Sarafeno Misale

Master's Theses

It is well-established that psychological stress reduces natural killer (NK) cell immune function. This reduction is mediated by stress-induced release of glucocorticoids (GC), which can suppress immune function. Associated with suppression of a particular immune function are GC induced histone-epigenetic marks. Histone-epigenetic marks are responsible for the organization and compartmentalization of genomes into transcriptionally active euchromatin domains that are localized to the interior of the nucleus. Transcriptionally silent heterochromatic domains are enriched with methylated epigenetic marks and are localized to the nuclear periphery. The purpose of this investigation was to assess the influence of GC on H3K27me3 chromatin organization by …

Secondary Data Analysis: A Non-Pharmacology Treatment For Individuals Living With Hiv/Aids, Joseph Jean, Carolee Dodge-Francis Ed.D

McNair Poster Presentations

At the end of 2015, 36.7 million people were living with HIV/AIDS world wide (WHO, 2017). Living with this disease puts individuals at increased risk for mental and physical health complications. Opportunistic infections and increased serious mental health conductions are common (NIH, 2016). Advances in antiretroviral therapies have been made to increase life expectancy but often times can adversely affect the individuals quality of life. Complementary and alternative medicine (CAM) is one way to help improve quality of life. One form of CAM, massage therapy may offer benefits to PLWHA in terms of ability to cope with stress.