Immunology and Infectious Disease Commons^™

Passive Immunization Against Invasive Salmonella Enterica, Angelene Richards

Legacy Theses & Dissertations (2009 - 2024)

The Gram-negative bacterium, Salmonella enterica is a prominent etiologic agent of both diarrheal disease and enteric fever that encompasses over 2500 serovars, including S. Typhimurium (STm) and S. Typhi (STy). S. enterica is transmitted through contaminated food and water and, following ingestion, invades the gastrointestinal (GI) mucosa. The bacterium uses flagellar-based motility to target microfold (M) cells overlying gut-associated lymphoid tissues known as Peyer’s patches in the small intestine. Entry into Peyer’s patch tissues is a pivotal step in the infection process, as the bacterium can then disseminate systemically in the host. Given the rise in antibiotic resistance amongst S. …

Intrabodies Reveal Critical Steps Involved In Ricin's Interactions With The Ribosome, Timothy Francis Czajka

Legacy Theses & Dissertations (2009 - 2024)

Ricin is a highly lethal protein toxin derived from the seeds of the castor plant, Ricinus communis. It is a Type II ribosome inactivating protein (RIP), meaning it is a heterodimer with one subunit, ricin toxin B (RTB), that mediates cell surface attachment and intracellular trafficking and a second subunit, ricin toxin A (RTA), that irreversibly shuts down protein synthesis in the cytosol. During trafficking, RTA and RTB necessarily separate in the endoplasmic reticulum, wherein RTA unfolds and translocates into the cytosol where it refolds into an enzymatically active conformation. RTA is remarkably fast acting and efficient, with few molecules …

Female And Male-Controlled Livestock Holdings Impact Pastoralist Food Security And Women’S Dietary Diversity, Henriette Gitungwa, Christopher Gustafson, E.Y. Jimenez, E. Wesley F. Peterson, M. Mwanzalila, Asha Makweta, E. Komba, R.R. Kazwala, J.A.K. Mazet, Elizabeth Vanwormer

School of Veterinary and Biomedical Sciences: Faculty Publications

Background: Food insecurity is a global problem that requires a One Health approach. As many households in low- and middle-income nations rely on crops and livestock that they produce to meet their household’s needs, food security and nutrition are closely linked to the health of animals and the environment. Resources controlled by women are more often allocated to uses that benefit the entire household, such as food, health, and educating children, than men’s resources. However, studies of gender control of resources among pastoralist societies are scant. We examined the effect of female and male control of livestock resources on food …

Sars-Cov-2: An Investigation On Mutagenicity And Its Effects On Infectivity And Mortality, Tyler Elliott Silverwood

Honors Theses and Capstones

SARS-CoV-2, the etiological agent of the COVID-19 pandemic, has rapidly become a worldwide public health concern. Classified as a betacoronavirus, it is the third human coronavirus (HCoV) to emerge in the 21st century that causes severe disease, alongside SARS-CoV and MERS-CoV. The genome consists of open reading frames encoding accessory proteins and four structural proteins, including the spike protein which is a key determinant of host cell tropism. Mutations within the genome, particularly the spike gene, have been linked in-vitro to increased binding affinity to the human receptor angiotensin-converting enzyme 2 (hACE2), increased fitness in human hosts, and immune evasion. …

Impact Of Coronavirus Disease 2019 (Covid-19) Outbreak Quarantine, Isolation, And Lockdown Policies On Mental Health And Suicide, Balasankar Ganesan, Adel Al-Jumaily, Kenneth N. K. Fong, Palak Prasad, Surendra Kumar Meena, Raymond Kai-Yu Tong

Research outputs 2014 to 2021

The novel coronavirus disease (COVID-19) pandemic has made a huge impact on people's physical and mental health, and it remains a cause of death for many all over the world. To prevent the spread of coronavirus infection, different types of public health measures (social isolation, quarantine, lockdowns, and curfews) have been imposed by governments. However, mental health experts warn that the prolonged lockdown, quarantine, or isolation will create a “second pandemic” with severe mental health issues and suicides. The quarantined or isolated people may suffer from various issues such as physical inactivity, mental health, economic and social problems. As with …

Morphological Changes In Dorsal Root Ganglia Macrophages Associated With Neuropathic Pain Mechanisms Suggest A Novel Target For Chronic Pain Therapy, Emily Kussick

CMC Senior Theses

The present study examined morphological changes in the dorsal root ganglia (DRG) following an innate immune stimulus. The importance of the DRG has increasingly become recognized in pain processing as more than just the home of primary afferent cell bodies. All sensory information passes through the DRG via the primary afferents, and on to the spinal cord. The primary afferents synapse with second-order neurons in the spinal cord that ascend towards the brain, where they transmit the pain signal to the limbic forebrain and/or the somatosensory cortex for processing. The DRG is an interesting niche to study at as it …

Tick Ecdysteroid Hormone, Global Microbiota/Rickettsia Signaling In The Ovary Versus Carcass During Vitellogenesis In Part-Fed (Virgin) American Dog Ticks, Dermacentor Variabilis, Loganathan Ponnusamy, Haley Sutton, Robert D. Mitchell Iii, Daniel E. Sonenshine, Charles S. Apperson, Richard Michael Roe

Biological Sciences Faculty Publications

The transovarial transmission of tick-borne bacterial pathogens is an important mechanism for their maintenance in natural populations and transmission, causing disease in humans and animals. The mechanism for this transmission and the possible role of tick hormones facilitating this process have never been studied. Injections of physiological levels of the tick hormone, 20-hydroxyecdysone (20E), into part-fed (virgin) adult females of the American dog tick, Dermacentor variabilis, attached to the host caused a reduction in density of Rickettsia montanensis in the carcass and an increase in the ovaries compared to buffer-injected controls. This injection initiates yolk protein synthesis and uptake …

Il-10 And Tgf-Beta Increase Connexin-43 Expression And Membrane Potential Of Hl-1 Cardiomyocytes Coupled With Raw 264.7 Macrophages, Cora B. Cox

Browse all Theses and Dissertations

Cardiomyocytes and macrophages have been found to interact via connexin-43 hemichannels. The role of connexin-43, however, is not fully understood. This study shows that these interactions aid in increasing the membrane potential of cardiomyocytes allowing contraction of the cells. HL-1 cardiomyocytes and RAW 264.7 macrophages in coculture increased expression of connexin-43 compared to cardiomyocytes alone. Co-cultures also increased the fluorescence of Di-8-ANEPPS potentiometric dye indicating an increase in cardiomyocyte membrane potential. Treatment with IL-10 and TGF-beta further increased connexin-43 expression and membrane potential. Treatment with SOCS3 inhibited the effects of TGF-beta and IL-10 while having no effect on its own. …

Trends And Opportunities In Tick-Borne Disease Geography, Catherine A. Lippi, Sadie J. Ryan, Alexis L. White, Holly D. Gaff, Colin J. Carlson

Biological Sciences Faculty Publications

Tick-borne diseases are a growing problem in many parts of the world, and their surveillance and control touch on challenging issues in medical entomology, agricultural health, veterinary medicine, and biosecurity. Spatial approaches can be used to synthesize the data generated by integrative One Health surveillance systems, and help stakeholders, managers, and medical geographers understand the current and future distribution of risk. Here, we performed a systematic review of over 8,000 studies and identified a total of 303 scientific publications that map tick-borne diseases using data on vectors, pathogens, and hosts (including wildlife, livestock, and human cases). We find that the …

Antibodies Against Egf-Like Domains In Ixodes Scapularis Bm86 Orthologs Impact Tick Feeding And Survival Of Borrelia Burgdorferi, Juraj Koči, Sandhya Bista, Payal Chirania, Xiuli Yang, Chrysoula Kitsou, Vipin Singh Rana, Ozlem Buyuktanir Yas, Daniel E. Sonenshine, Utpal Pal

Biological Sciences Faculty Publications

Ixodes scapularis ticks transmit multiple pathogens, including Borrelia burgdorferi sensu stricto, and encode many proteins harboring epidermal growth factor (EGF)-like domains. We show that I. scapularis produces multiple orthologs for Bm86, a widely studied tick gut protein considered as a target of an anti-tick vaccine, herein termed as Is86. We show that Is86 antigens feature at least three identifiable regions harboring EGF-like domains (termed as EGF-1, EGF-2, and EGF-3) and are differentially upregulated during B. burgdorferi infection. Although the RNA interference-mediated knockdown of Is86 genes did not show any influences on tick engorgement or B. burgdorferi sensu stricto persistence, the …

Biology And Molecular Biology Of Ixodes Scapularis, Daniel E. Sonenshine, Ladislav Šimo, Justin D. Radolf (Ed.), D. Scott Samuels (Ed.)

Biological Sciences Faculty Publications

This chapter describes the biology of the tick Ixodes scapularis in relation to its role as the vector of the Lyme disease agent, Borrelia burgdorferi. Following a review of the internal anatomy of the tick, we review basic molecular processes that contribute to an understanding of the dynamics of the tick's specialized parasitic processes, including attachment behavior, salivation; silencing of host anti-inflammatory responses to enable blood ingestion at the dermal feeding site; hemoglobin digestion and reproduction. The chapter is divided into three parts: 1) systematic and anatomical characteristics of ticks; 2) host finding, attachment, salivary disruption of host defenses, blood …

Double Anus In An Ixodes Scapularis Nymph, A Medically Important Tick Vector, Vikas Taank, Frank A. Lattanzio, Hameeda Sultana, Girish Neelakanta

Biological Sciences Faculty Publications

Background: Ixodes scapularis ticks are medically important arthropod vectors that transmit several pathogens to humans. The observations of morphological abnormalities, including nanism, missing leg, extra leg, and gynandromorphism, have been reported in these ticks. In this study, we report the presence of two anuses in a laboratory-reared I. scapularis nymph.

Results: Larval ticks were allowed to feed on mice and to molt to nymphs. Two anuses were observed in one of the freshly molted nymphs. Stereo and scanning electron microscopy confirmed the presence of two anuses in one nymph within a single anal groove.

Conclusions: This report confirms the rare …

Sequence-Independent Assay For Hiv Viral Load Quantitation, Omar El Merhebi

Honors Undergraduate Theses

Although nucleic acid tests (NATs) for human immunodeficiency virus (HIV) exhibit many advantages, such as early detection and viral load quantification, over immunological assays, their widespread use is limited by their demand for high-level infrastructure, sophisticated equipment, and advanced staff competence. Furthermore, when quantifying viral loads of patients, it has been reported that these assays can underestimate viral quantities by 22- to 100-fold due to primer-template mismatches in more divergent HIV subtypes. Therefore, we have developed a cost-effective and sequence-independent assay for the detection and quantification of HIV utilizing a modified nucleic acid sequence-based amplification (NASBA) protocol coupled to an …

Human Regulatory T Cells Control Inflammation From Effector T Cells In Prediabetes, Rui Liu

Theses and Dissertations--Pharmacy

Type 2 diabetes (T2D) is a chronic low-grade inflammatory disease. A T cell cytokine profile (Th17) from PBMCs can distinguish obese T2D from obese non-diabetes subjects. Individual T cell subsets interact with each other and the diverse subsets jointly determine overall inflammation. Cellular metabolism drives cytokine production of CD4⁺ T cells, and therefore contributes to inflammation in T2D. However, specific changes in metabolism and function of CD4⁺ T cells during the progression from lean healthy to obese and diabetic stages in people have not been clarified.

We hypothesize that human regulatory T cells (Treg) impact metabolism of effector …

Muscle Mass And Immune Function In The Senior Horse, Alisa Christina Herbst

Theses and Dissertations--Veterinary Science

Senior horses (≥ 15 years) represent up to one-third of the global equine population, and the proportion of old horses (≥ 20 years) in the U.S. has been steadily increasing. Aging is associated with a loss of skeletal muscle mass in horses, and while age-related muscle loss is comparingly well characterized in humans, little is currently known concerning underlying mechanisms, adverse outcomes, or the prevalence of low muscle mass in senior horses. One factor proposed to play a role in the development of age-related muscle atrophy in humans is inflamm-aging, a low-grade inflammation that affects elderly people and that has …

The Intellectual Property Of Covid-19, Ana Santos Rutschman

All Faculty Scholarship

The response to COVID-19 is indissolubly tied to intellectual property. In an increasingly globalized world in which infectious disease pathogens travel faster and wider than before, the development of vaccines, treatments and other forms of medical technology has become an integral part of public health preparedness and response frameworks. The development of these technologies, and to a certain extent the allocation and distribution of resulting outputs, is informed by intellectual property regimes. These regimes influence the commitment of R&D resources, shape scientific collaborations and, in some cases, may condition the widespread availability of emerging technologies. As seen throughout this chapter, …

Covid-19 Employee Health Checks, Remote Work, And Disability Law, Elizabeth Pendo

All Faculty Scholarship

The Americans with Disabilities Act (ADA) prohibits discrimination against people with disabilities, about 61 million individuals in the U.S. The law’s protections in the workplace are especially important during COVID-19, which has worsened pre-existing disparities experienced by people with disabilities. The ADA also applies to new strategies to reduce the risk of COVID-19 infection in the workplace. This Chapter will focus on two strategies that impact individuals with and without disabilities – employee health screening, testing and vaccination policies, and new or expanded remote work programs.

Myelin, Cpla2, And Azithromycin: Modulation Of Macrophage Activation In Spinal Cord Injury Inflammation, Timothy J. Kopper

Theses and Dissertations--Physiology

Spinal cord injury (SCI) produces a chronic inflammatory state primarily mediated by macrophages consisting of resident microglia and infiltrating monocytes. These chronically activated SCI macrophages adopt a pro-inflammatory, pathological state that continues to cause additional damage after the initial injury and inhibits recovery. While the roles of macrophages in SCI pathophysiology are well documented, the factors contributing to this maladaptive response are poorly understood. Here, we identify the detrimental effects of myelin debris on macrophage physiology and demonstrate a novel, activation state-dependent role for cytosolic phospholipase-A2 (cPLA₂) in myelin- mediated potentiation of pro-inflammatory macrophage activation. Macrophage- mediated inflammatory …

Spatial And Temporal Variation In Aedes Albopictus Prevalence Across Arkansas, Alyssa N. Jones, Eric C. Lovely, Douglas G. Barron

Journal of the Arkansas Academy of Science

Aedes albopictus is a well-known vector species of mosquito that is responsible for the transmission of many arboviruses such as Zika, chikungunya, and dengue. The objective of this study was to quantify spatial and temporal variation of Ae. albopictus prevalence in Arkansas. We used egg abundance as a proxy for mosquito prevalence. Across 2 years, we worked with the Arkansas Department of Health to collect mosquito eggs using oviposition traps. Eggs were desiccated, counted, and later rehydrated in rearing chambers and raised through adulthood for species determination (>99% Ae. albopictus). We determined mean egg abundance by month, year, …

Development Of Environmental Metabarcoding Analysis For Use In Ecological Studies Of Aquatic Fungal And Oomycete Communities Using Nanopore Sequencing, Douglas Bennett

All Master's Theses

One of several factors contributing to amphibian decline are organisms called water molds (oomycetes), which parasitize and kill amphibian and fish eggs, larvae, and occasionally adults. Amphibian decline is one of the most difficult issues facing ecologists and conservationists to date; half of amphibian species are in severe decline and one third of amphibian species are facing extinction, threatening the stability of ecosystems globally. Multiple oomycete species are known to cause the disease saprolegniasis and contribute to amphibian decline; however, the full range of species involved is not presently known. This study evaluated the Oxford Nanopore minION DNA sequencer (R9.2 …

The Effects Of Genetic Differences In An Innate Immune Receptor On Immune Responses To Haemonchus Contortus In Sheep, Denzel Deshawn Middleton

Graduate Theses, Dissertations, and Problem Reports (ETD)

Little is known about differences observed in early immunological signaling events that result in cellular infiltration and Th2 cytokine production that mediate parasite expulsion. Parasite resistant St. Croix (STC) sheep have been used as model for full host protective immunity as they present the ability to respond to larval stages of H. contortus. RNA sequencing analysis of peripheral blood mononuclear cells (PBMC) stimulated with H. contortus larval antigen (HcLA) revealed significant upregulation in NLRP3 and its pathway component TLR4. Predicted protein structural software identified distinct differences in NLRP3 protein structure in STC and parasite susceptible Suffolk (SUF) sheep. NLRP3 …

Pseudomonas Aeruginosa Vaccine Development Using Dual-Species Whole Cell And Subunit Vaccines, Catherine Bell Blackwood

Graduate Theses, Dissertations, and Problem Reports (ETD)

Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen which can cause severe, recurrent, and chronic infections. The pathogen is highly adaptable, and pneumonia caused by it is associated with high morbidity and mortality, especially in individuals with the genetic disorder cystic fibrosis. Antibiotic resistance amongst clinical isolates of P. aeruginosa is steadily increasing, and multi-drug resistant strains are prevalent. There is currently no vaccine available for commercial use against P. aeruginosa. For these reasons, we sought to understand the immunity to P. aeruginosa induced by whole cell vaccination and identify antigens for development of future subunit vaccines. In this dissertation, …

A Survey Of Anthelmintic Resistance In Angus Bulls Participating In Centralized Performance Tests In Appalachia, Roger Tyler Rohrbaugh

Graduate Theses, Dissertations, and Problem Reports (ETD)

Resistance to anthelmintics, more commonly referred to as “de-wormers,” has been on the rise in parasites that affect cattle. Parasite infection can have severe impacts on calf productivity resulting in reduced profitability. Therefore, we sought to better understand anthelmintic resistance in Appalachia by surveying Angus bulls entering performance tests in VA and WV. During a four-year period, over 1050 Angus bulls were tested at bull development facilities in Wardensville, WV, Culpeper, VA and Wytheville, VA. Fecal samples were collected at arrival and 14-21 days later for determination of fecal egg count (FEC) reduction. Upon arrival, all bulls received either fenbendazole …

Il-10 And Tgf-Beta Increase Connexin-43 Expression And Membrane Potential Of Hl-1 Cardiomyocytes Coupled With Raw 264.7 Macrophages, Cora B. Cox

Browse all Theses and Dissertations

Cardiomyocytes and macrophages have been found to interact via connexin-43 hemichannels. The role of connexin-43, however, is not fully understood. This study shows that these interactions aid in increasing the membrane potential of cardiomyocytes allowing contraction of the cells. HL-1 cardiomyocytes and RAW 264.7 macrophages in coculture increased expression of connexin-43 compared to cardiomyocytes alone. Co-cultures also increased the fluorescence of Di-8-ANEPPS potentiometric dye indicating an increase in cardiomyocyte membrane potential. Treatment with IL-10 and TGF-beta further increased connexin-43 expression and membrane potential. Treatment with SOCS3 inhibited the effects of TGF-beta and IL-10 while having no effect on its own. …

Investigating Streptococcus Pneumoniae And Adenovirus Co-Infections Of Lung Epithelial Cells, Mark Nicholas Calabro

Browse all Theses and Dissertations

Co-infection is common among viruses and bacteria in the human respiratory system. Adenovirus (AdV) and Streptococcus pneumoniae are clinically relevant respiratory pathogens that cause morbidity and mortality in a variety of patient populations with the highest morbidity occurring among immunocompromised individuals, but also prevalent in infants and the elderly. Acute respiratory distress syndrome may become severe in healthy individuals when co-infection with S. pneumoniae and AdV occurs due to synergistic effects of the pathogens on the host. I hypothesized that S. pneumoniae infection decreases AdV transduction of airway epithelia. To test this hypothesis, we utilized the polarized immortalized airway epithelial …

Molecular Determinants Of Fetal Tolerance And The Transition To Adult Immunity, Yi Wei Lim

Dissertations

The perinatal immune system is highly tolerogenic and is phenotypically and functionally distinct from the adult immune system. This tolerogenic nature is a double-edged sword for newborns. While it is beneficial to prevent excessive inflammation against the vast array of foreign antigens encountered after birth, it also causes a lack of immune responses to life-threatening infections. My dissertation research aims to investigate the mechanisms by which perinatal T cells contribute to immune tolerance in infants. A deeper understanding of the nature of the perinatal immune system will provide pivotal knowledge to develop safe and effective strategies to protect infants from …

Regulation Of Osseous Healing By Macrophage-Derived Wnt Ligands, Jefferson Overlin Abaricia

Theses and Dissertations

Osseous healing is regulated by various classes of cells and signaling mechanisms. Of these, Wnt signaling has long been known to be critically important in directing the differentiation of mesenchymal stem cells (MSCs) into osteoblasts during bone healing. However, the source of these Wnt ligands is not known. Recently, a body of literature has arisen finding both beneficial and detrimental effects of macrophage-derived Wnt ligands on the regeneration of other tissues (liver, kidney, heart, and intestine), often by regulating inflammatory activation and stem cell behavior. As macrophages have been well-characterized as orchestrators of healing, their use of Wnt signaling to …

Investigating Streptococcus Pneumoniae And Adenovirus Co-Infections Of Lung Epithelial Cells, Mark Nicholas Calabro

Browse all Theses and Dissertations

Co-infection is common among viruses and bacteria in the human respiratory system. Adenovirus (AdV) and Streptococcus pneumoniae are clinically relevant respiratory pathogens that cause morbidity and mortality in a variety of patient populations with the highest morbidity occurring among immunocompromised individuals, but also prevalent in infants and the elderly. Acute respiratory distress syndrome may become severe in healthy individuals when co-infection with S. pneumoniae and AdV occurs due to synergistic effects of the pathogens on the host. I hypothesized that S. pneumoniae infection decreases AdV transduction of airway epithelia. To test this hypothesis, we utilized the polarized immortalized airway epithelial …

Global Distribution, Host Range And Prevalence Of Trypanosoma Vivax: A Systematic Review And Meta-Analysis, Eyerusalem Fetene, Samson Leta, Fikru Regassa, Philippe Büscher

Harold W. Manter Laboratory of Parasitology: Library Materials

Background

Trypanosomosis caused by Trypanosoma vivax is one of the diseases threatening the health and productivity of livestock in Africa and Latin America. Trypanosoma vivax is mainly transmitted by tsetse fies; however, the parasite has also acquired the ability to be transmitted mechanically by hematophagous dipterans. Understanding its distribution, host range and prevalence is a key step in local and global efforts to control the disease.

Methods

The study was conducted according to the methodological recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. A systematic literature search was conducted on three search engines, namely PubMed, …

Special Issue: Shiga Toxin-Producing Escherichia Coli, Rodney A. Moxley

School of Veterinary and Biomedical Sciences: Faculty Publications

Globally, Shiga toxin-producing Escherichia coli (STEC) is an important cause of diarrheal disease, most notably hemorrhagic colitis, and post-diarrheal sequela, such as hemolytic-uremic syndrome (HUS) [1]. Cattle are a major reservoir of STEC, with approx- imately half of the cases in humans attributable to foodborne exposure [2]. Prevention of human illness has mainly been through food safety measures [2]. Despite extensive research, no other generally accepted and effective preventive measures or therapies for STEC infections in human patients are available [3]. Many questions remain about STEC virulence factors, pathogenesis, detection, and other aspects that necessitate a continua- tion of basic …