Life Sciences Commons^™

Characterizing The Interaction Between Human Adenovirus E1a And Sting, Jessica Hill

Electronic Thesis and Dissertation Repository

When challenged by viral DNA, the cytoplasmic DNA sensor cyclic GMP-AMP synthase (cGAS) signals through the adaptor protein stimulator of interferon genes (STING) to induce a primary type I IFN response. Studies from recent years have also revealed shared architecture between metabolism and innate immunity. Viruses have evolved to counteract these mechanisms. Human adenovirus (HAdV) early region 1A (E1A) protein antagonizes the cGAS-STING pathway to prevent an innate immune response by physically interacting with STING. I hypothesize that the interaction between E1A and STING is mediated through several motifs and involves ribosomal protein S6 kinase beta-1 (S6K1). Using a series …

Immune Responses To Homocitrulline- And Citrulline-Containing Peptides In Rheumatoid Arthritis, Patrick Lac

Electronic Thesis and Dissertation Repository

Anti-citrulline immune responses contribute to rheumatoid arthritis (RA) development, and are linked with the expression of HLA-DR molecules that encode the Shared Epitope (SE). Immune responses to homocitrulline, a structural analog of citrulline, have been recently detected in RA, but their role in RA is unknown.

The objectives of this study were to examine the specificity of anti-homocitrulline antibodies for RA, the dependence of anti-homocitrulline responses on SE-expression, and the cross-reactivity of responses to homocitrulline and citrulline. These objectives were addressed in RA patients and in SE-expressing DR4tg mice using homocitrulline- and citrulline-rich peptides.

Anti-homocitrulline antibodies occurred specifically in RA. …

Evolutionary Genetic Aspects Of Host Association In Generalist Ectoparasites, Benoit Talbot

Electronic Thesis and Dissertation Repository

Despite the use of the host for dispersal by most parasite species, the extremely loose relationship typical between highly mobile hosts and generalist ectoparasites may lead to very different gene flow patterns between the two, leading in turn to different spatial genetic structure, and potentially different demographic history. I examined how similar gene flow patterns are between Cimex adjunctus, a generalist ectoparasite of bats present throughout North America, and two of its key bat hosts. I first analyzed the continent-scale genetic structure and demographic history of C. adjunctus and compared it to that of two of its hosts, the …

Characterizing Ferroportin Trafficking In Macrophages During Phagocytosis, Tayler J. Farrell

Electronic Thesis and Dissertation Repository

Macrophages are important mediators of innate immunity and nutritional immunity via modulation of essential nutrients like iron during bacterial infection. Ferroportin (Fpn), an iron-exporting protein, is found on the plasma membrane of macrophages and, if not modulated during phagocytosis, would transport iron into phagosomes and supply phagocytosed bacteria with iron. Interestingly, the fate of Fpn during phagocytosis and bacterial infection remains unknown. We generated a Fpn-GFP fusion protein and, using fluorescence microscopy, demonstrated that, during phagocytosis in RAW264.7 macrophages, Fpn is removed from phagosomes containing IgG-coated beads or Staphylococcus aureus. Further, Fpn is present on Rab5-containing phagosomes but absent …

Evaluating Evolving Leukocyte Populations In Peripheral Blood Circulation Post-Concussion In A Human Longitudinal Analysis Of Female Athletes, Kevin A. Blackney

Electronic Thesis and Dissertation Repository

Concussions are generating increasing concern due to potential long-term neurological consequences. Currently there is no universally recognized diagnostic approach for concussion. I hypothesize that a signature temporal response of biomarkers of inflammation in systemic circulation will provide an objective diagnosis of concussion and could also be used to track patient recovery. The Western University women’s rugby team underwent blood draws at pre-season and post-season as a baseline evaluation, and players determined to have sustained a concussion underwent repeat blood analysis post-concussion. Blood samples were analyzed by flow cytometry to profile immune cell populations alongside accepted concussion assessments, and complete blood …

Superantigen Responsive T Cells Are Required For Nasopharyngeal Infection By Streptococcus Pyogenes, Joseph J. Zeppa

Electronic Thesis and Dissertation Repository

Streptococcus pyogenes is a human-specific pathogen that is responsible for serious morbidity and mortality worldwide despite being susceptible to common antibiotics. Furthermore, there is currently no licensed vaccine available against this organism. Previous research from our laboratory implicated a critical role for SAgs in a transgenic mouse model of acute nasopharyngeal infection by S. pyogenes. Herein, we are able to detect SAg production in vivo and establish that anti-SAg antibodies generated by either passive immunization or active vaccination with a MHC II-binding interface SAg toxoid reduces S. pyogenes nasopharyngeal burden. We were also able to demonstrate that this organism …

P23. Elucidation Of The Signaling Pathway Of Mertk, Kyle Taruc

Western Research Forum

Background

Mer Tyrosine Kinase (MERTK) is a receptor which mediates efferocytosis – removal of apoptotic cells by phagocytes such as macrophages. MERTK plays a critical role in homeostasis, with mutations in MERTK associated with the development and progression of atherosclerosis, the buildup of cholesterol-laden plaque in the sub-arterial space. Indeed, one MERTK allele is associated with 66% (heterozygous) to 75% (homozygous) protection from atherosclerosis, while other alleles and SNP’s pre-dispose to atherosclerosis and autoimmunity. Complications resulting from atherosclerosis, including heart attack and stroke, are currently the second leading cause of mortality in Canada. Despite the importance of MERTK in atherosclerosis …

Pulmonary Surfactant Fortified With Cath-2 As A Novel Therapy For Bacterial Pneumonia, Brandon J. Baer

Western Research Forum

Background: Bacterial pneumonia is a leading cause of death worldwide, with high mortality rates persisting even after antibiotic treatment. Current treatments for pneumonia involve administration of antibiotics, however after the bacteria are killed they release toxic substances that induce inflammation and lung dysfunction. Host defense peptides represent a potential solution to this problem through their ability to down regulate inflammation. However, effective delivery to the lung is difficult because of the complex branching structure of the airways. My study addresses this delivery problem by using exogenous surfactant, a pulmonary delivery vehicle capable of improving spreading of these peptides throughout the …

Rapid Regulatory And Effector Immune Responses In Toxic Shock Syndrome, Peter Anthony Szabo

Electronic Thesis and Dissertation Repository

Toxic shock syndrome (TSS) is an acute, potentially fatal condition characterized by high-grade fever, hypotensive shock and systemic inflammation. It is caused by exposure to staphylococcal and streptococcal superantigens (SAgs), which can activate up to 50% of T cells resulting in a hyperinflammatory ‘cytokine storm’ within hours. This inflammatory cascade progresses to a life-threatening illness with alarming rapidity, and SAg-exposed individuals can develop multi-organ failure within hours of onset of symptoms. However, there are currently no available treatments that efficiently mitigate the cytokine storm, which drives TSS immunopathology. Therefore, identifying and understanding the critical components underlying this process should hold …

Thermal Biology Of Insect Immunity And Host-Microbe Interactions, Laura V. Ferguson

Electronic Thesis and Dissertation Repository

The influence of temperature on interactions with pathogenic or symbiotic microbes is a driving force behind the survival of insects under climate change. However, we know little of how insects physiologically respond to these pressures. In temperate climates, winter dominates the thermal landscape; thus, I am particularly interested in how cold interacts with insect responses to microbes. Here I explore the thermal biology of the insect immune system and the impacts of cold on host-microbe interactions. First, I demonstrate that acute exposure to cold activates selective components of immunity in Drosophila melanogaster, as a compensatory response to trade-offs or …

Mhc Class Iiβ Diversity As A Correlate Of Neutral-Locus Similarity And Diversity, And A Predictor Of Overwinter Return, In Song Sparrows (Melospiza Melodia), Matthew J. Watson

Electronic Thesis and Dissertation Repository

Abstract

The major histocompatibility complex (MHC) is a family of genes involved with recognizing pathogens and mounting an immune response. Parasite-mediated selection often favours heterozygosity at MHC because MHC-diverse individuals recognize a wider range of pathogens. Because migratory birds encounter many pathogens, I hypothesized that MHC diversity predicts overwinter and juvenile survivorship in song sparrows (Melospiza melodia). I found no correlation between MHC diversity and neutral-locus (microsatellite) heterozygosity, suggesting that measures of neutral and adaptive genetic diversity provide complementary rather than redundant information. However, pairwise similarity at MHC predicted pairwise similarity at microsatellite loci. In contrast to my hypothesis, MHC …