Immunology and Infectious Disease Commons^™

Human-Bat Interactions In A Disease Emergence Hotspot: Implications For Human Health And Bat Conservation, Reilly Tempest Jackson

Graduate Theses and Dissertations

Bats are an ecologically important taxon that can host zoonotic pathogens. Globally, many bat species are synanthropic and live closely with humans, often roosting in man-made structures. The spatial overlap between humans and bats creates opportunities for human-bat contact, which can lead to human exposure to bat-borne pathogens and conflicts that cause bat mortality. Despite this risk, little is known about the drivers and characteristics of these human-bat interactions in buildings and work is needed to understand this aspect of the wildlife-urban interface. In Chapter I, I present a literature review that identifies the geographic and taxonomic trends in reported …

Optimization Of Clostridium Septicum Antigen Production And Evaluation Of Vaccine Administration Parameters For A Candidate Bacterin-Toxoid To Prevent Dermatitis In Commercial Turkeys, Aaron Forga

Graduate Theses and Dissertations

The objective of this thesis was to optimize the hemolytic activity of two isolates of Clostridium septicum to evaluate if hemolytic titer of C. septicum antigen at time of formalin inactivation corresponded to increased serum antibody titer to the C. septicum alpha-toxin of turkeys immunized with an experimental formalin inactivated bacterin-toxoid vaccine. Chapter 1 provides a brief overview of the thesis. Chapter 2 consists of a literature review focused on clostridial dermatitis, specifically C. septicum-associated dermatitis (cellulitis) that affects commercial turkeys. Chapter 3 outlines our attempts to optimize an experimental autogenous bacterin-toxoid vaccine as a potential strategy to mitigate clostridial …

The Effect Of Infection Risk On Female Blood Transcriptomics, Brenna M. G. Gormally, Patricia C. Lopes

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Defenses against pathogens can take on many forms. For instance, behavioral avoidance of diseased conspecifics is widely documented. Interactions with these infectious conspecifics can also, however, lead to physiological changes in uninfected animals, an effect that is much less well understood. These changes in behavior and physiology are particularly important to study in a reproductive context, where they can impact reproductive decisions and offspring quality. Here, we studied how an acute (3 h) exposure to an immune-challenged male affected female blood transcriptomics and behavior. We predicted that females paired with immune-challenged males would reduce eating and drinking behaviors (as avoidance …

Prenatal Choline Supplementation During Maternal Obesity Alters Offspring Response To Western Diets, Hunter W. Korsmo

Dissertations, Theses, and Capstone Projects

Maternal obesity has led to an increase in adverse offspring developmental outcomes and a greater risk for long-term metabolic diseases. Choline, a semi-essential nutrient, can be incorporated into phosphatidylcholine (PC) as well as sphingomyelin (SM) and donate its labile methyl group for the remethylation of homocysteine after choline is oxidized to betaine. Prenatal choline insufficiency has been related to maternal obesity and metabolic diseases, such as metabolic associated fatty liver disease (MAFLD). Choline may interact with maternal obesity to influence the programming offspring.

Chapter 1 presents an introduction of choline and the various clinical outcomes associated with choline supplementation during …

The Role Of The Hypoxia-Inducible Factor 2 In Pancreatic Cancer: Mechanisms Of Tumor Immunosuppression And Intestinal Radioprotection, Carolina Garcia Garcia

Dissertations & Theses (Open Access)

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with dismal prognosis. The only curative option for patients is surgery, but over 80% of patients are not surgical candidates. Unfortunately, PDAC is resistant to the three remaining options. PDAC is characterized by a profoundly hypoxic and immunosuppressive stroma, which contributes to its therapeutic recalcitrance. Alpha-smooth muscle actin+ (αSMA+) cancer-associated fibroblasts (CAFs) are the most abundant stromal component, as well as mediators of stromal deposition. The hypoxia-inducible factors (HIF1 and HIF2) coordinate responses to hypoxia, yet, despite their known association to poor patient outcomes, their functions within the PDAC tumor microenvironment (TME) …

Maternal Responses In The Face Of Infection Risk, Patricia C. Lopes, Brenna M. G. Gormally, Aubrey Emmi, Delilah Schuerman, Chathuni Liyanage, Ursula K. Beattie, L. Michael Romero

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

When animals are sick, their physiology and behavior change in ways that can impact their offspring. Research is emerging showing that infection risk alone can also modify the physiology and behavior of healthy animals. If physiological responses to environments with high infection risk take place during reproduction, it is possible that they lead to maternal effects. Understanding whether and how high infection risk triggers maternal effects is important to elucidate how the impacts of infectious agents extend beyond infected individuals and how, in this way, they are even stronger evolutionary forces than already considered. Here, to evaluate the effects of …

Female Presence Does Not Increase Testosterone But Still Ameliorates Sickness Behaviours In Male Japanese Quail, Brenna M. G. Gormally, Kaelyn Bridgette, Aubrey Emmi, Delilah Schuerman, Patricia C. Lopes

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Infections can dramatically modify animal behaviour. The extent of these changes depends on an animal's environment. It has been proposed that testosterone modulates the suppression of behavioural symptoms of sickness under certain reproductive contexts. To further understand the role played by testosterone in modulating sickness behaviours under reproductive contexts, we studied a species, the Japanese quail, in which female exposure rapidly decreases circulating testosterone in males. Males received either an immune challenge (lipopolysaccharide – LPS) or a control injection and their behaviours, mass change and testosterone levels were quantified in the presence or absence of a female. Both the presence …

The Role Of Calprotectin In T-Lymphocyte Driven Inflammation In A Mouse Model Of Psychological Trauma, Cassandra Moshfegh

Theses & Dissertations

Post-traumatic stress disorder (PTSD) is a debilitating psychological disorder that affects nearly 45 million Americans. This mental disorder is characterized by behavioral symptoms such as learned helplessness, hyperarousal, withdrawal, and flashbacks. The deleterious effects of PTSD are far-reaching and go beyond behavioral dysfunction, as these individuals are at a three-fold higher risk of comorbid inflammatory diseases. Autonomic, metabolic, and cardiovascular diseases plague these individuals later in their lifetime, however, the mechanistic link connecting psychological trauma to this systemic peripheral immunological dysfunction remains elusive. T-lymphocyte-induced inflammation plays a significant role in all these disease pathologies. Previous work from our laboratory demonstrated …

Comparison Of Percutaneous Vs Oral Infection Of Hamsters With The Hookworm Ancylostoma Ceylanicum: Parasite Development, Pathology And Primary Immune Response, Richard D. Bungiro, Lisa M. Harrison, Blaise Dondji, Michael Cappello

Biology Faculty Scholarship

Background

Hundreds of millions of people in poor countries continue to suffer from disease caused by bloodfeeding hookworms. While mice and rats are not reliably permissive hosts for any human hookworm species, adult Golden Syrian hamsters are fully permissive for the human and animal pathogen Ancylostoma ceylanicum. Similar to humans, hamsters may be infected with A. ceylanicum third-stage larvae orally or percutaneously. Oral infection typically leads to consistent worm yields in hamsters but may not accurately reflect the clinical and immunological manifestations of human infection resulting from skin penetration.

Methodology/Principal findings

In this study we compared host responses …

Investigation Of Histomoniasis Prevention In Poultry, Lesleigh Beer

Graduate Theses and Dissertations

Histomonas meleagridis is the etiological agent of histomoniasis, also commonly known as blackhead disease. This protozoal disease of poultry is detrimental to turkeys with flock mortalities often reaching 80-100%, although other gallinaceous birds are susceptible. Since the voluntary removal of nitarsone in 2015, the poultry industry is suffering with no approved prophylactics, therapeutics, or vaccines for this disease. The objectives of this dissertation were to evaluate multiple methods for prevention or control of histomoniasis, including dietary chemoprophylaxis and vaccination. Specifically, this research evaluated quinine as a chemoprophylactic candidate (Chapter 3) or live-attenuated H. meleagridis as vaccine candidates (Chapter 4) in …

Exogenous Surfactant As A Delivery Vehicle For Intrapulmonary Therapeutics, Brandon J. Baer

Electronic Thesis and Dissertation Repository

As an organ system, the lung has unique advantages and disadvantages for direct drug delivery. Its contact with the external environment allows for the airways to be easily accessible to intrapulmonary delivery. However, its complex structure, which divides into more narrow airways with each branch, can make direct delivery to the remote alveoli challenging. The objective of this thesis was to overcome this issue by using exogenous surfactant, a lipoprotein complex used to treat neonatal respiratory distress syndrome, as a carrier for pulmonary therapeutics. It was hypothesized that therapeutics administered with a surfactant vehicle would display enhanced delivery to the …

Combination Of Oncolytic Adenoviruses, T-Cell Activation, And Blockade Of Ido Metabolic Circuitry For The Treatment Of Glioma, Teresa Nguyen

Dissertations & Theses (Open Access)

Glioblastoma is the most common malignant primary brain tumor in adults; the current aggressive treatment results in a 5% five-year survival rate. More effective therapies should be developed. One promising alternative is oncolytic adenovirus, Delta-24-RGD, which elicits cancer cell lysis and immunogenic cell death. In fact, Delta-24-RGD produced complete responses in 20% of recurrent glioblastoma patients through immune mechanisms that activate anti-tumor cytotoxic properties of T-cells. This cytolytic effect can further be enhanced by adding immune agonists, namely OX40L, which engages the OX40 receptor to co-stimulate activated T cells for enhanced proliferation. Hence, we produced the next generation of Delta-24-RGD, …

21°C Is The Emerging Ideal Temperature For Kidney Preservation In The Presence Of Hydrogen Sulfide, Smriti Juriasingani

Electronic Thesis and Dissertation Repository

Kidney transplantation is the treatment of choice for patients with end-stage kidney disease. However, the shortage of transplantable kidneys has led to ever-increasing waiting lists. As a result, kidneys obtained via donation after cardiac death (DCD) are being used more frequently for transplantation. However, they exhibit poorer outcomes due to ischemia-reperfusion injury (IRI) and cold preservation methods, such as static cold storage (SCS). Supplementing cold preservation solutions with hydrogen sulfide donors, such as AP39, has been shown to improve renal IRI and graft outcomes, but the injury associated with cold preservation remains. This thesis evaluates the effect of subnormothermic kidney …

Host-Parasite Interactions Within Food Webs, Adam Zvanut Hasik

Graduate Theses and Dissertations

Parasitism is one of the most common life history strategies employed in nature, yet the effects of parasites are often thought to be minimal, and the vast majority of studies fail to consider parasites and their effects on host organisms. This is likely a problem, as the magnitude of parasite-mediated effects on their hosts can be quite large. Additionally, the effects of parasites are known to extend beyond the host to affect other species interactions. I used a series of approaches to gain a more integral understanding of host-parasite interactions by studying (1) the effects of parasites on biotic interactions …

Unraveling Host-Gut Microbiota Dialogue And Its Impact On Response To Immune Checkpoint Blockade, Alexandria Cogdill

Dissertations & Theses (Open Access)

Cancer is a disease with only one degree of separation, affecting one in two men and one in three women in their lifetimes; accounting for 1 of every 6 deaths. While cancer mortality rates continue to improve, incidence rates are expected to rise and shift through 2050 due to epidemiological and demographic transitions worldwide. As such, it is imperative to continue to investigate and improve our understanding of both disease etiology and hallmarks of response to treatment. Currently, conventional therapies include, but are not limited to, surgery, chemotherapy, and radiotherapy. However, within the past decade, major advances have been made …

Dirofilaria Immitis Prevalence In Canis Latrans In Kentucky, Melanie Ann Brandon

Murray State Theses and Dissertations

Dirofilaria immitis (canine heartworm) was found in forty-two (42) of the two hundred seventy-five (275) Canis latrans (coyote) necropsied in the state of Kentucky from November 27, 2019 through March 3, 2021. Thirty-five (35) of the positive cases were from western Kentucky region with the other seven spread across the state. With this group of coyotes, one hundred fifty-eight (158) were male and the other one hundred six-teen (116) were female. The estimated age ranged from a pup to senior dogs. A little over forty percent of the dogs were obtained through coyote/predator tournaments; the remaining were acquired from pest …

Exploiting The Immunomodulatory Potentials Of Inkt Cells In Sepsis And Cancer., Joshua Choi

Electronic Thesis and Dissertation Repository

Invariant natural killer T (iNKT) cells are a unique unconventional T cell subset that recognize glycolipids presented by CD1d expressing cells. The prototypical glycolipid agonist of iNKT cells, α-Galactosylceramide (α-GalCer), can induce the rapid release of an arsenal of cytotoxic effector molecules and enormous amounts of immunomodulatory cytokines as early as two hours after activation. In addition to α-GalCer, various glycolipid agonists are available that allow for specific, in vivo targeting of iNKT cells, and can exert divergent T-helper (T_H)1 and/or T_H2 immune responses. Therefore, the type of response instigated by iNKT cells can profoundly influence …

The Critical Role Of Tnf Receptors Versus Nadph Oxidase In Controlling Babesia Microti Infection, Amal Balahmar

NYMC Student Theses and Dissertations

Babesia microti is an apicomplexan parasite transmitted by tick bite that infects red blood cells. It is increasingly associated with transfusion-transmitted infections including fatal infection as the parasite survives blood banking procedures. The infection can range from asymptomatic to fatal. The parasite can persist in relatively asymptomatic individuals for up to two years. The host and parasite determinants of severity of infection and/or parasite clearance remain largely unknown. However, asplenic and immune suppressed individuals including the very young and relatively old, greater than 50 years of age, are more vulnerable to severe disease. The goal of the current research is …

The Relationship Between Glucocorticoids And The Humoral Immune Response To Mycoplasma Gallisepticum Challenges In Eastern Bluebirds, Joshua Smith

Honors Theses

Numerous studies have examined relationships between adrenal glucocorticoids and the immune system’s ability to fight disease. The relationship can vary, with glucocorticoids having either stimulatory or inhibitory effects. The pathogenic bacterium Mycoplasma gallisepticum (MG) elicits an adaptive immune response in birds, in which B cells produce MG-specific antibodies to fight the infection and prevent reoccurrence. Previous research found that Eastern Bluebirds that produce the most antibodies in response to MG infection also have the highest glucocorticoid levels. This finding led to the current study investigating whether corticosterone, the primary glucocorticoid in birds, stimulates production of antibodies in response to immune …

Evaluation Of Anthelmintic Therapies In A Fall Calving Beef Cowherd, Laine Zammit

Graduate Theses and Dissertations

Internal parasitism inevitability prompts economic loss in beef cattle production by decreasing growth performance and reproductive traits. Today, the most widely used class of anthelmintic used to treat parasitism, is the macrocyclic lactone. Many studies have conflicting results on the efficacy of macrocyclic lactones (ML) efficacy against internal parasitism. The objective of this study was to evaluate the effectiveness of moxidectin and eprinomectin, two of the MLs, on cow performance. Multiparous fall calving, crossbred beef cows (n = 106) were allocated randomly to 1 of 3 anthelmintic treatments: 1) Negative control (CON), in which cows did not receive an anthelmintic, …

Heterogeneous Nuclear Ribonucleoprotein K (Hnrnp K) Overexpression And Its Interaction With Runx1 Rna In Acute Myeloid Leukemia, Marisa Aitken

Dissertations & Theses (Open Access)

Acute myeloid leukemia (AML) is an often devastating hematologic malignancy with 5-year overall survival lingering near 20%. Acquiring a deeper understanding of molecular underpinnings of leukemogenesis will provide a basis for developing more effective therapeutic strategies for patients with AML.

Here, we identified overexpression of hnRNP K as a recurrent abnormality in a subset (~20%) of AML patients. High levels of this RNA-binding protein associated with inferior clinical outcomes in de novo AML. Thus, to evaluate its putative oncogenic capacity in myeloid disease, we overexpressed hnRNP K in murine hematopoietic stem and progenitor cells isolated from fetal liver cells (FLCs). …

Intravital Imaging In A Zebrafish Model Elucidates Interactions Between Mucosal Immunity And Pathogenic Fungi, Linda S. Archambault

Electronic Theses and Dissertations

Candida yeasts are common commensals that can cause mucosal disease and life-threatening systemic infections. While many of the components required for defense against Candida albicans infection are well established, questions remain about how various host cells at mucosal sites assess threats and coordinate defenses to prevent normally commensal organisms from becoming pathogenic. Using two Candida species, C. albicans and C. parapsilosis, which differ in their abilities to damage epithelial tissues, we used traditional methods (pathogen CFU, host survival, and host cytokine expression) combined with high-resolution intravital imaging of transparent zebrafish larvae to illuminate host-pathogen interactions at the cellular level …

Development Of A Long-Acting Nanoformulation Of Dolutegravir For Prevention And Treatment Of Hiv-1 Infection, Brady Sillman

Theses & Dissertations

Dolutegravir (DTG) is a potent human immunodeficiency virus type 1 (HIV-1) integrase strand-transfer inhibitor (INSTI) with a high barrier to viral drug resistance. However, opportunities to improve its profile abound. These include extending the drug’s apparent half-life, increasing penetrance to “putative” viral reservoirs, and reducing inherent toxicities. These highlight, in part, the need for long-acting, slow effective release antiretroviral therapy (LASER ART) delivery schemes. A long-acting (LA) DTG was made by synthesizing a hydrophobic and lipophilic prodrug encased with poloxamer (P407) surfactant. This modified DTG (MDTG) reduced systemic metabolism and polarity, increased lipophilicity and membrane permeability, improved encapsulation, and formed …

Evaluating The Effects Of Antibody-Conjugated Multi-Walled Carbon Nanotubes In Combination With Microwave Irradiation, Amy Chall

Electronic Theses and Dissertations

Cancer remains one of the largest public health concerns of our day, particularly in developed countries where technological advances have allowed populations to live well into their eighth decade. In America, those in their 80’s have a 1 in 2 chance of developing cancer in their lifetime. Prostate cancer, specifically is the second leading cause of cancer deaths in males. Traditional cancer therapies cause high levels of toxicity to the patient due to mechanisms of action that often attack cancer cells and healthy cells alike. The holy grail of cancer research is to find a treatment that targets the cancer …

Development Of A Pd-L1 Pet Imaging Biomarker, Caleb Jack Bridgwater

Posters-at-the-Capitol

Immunotherapy strategies are very promising treatments for cancer patients. Specifically, Immune checkpoint inhibitor therapy focusing on the PD-1/PD-L1 pathway shows long-lasting positive results in many cancer patients. Unfortunately, not all the patients can benefit from this highly effective treatment. Hence, there is a great need for predictive biomarkers. Immunohistochemical (IHC) staining has been used as a way of predicting patient response, yet shows many problems. For example, IHC utilizes an invasive biopsy and sample fixing, which creates an incomplete and delayed picture of the patient’s biochemistry and the tumor microenvironment, consequently ignoring metastases.

The purpose of this study is to …

Transcriptomics Of Learning, Pablo Iturralde

Theses

Learning is a basic and important component of behavior yet we have very little empirical information about the interaction between mechanisms of learning and evolution. In our work, we are testing hypotheses about the neurogenetic mechanisms through which animal learning abilities evolve. We are able to test this directly by using experimentally evolved populations of flies, which differ in learning ability. These populations were previously evolved within the lab by creating worlds with different patterns of change following theoretically predicted effects on which enhanced learning will evolve. How has evolution acted to modulate genes and gene expression in the brain …

Finding A Link Between Circadian Rhythms And The Immune System Of Captive Zebra Finches (Taeniopygia Guttata), Amber Bishop

Mahurin Honors College Capstone Experience/Thesis Projects

Circadian rhythms are commonplace in organisms and are normally controlled by a master clock. More recent evidence suggests that autonomous clocks operate in various systems in the body, including the immune system. This study looks for such a connection between the circadian rhythm and the immune system. In this study, captive zebra finches (Taeniopygia guttata) were exposed to different light and dark cycles and blood samples were taken every six hours. Birds were exposed to 12 hours of light and then 12 hours of darkness (LD), 24 hours of darkness (DD), or 48 hours of DD. After collecting …

Lymphoid Hematopoiesis And The Role Of B-Cells In Transgenic Mouse Model Of Sickle Cell Disease, Christina Cotte

University Scholar Projects

Sickle cell disease (SCD) has been shown to be associated with decreased baseline immunity and thus increased susceptibility to infection. I sought to discern possible causes of this by looking into the correlations between SCD and hematopoiesis, the immune system and the neuroendocrine system, and ultimately by conducting experiments surrounding the impaired immune system of SCD. These experiments focused on the potential causes and effects of the diminution of B-1a cells in the SCD spleen. Adoptive transfers, infections with Streptococcus pneumoniae, and histologic imaging were conducted to establish if the diminution of the B-1a cells in the SCD spleen …

Effects Of Chromium On Mouse Splenic T Lymphocytes And Effects Of Ethanol Exposure During Early Neurodevelopment On Behaviors In Mice, Lu Dai

Theses and Dissertations--Toxicology and Cancer Biology

The dissertation consists of three major projects with the focus on the immunotoxicity of chromium and the behavior disorders caused by early ETOH exposure respectively.

Hexavalent chromium [Cr(VI)] is widely used in various industrial processes and has been recognized as a carcinogen. As the first line of host defense system, the immune system can be a primary target of Cr(VI). T cell population represents a major arm of the immune system that plays a critical role in host anti-tumor immunity. Dysfunction of T cells compromises host anti-tumor immunity resulting in oncogenesis. Using mouse splenic T cells as an in vitro …

Effects Of Spaceflight On Phagocytic Function And Immune-Neural Interaction, Farnaz P. Baqai

Loma Linda University Electronic Theses, Dissertations & Projects

In spaceflight, astronauts will be exposed to several environmental risk factors that may lead to disturbances in homeostasis maintained by the central nervous system (CNS) and immune system. Low Earth orbit (LEO) spaceflight studies have shown that microgravity changes virtually all immune parameters that have been evaluated. Similarly, ground based studies have shown that low-dose radiation can also significantly impact immune function. Finally, as most spacecrafts are ecologically and environmentally closed systems, astronauts may be at increased risk for exposure to aerosolized infectious agents. The hypothesis of this study is: Exposure to spaceflight environment (microgravity and radiation) can influence immune …