Immunology and Infectious Disease Commons^™

Temporal, Phenotypic, And Quantitative Characterization Of Thyroid Infiltrating Mononuclear Cells During Development Of Spontaneous Autoimmune Thyroiditis In Obese Strain Chickens, Katelyn M. Clark

Poultry Science Undergraduate Honors Theses

The Obese strain (OS) of chickens spontaneously develops autoimmune thyroiditis and is a well-established biomedical model for Hashimoto’s thyroiditis in humans. Both conditions are characterized by the infiltration of the thyroid glands with mononuclear cells resulting in destruction of the thyroid tissue and impairment of the thyroid’s endocrinological functions. Past studies have described mononuclear cell infiltration in thyroids of the OS chickens, but the time-course, cell composition, and relative amounts of the various mononuclear cells infiltrating the thyroids has not been well defined. In this project, the mononuclear cell infiltrate was characterized phenotypically and quantitatively in OS chickens over the …

Immunomodulatory Effects Of Resolvin D2 In A Model Of Infection, Prem Yugandhar Kadiyam Sundarasivarao

Graduate School of Biomedical Sciences Theses and Dissertations

Dysregulated hyperinflammatory host immune response to underlying bacterial infections is a characteristic of sepsis. In sepsis, bacteria often trigger abnormal hyperinflammatory responses which can cause multiple organ failure and if sustained can lead to an immunosuppressive phase where the host is susceptible to secondary infections caused by opportunistic bacteria like Pseudomonas aeruginosa (P. aeruginosa). In our studies, we used a 2-hit model of cecal ligation and puncture (CLP) followed by P. aeruginosa secondary lung infection to investigate cellular and molecular mechanisms in the beneficial action of resolvin D2 (RvD2). Resolvins of the D-series are a group of fatty acids known …

Rapid & Sensitive Detection Of Antibiotic Resistance Genes By Utilizing New Diagnostic Probe Tales With 2d-Nanosheet Graphene Oxide, Jihye Kang

Masters Theses & Specialist Projects

As antibiotic resistance is one of the major health concerns in infectious diseases because of reducing the efficacy of antibiotics, rapid and sensitive detection of antibiotic resistance genes is critical for the effective treatment of infectious diseases. Polymerase chain reaction (PCR) is widely used to detect nucleic acids, but it requires additional steps involved in DNA denaturation and subsequent hybridization. A new class of DNA-binding domains called transcriptional activator-like effectors (TALEs) provide a novel scaffold for designing versatile DNA-binding proteins due to their modularity and predictability. Here, we developed a simple, rapid, and sensitive system for detecting antibiotic resistance genes …

Prevalence Of Ehrlichia And Rickettsia Within Ticks In Arkansas State Parks, Haley Stanton

Animal Science Undergraduate Honors Theses

Within the past few decades, the number of diagnoses of tick-borne diseases – such as spotted fever rickettsiosis and ehrlichiosis – has steadily increased throughout the United States, with Arkansas having one of the highest rates in the country. These diseases pose a risk to both humans and animals, as both can acquire these infections from ticks. Due to the increasing geographic range of ticks, rise in cases, and likely underdiagnosis of these diseases, this study aimed to identify the infection rate of ticks themselves in multiple state parks in Arkansas. Four Arkansas state parks were each visited once a …

Roles For Mycobacterial Dinb2 In Frameshift And Substitution Mutagenesis, Pierre Dupuy, Shreya Ghosh, Allison Fay, Oyindamola Adefisayo, Richa Gupta, Stewart Shuman, Michael S. Glickman

Publications and Research

Translesion synthesis by translesion polymerases is a conserved mechanism of DNA damage tolerance. In bacteria, DinB enzymes are the widely distributed promutagenic translesion polymerases. The role of DinBs in mycobacterial mutagenesis was unclear until recent studies revealed a role for mycobacterial DinB1 in substitution and frameshift mutagenesis, overlapping with that of translesion polymerase DnaE2. Mycobacterium smegmatis encodes two additional DinBs (DinB2 and DinB3) and Mycobacterium tuberculosis encodes DinB2, but the roles of these polymerases in mycobacterial damage tolerance and mutagenesis is unknown. The biochemical properties of DinB2, including facile utilization of ribonucleotides and 8-oxo- guanine, suggest that DinB2 could be …

A Novel Neuroinvasive Infection Modality For Francisella Tularensis Elicits Neuroinflammation Resulting In Cellular Damage, Mireya Griselle Ramos-Muniz

Open Access Theses & Dissertations

Francisella tularensis (Ft.) is a gram-negative coccobacillus bacterium that causes the zoonotic disease tularemia in humans. Ft. causes the most severe, often fatal, form of the disease through inhalation. However, Ft. is most commonly transmitted through direct contact with infected animal carcasses such as rodents and rabbits, consumption of contaminated food or water, or through arthropod bites, particularly ticks. Due to its extremely low infectious dose, high mortality rate, and potential use as a biological warfare agent, Ft. is classified by the CDC as a "Tier 1 select agent". Ft. infection triggers an overactive inflammatory response, termed a "cytokine storm", …

Sex Differences In Host Resistance And Tolerance To The Common Avian Pathogen Mycoplasma Gallisepticum, Chloe Connelly

Biological Sciences Undergraduate Honors Theses

As we face the threat of global pandemics, one thing becomes clear: biological research is not just about the pursuit of the unknown, but about protecting our future. Understanding disease transmission and predicting pathogen epidemics is more important than ever. Prior studies have indicated that in populations where one sex engages in more social behaviors and movement that sex may drive disease transmission. This supports sex as a factor to consider in the study of epidemic dynamics. Host physiology and immune strategies are another factor that can influence epidemics. Two commonly examined strategies are tolerance and resistance. Tolerance is the …

Effects Of Cyclic Heat Stress On The Acute Inflammatory Response In Broilers, Alessandro J. Rocchi

Poultry Science Undergraduate Honors Theses

Heat stress (HS) is a growing concern in broiler production due to increasing environmental temperatures. Little is known of the overall effect of HS on innate immunity. Lipopolysaccharide (LPS), an outer membrane component of Gram-negative bacteria, is commonly used to study the inflammatory response. In avian species, the local tissue and systemic inflammatory activities in response to LPS may be determined concurrently, over time, in an individual, using the growing feather (GF) pulp dermal test along with blood measurements (dual-window approach). To examine the effect of cyclic HS on the local and systemic acute inflammatory responses, Cobb 500 male broiler …

Osteoimmunology And The Reconstruction Of Host Immunological Status In Treponemal Infection: Effect Of Activated Immune Cells By Oral Pathogens And Treponema Pallidum On Osteoclastogenesis., Michayla Gatsos

College of Arts & Sciences Senior Theses

Syphilitic infection caused by bacterium Treponema pallidum pallidum (Tp) offers an excellent model to study the long-lasting interplay between the immune and skeletal systems and could be used to reconstruct host immunological status. We propose that a hyper-inflammatory phenotype developed during acquired syphilis will have a systemic impact on most bone microenvironments involving inflammatory processes, such as the one developed in periodontal disease (PD). Using osteoimmunological in vitro protocols, we explore whether immune activation by Tp antigens and PD pathogens can impact osteoclastogenesis (OCG), ultimately helping to understand the bone alterations caused by systemic inflammatory processes in skeletal material. We …

Effects Of Maternal Disease History On Provisioning, Brooding, And Offspring Outcomes, Sakura Roberts

Biological Sciences Undergraduate Honors Theses

Disease within a population has the ability to shape the development, evolution, and general performance of a species. Pathogen exposure to hosts can influence their physiology and behavioral patterns to further shape offspring immunity. Parental conditions experienced by offspring during early development can benefit survival and fitness (e.g. increasing provisioning rates), as well as help deter against similar diseases experienced by parents. By testing if parental behavior changes can better prepare offspring outcomes for disease exposure, such as disease severity or duration of infection, we can see the beneficial impacts it has on disease dynamics and host-pathogen processes. Incubation temperature, …

Potency Of Novel Anti-Toxoplasmic Compounds, Matthias Walters

Theses/Capstones/Creative Projects

Toxoplasma gondii, the causative agent of toxoplasmosis, is an intracellular apicomplexan parasite. Toxoplasmosis is often asymptomatic, though, it can be debilitating or fatal to immunocompromised individuals and fetuses, being one of the leading causes of fetal mortality and birth defects. Toxoplasmosis is treated with a synergistic combination of drugs pyrimethamine and sulfadiazine; however, these drugs are only effective against the acute stage of infection, and the pyrimethamine is relatively cytotoxic, damaging bone marrow and causing noxious side effects. Due to these limitations, a safer alternative that targets the chronic stage of infection is needed. In this study, we tested …

Investigating Novel Chemotherapeutics Against The Parasite Toxoplasma Gondii, Braydon Dreher

Theses/Capstones/Creative Projects

Toxoplasma gondii, an intracellular protozoan, is a globally prevalent parasite due to the infectivity of T. gondii with nearly 2.5 billion people affected worldwide. Toxoplasma gondii can cause toxoplasmosis, which is a disease acquired through the consumption of undercooked meat or found in the feces of felines, and often leads to profound neuropathology and potentially death. Currently, acute toxoplasmosis is treated with pyrimethamine and sulfadiazine, which is a combination of an antiprotozoal and a sulfonamide. This combination of drugs directly targets the acute stage of infection but has failed to eliminate or impact the chronic carriage of bradyzoites while …

Elucidating Mechanisms Involved In Host Microbial-Tumor Interactions, Vidhi Chandra

Dissertations and Theses (Open Access)

Cancer is a rising cause of mortality worldwide. Microbiota is the collection of micro-organisms that live inside our bodies and can impact the host health and disease by interacting with the immune and metabolic systems. The relationship between the microbiota and cancer is complex. Gut and intratumoral microbiota can affect cancer development and progression by influencing patient outcomes and therapy responsiveness in several cancer types. Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer surrounded by a highly immuno-suppressive tumor microenvironment (TME) which limits efficacy of most available therapies. The tumoral niche provides a privileged microenvironment for microbial colonization that can …

Oncolytic Virus Immunotherapy: Development And Potential For Cancer Treatment, Olivia Guinness

Honors Scholar Theses

The American Cancer Society estimates that in 2023, 1,958,310 new cancer cases and 609,820 cancer deaths will occur in the United States [16]. A promising therapeutic option that has been supported by recent clinical trials is the use of oncolytic viruses to treat malignant tumors. The mechanism of action of existing treatments, such as chemotherapy, radiotherapy, and surgery, differs from that of oncolytic virus therapy because oncolytic viruses are able to affect cancer cells with specificity, minimizing side effects. When infecting a normal, non-cancerous cell, oncolytic viruses do not replicate, leaving healthy cells unaffected. In tumor cells, oncolytic viruses will …

Life Stressors And Immune Aging: Protective Effects Of Cognitive Reappraisal, Rebecca G. Reed, Steven R. Presnell, Ahmad Al-Attar, Charles T. Lutz, Suzanne C. Segerstrom

Markey Cancer Center Faculty Publications

Stressful life events may accelerate aspects of immune aging, but habitual use of an adaptive emotion regulation strategy, cognitive reappraisal, may attenuate these effects. This study examined whether cognitive reappraisal moderates the associations between life stressor frequency and stressor desirability on aspects of immune aging, including late-differentiated CD8+ T and natural killer (NK) cells and inflammatory markers (IL-6, TNF-α, and CRP), both between and within people in a longitudinal sample of 149 older adults (mean age = 77.8, range: 64–92 years). Participants reported stressful life events, use of cognitive reappraisal, and provided blood semiannually for up to 5 years to …

Comparative Characteristics Of Integrin Αdβ2 Binding To Native Fibrinogen And Fibrinogen Modified By Dha Oxidation During Inflammation, Ajibola Ilesanmi

Electronic Theses and Dissertations

2-ω-carboxyethylpyrrole (CEP) is a product of docosahexaenoic acid (DHA) oxidation, which forms covalent adducts with different proteins. CEP-modified proteins can interact with macrophage receptor, integrin αDβ2. This study aims to compare αDβ2 binding to its physiological ligand, fibrinogen, and CEP-modified fibrinogen, which is formed during inflammation. We hypothesize that modification of fibrinogen changes its ligand-binding properties to integrin αDβ2 which can affect macrophage migration and retention. Recombinant αD I-domain and αDβ2-transfected HEK293 cells were used for the experiments. Using biolayer interferometry, we found that the affinity of αD I-domain binding to fibrinogen-CEP was higher than fibrinogen and inhibited by the …

Investigating The Roles Of Lung Epithelial Stat3 In Therapeutically Inducible Resistance To Acute Bacterial Pneumonia., Vikram V. Kulkarni, Vikram V. Kulkarni

Dissertations and Theses (Open Access)

Investigating the roles of lung epithelial STAT3 in therapeutically inducible resistance to acute bacterial pneumonia.

Vikram Vitthal Kulkarni, M.S.

Advisory Professor: Scott Evans, MD.

The lung epithelium is a dynamic tissue capable of displaying structural and functional plasticity in response to pathogenic challenges. Our lab has demonstrated that it is possible to therapeutically exploit the lung epithelium’s versatility by inducing resistance to lethal pneumonias caused by viruses, bacteria and fungi. An inhaled combination of a TLR2/6 agonist and a TLR9 agonist (Pam2ODN) results in robust protection against otherwise lethal pneumonia caused by Pseudomonas aeruginosa. Pam2ODN-mediated protection requires key signaling …

The Cx3cl1-Cx3cr1 Chemokine Axis Contributes To Tumor Immune Evasion And Its Blockade Enhances Responses To Anti-Pd-1 Immunotherapy, Apoorvi Chaudhri

Dissertations and Theses (Open Access)

CX3CL1 secreted in the tumor microenvironment serves as a chemoattractant playing a critical role in metastasis of CX3CR1 expressing cancer cells. While CX3CR1 can be expressed in both cancer and immune-inhibitory myeloid cells to facilitate their migration, the mechanisms employed by this axis on these cells to mediate immune suppression remain poorly understood. Here, we explore the immune evasion strategies implemented by this axis and find that it initiates a resistance program in cancer cells that results in 1) facilitation of tumor cell migration, 2) secretion of soluble mediators to generate a pro-metastatic niche, 3) secretion of mediators to attract …

Uncovering Molecular Targets To Overcome Immunosuppression In Non-Small Cell Lung Cancer With Acquired Tki Resistance, Sonia A. Patel

Dissertations and Theses (Open Access)

Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related deaths worldwide. Targeted therapeutic agents, such as epidermal-like growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) or monoclonal antibodies targeting vascular endothelial growth factor (VEGF/R), can effectively inhibit upregulated signaling pathways driving tumorigenesis in NSCLC and many other cancers. Unfortunately, however, resistance to such targeted therapies inevitably arise in most patients and can occur through a variety of resistance mechanisms including genomic alterations and upregulation of bypass pathways. Additionally, patients who have acquired resistance to these targeted agents typically have tumors characterized by an immunosuppressive tumor microenvironment and thus …

Kir-Based Inhibitory Cars Overcome Car-Nk Cell Trogocytosis-Mediated Fratricide And Tumor Escape, Ye Nmn Li

Dissertations and Theses (Open Access)

Trogocytosis is an active process that transfers surface material from targeted to effector cells. Using multiple in vivo tumor models and clinical data, we report that chimeric antigen receptor (CAR) activation in natural killer (NK) cells promoted the transfer of the CAR-cognate-antigen from tumor to NK cells, resulting in (1) lower tumor antigen density, thus impairing the ability of CAR-NK cells to engage with their targets, (2) induced self-recognition and continuous CAR-mediated engagement, resulting in fratricide of trogocytic antigen expressing NK cells (NK^TROG+) and NK cell hyporesponsiveness. This phenomenon could be offset by a dual-CAR system incorporating both …

Adipocytes And Innate Immunity In Systemic Sclerosis, Nancy Wareing

Dissertations and Theses (Open Access)

Systemic sclerosis (SSc; scleroderma) is a chronic systemic autoimmune and connective tissue disorder characterized by vasculopathy, autoimmune phenomena, and widespread fibrosis. Skin thickening and tightening is the cardinal feature of SSc and is responsible, in part, for the considerable morbidity of this disease. There are currently no targeted treatments for skin manifestations in SSc, primarily due to our fragmented understanding of its pathophysiologic mechanisms. In PART I, we report a previously unappreciated link between aberrant expression of the developmental gene sine oculis homeobox homolog 1 (SIX1) in skin-associated adipocytes in SSc skin and the early loss of dermal white adipose …

Hypoxia Activated Prodrug And Anti-Angiogenic Therapy Cooperate To Treat Pancreatic Cancer But Elicit Immune Suppressive G-Mdsc Infiltration, Arthur Liu

Dissertations and Theses (Open Access)

We previously showed that the hypoxia-activated prodrug TH-302 (Evofosfamide) reduces intratumoral hypoxia through a tissue remodeling process, initiates tumor vasculature reorganization, and sensitizes aggressive, spontaneous murine models of prostate cancer to immune checkpoint blockade (ICB). In a clinical trial testing the combination of TH-302 with cytotoxic T-lymphocyte-associated protein (CTLA-4) blockade (NCT03098160) a subset of metastatic, ICB refractory patients showed prolonged progression free survival. While these studies highlight hypoxia as therapeutically tractable, we lack a complete understanding of the contribution of the tumor vasculature to hypoxia reduction therapy, as well as the downstream consequences of hypoxia reduction on the cellular composition …

Preclinical Evaluation Of Immunomodulatory Effects Of Aurora Kinase Inhibition In Human Papillomavirus Positive Cancers, Pragya Sinha

Dissertations and Theses (Open Access)

Human papillomavirus (HPV) is the causative agent of cervical cancer and some cancers of the penis, vulva, vagina, anus, and oropharynx. Current therapies for these cancers include a combination of surgery, radiotherapy, and chemotherapy that often results in permanent, life altering adverse effects. Immunotherapy is partially effective, but with significant recurrence and lower long-term survival. Importantly, there are no few biomarker-selective targeted therapies for these cancers. To address this unmet need, our collaborators conducted a large-scale drug screen and identified Aurora Kinase (AK) inhibitors as a unique class of reagents to induce selective apoptosis in HPV+, but not HPV- human …

Translational Studies Using The Malt1 Inhibitor (S)-Mepazine To Induce Treg Fragility And Potentiate Immune Checkpoint Therapy In Cancer, Mauro Di Pilato, Yun Gao, Yi Sun, Amina Fu, Carina Grass, Thomas Seeholzer, Regina Feederle, Irina Mazo, Samuel W Kazer, Kevin Litchfield, Ulrich H Von Andrian, Thorsten R Mempel, Russell W Jenkins, Daniel Krappmann, Peter Keller

Faculty, Staff and Student Publications

Introduction

Regulatory T cells (Tregs) play a critical role in the maintenance of immune homeostasis but also protect tumors from immune-mediated growth control or rejection and pose a significant barrier to effective immunotherapy. Inhibition of MALT1 paracaspase activity can selectively reprogram immune-suppressive Tregs in the tumor microenvironment to adopt a proinflammatory fragile state, which offers an opportunity to impede tumor growth and enhance the efficacy of immune checkpoint therapy (ICT).

Methods

We performed preclinical studies with the orally available allosteric MALT1 inhibitor (S)-mepazine as a single-agent and in combination with anti-programmed cell death protein 1 (PD-1) ICT to …

Targeting Pd-L2-Rgmb Overcomes Microbiome-Related Immunotherapy Resistance, Joon Seok Park, Francesca S Gazzaniga, Meng Wu, Amalia K Luthens, Jacob Gillis, Wen Zheng, Martin W Lafleur, Sarah B Johnson, Golnaz Morad, Elizabeth M Park, Yifan Zhou, Stephanie S Watowich, Jennifer A Wargo, Gordon J Freeman, Dennis L Kasper, Arlene H Sharpe

Faculty, Staff and Student Publications

The gut microbiota is a crucial regulator of anti-tumour immunity during immune checkpoint inhibitor therapy. Several bacteria that promote an anti-tumour response to immune checkpoint inhibitors have been identified in mice1-6. Moreover, transplantation of faecal specimens from responders can improve the efficacy of anti-PD-1 therapy in patients with melanoma7,8. However, the increased efficacy from faecal transplants is variable and how gut bacteria promote anti-tumour immunity remains unclear. Here we show that the gut microbiome downregulates PD-L2 expression and its binding partner repulsive guidance molecule b (RGMb) to promote anti-tumour immunity and identify bacterial species that mediate this effect. PD-L1 and …

Sars-Cov-2 Serostatus And Covid-19 Illness Characteristics By Variant Time Period In Non-Hospitalized Children And Adolescents, Sarah E Messiah, Michael D Swartz, Rhiana A Abbas, Yashar Talebi, Harold W Kohl, Melissa Valerio-Shewmaker, Stacia M Desantis, Ashraf Yaseen, Steven H Kelder, Jessica A Ross, Lindsay N Padilla, Michael O Gonzalez, Leqing Wu, David Lakey, Jennifer A Shuford, Stephen J Pont, Eric Boerwinkle

Faculty, Staff and Student Publications

OBJECTIVE: to describe COVID-19 illness characteristics, risk factors, and SARS-CoV-2 serostatus by variant time period in a large community-based pediatric sample.

DESIGN: Data were collected prospectively over four timepoints between October 2020 and November 2022 from a population-based cohort ages 5 to 19 years old.

SETTING: State of Texas, USA.

PARTICIPANTS: Participants ages 5 to 19 years were recruited from large pediatric healthcare systems, Federally Qualified Healthcare Centers, urban and rural clinical practices, health insurance providers, and a social media campaign.

EXPOSURE: SARS-CoV-2 infection.

MAIN OUTCOME(S) AND MEASURE(S): SARS-CoV-2 antibody status was assessed by the Roche Elecsys

RESULTS: Over half …

Prevalence Of Dog Heartworm (Dirofilaria Immitis) Infection In Invasive Aedes Aegypti And Aedes Albopictus Mosquitoes In Southern California, Irene Hui Ying Lee, Donghwi Kim, Romina Lee

Pacific Undergraduate Research and Creativity Conference (PURCC)

No abstract provided.

Ramsay Hunt Syndrome With Oral Findings: A Rare Case, İlknur Eninanç, Büşra Şahin

Journal of Dentistry Indonesia

Ramsay Hunt syndrome (RHS) is a disease that is caused by the varicella-zoster virus and is characterized by severe ear pain, auricular vesicular eruptions, and peripheral facial paralysis.

Objective: The aim of this case report is to provide information about the clinical findings and treatment process of RHS, which is a rare case and may have oral findings and stress the importance of early diagnosis.

Case Report: A 60-year-old male patient had previously consulted an otolaryngologist and a family physician with complaints of vesicular eruptions in the right ear auricle and on the mandible. The patient in whom a diagnosis …

White Blood Cell Make Up In Kellback Snake Offspring Of Varying Maternal Size, Angelica Mccoy

Symposium of Student Scholars

The immune system is composed of various organs, systems, and other components with one of the most important being white blood cells. White blood cells are commonly separated into two scientific varieties, granulocytes and agranulocytes, which can be differentiated by the presence or absence of granules in the cytoplasm once stained on a slide. There are three granulocytes and two agranulocytes, each with a distinct function and shape. The ratio of these may impact the effectiveness of this portion of the immune system, and multiple factors could play a role in this ratio, an example being the size of an …

Functional Domains Of The Hsv-1 Ul37 Protein In Virus Infectivity And Retrograde Transport In Neurons, Carolyn Clark

LSU Doctoral Dissertations

Herpes simplex virus type 1 is large alphaherpesvirus with 20 envelope proteins and 23 tegument proteins. Virus entry is via fusion of the viral envelope with cellular membranes mediated by a complex of viral glycoproteins. Glycoprotein B (gB) is the only fusogenic glycoprotein, while other viral glycoproteins and membrane proteins including gD, gH, gL, gK and UL20 membrane protein modulate gB’s fusogenicity. Previously, Our laboratory developed the HSV-1 (VC2) vaccines strain with partial deletions in the amino termini of gK (ΔgK(31–68)) and the UL20 membrane protein (ΔUL20(4–22)). VC2 enters epithelial cells only via endocytosis followed by release of the capsid …