Immunology and Infectious Disease Commons^™

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, …

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 …

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 …

A Study Of Immune-Regulation Of Microbiota Supernatant On Macrophage Function, An N. Nguyen

Master's Theses

The diverse human microbial ecosystem colonizes many different body sites. The gastrointestinal (GI) tract, especially, is a major region that that harbors a complex microbial community composed of trillions of commensal bacteria. Interactions between the commensal bacteria and the host immune system begin at birth and continue through the human lifespan. In the gut, commensal bacteria help the host to ensure the maintenance of intestinal homeostasis as well as the mucosal barrier structure through host stimulation of mucus and antimicrobial molecules. The secretion of these host factors functions to inhibit pathogenic invasion and maintain the population of commensal bacteria. The …

Characterization Of Il-22-Producing Cells In The Human Thymus And The Mechanism By Which Il-22 Expression Is Modulated By Thymic Epithelial Cells., Nadine N. Morgan

Master's Theses

Thymic epithelial cells (TECs) are indispensable for T cell development and maturation. Therefore, damages to the thymic epithelial cells are detrimental to thymic function and immune response. In young healthy individuals, TECs have a high regenerative potential and are capable of renewal from serious damage; however, the molecular mechanism of this recovery is unclear. A recent study has shown that IL-22-producing ILCs are present in the mouse thymus and can regenerate thymic epithelial cells following radiation induced injuries. However, it is unknown whether IL-22-producing cells are also found in the human thymus. Thus, the goal of this study is to …

Defining The Role Of A Putative Peptidase In Staphylococcus Aureus Quorum Sensing And Pathogenesis, Chelsea Rose White

Master's Theses

The pathogenic bacterium Staphylococcus aureus encounters a variety of immune cells that restrict bacterial growth and dissemination during infection. However, S. aureus counters these immune cell functions by producing myriad virulence factors that facilitate evasion of host defenses. Therefore, it is important to understand S. aureus-immune cell interactions and the virulence factors that perturb normal immune function to promote pathogenesis. In a genetic screen designed to identify S. aureus secreted factors that modulate macrophage activity our lab identified a transposon insertion mutant in the gene SAUSA300_1984, encoding a putative membrane spanning peptidase. To investigate the role of 1984 in pathogenesis, …

Detection Of Hcmv Viral Il-10 (Vil-10) In Healthy Blood Donors, Vivian P. Young

Master's Theses

Human cytomegalovirus (HCMV) is widespread in the general population and can establish lifelong latency with expression of a limited subset of viral genes. The UL111A gene is expressed during both lytic and latent infection, and at least two protein isoforms are produced. During lytic infection, the full length transcript yields cmvIL-10, a potent immunosuppressive viral ortholog of human IL-10 (hIL-10). Alternative splicing of the UL111A transcript yields a truncated protein, LAcmvIL-10, which is expressed during both lytic and latent infection but with a limited range of immunosuppressive functions. The two viral cytokines, collectively termed viral IL-10 (vIL-10), are identical in …

Characterization Of Exopolysaccharide (Eps) Produced By Bacillus Subtilis Mutants, Alexander Argianas

Master's Theses

Bacillus subtilis is a probiotic bacterium that can protect against the murine-

specific attaching and effacing (A/E) pathogen Citrobacter rodentium. C. rodentium displays many features observed with the human pathogen enteropathogenic E. coli (EPEC). Protection by B. subtilis is mediated by exopolysaccharide (EPS), which is encoded by the epsA-O operon that contains 15 genes. Disruption of one of these genes, epsH, which appears to encode a putative glycosyltransferase, leads to the loss of protective capacity by B. subtilis and by EPS. EPS is a major component of the B. subtilis biofilm and the ΔepsH mutant is unable to form a …

Role Of Heat Shock Proteins In Maintenance Of The Gut Barrier Following Burn Injury, Abigail Rhea Cannon

Master's Theses

Introduction: Burn injury remains a prominent clinical problem. Patients suffering from burns often succumb to secondary infectious complications leading to sepsis and widespread tissue injury ending in Multiple Organ Dysfunction. However, the mechanism behind the onset of these extraneous symptoms following burn injury is not fully understood. The integrity of the gut barrier is of critical importance as it harbors the largest bacterial reservoir in the body. Following burn injury, we observed a breakdown of the gut barrier resulting in increased gut leakiness and bacterial translocation. Under homeostatic conditions, heat shock proteins (HSPs) stabilize tight junction proteins. Particularly, HSP72 is …

Tcr Modifications To Enhance Expression, Chain Pairing, And Antigen Recognition For Adoptive T Cell Transfer, Kendra Foley

Master's Theses

T cell receptor (TCR) gene modified T cells for adoptive T cell transfer therapy have been shown to have clinical success in treating melanoma and other malignancies by redirecting the specificity of peripheral blood lymphocytes (PBL) to recognize tumor and/or viral associated antigens of choice. One of the challenges in using TCR gene modified T cells is the potential mispairing between endogenous and introduced alpha and beta TCR chains, allowing for unwanted off-target reactivity, autoimmunity, or impaired therapeutic efficacy. One approach to augment proper TCR chain pairing and to enhance T cell function involves the modification of the introduced TCR …

Role Of The Intestinal Microbiota In Gut Barrier Dysfunction Following Burn Injury, Zachary Earley

Master's Theses

Burn injury represents a major medical problem with half a million cases requiring medical attention and 4,000 deaths reported annually. Sepsis and multiple organ failure remain the leading causes of death following injury, and may be brought on by bacterial infections or toxins. The gastrointestinal tract contains approx. 100 trillion microbes; therefore, the indigenous commensal microbiota may play a role in leading to these complications or infections in burn patients. The overall objective of this project is to identify a potential mechanism whereby changes in gut bacteria may lead to intestinal inflammation or bacterial translocation--key factors which may lead to …

Characterizing The Mechanisms By Which Community Associated Methicillin-Resistant Staphylococcus Aureus Influences Keratinocyte Innate Immune Responses During Recurrent Infection, Ashley Lynn Larm

Master's Theses

Community associated–methicillin resistant Staphylococcus aureus (CA–MRSA) infection has become a major health concern. In human epidermal keratinocytes, S. aureus is mainly recognized through toll–like receptor 2 (TLR2) and its co–receptor, CD14. We hypothesize that CA–MRSA isolates cause recurrent infections by interrupting TLR2–mediated inflammation in keratinocytes. Recurrent CA–MRSA bacterial culture supernatant exposure to keratinocytes in vitro resulted in significant decreases in pro and anti–inflammatory cytokine and HMGB1 secretion from keratinocytes as assessed by ELISAs. Recurrent CA–MRSA live infection did not result in significant changes in cytokine or HMGB1 secretion, surface receptor expression, or NFκB activation post infection as assessed by ELISA …

The Effect Of Vitamin D On Human T Regulatory Cell Differentiation, Stephanie Anne Chapman

Master's Theses

Regulatory T cells (Tregs) are required for the induction and maintenance of immune homeostasis. Singh et al. demonstrated that depletion of Tregs in mice results in a loss of self-tolerance that manifests in the development of autoimmune diseases such as Inflammatory Bowel Disease (IBD). In humans, autoimmune diseases such as IBD, Multiple Sclerosis (MS), and Type 1 Diabetes are thought to occur due to a deficiency in the number or function of Tregs. The importance of Tregs in modulating the human immune system is perhaps best exemplified by IPEX (immune dysregulation, polyendocrinopathy, enteropathy, x-linked syndrome), a severe autoimmune disease characterized …

Evidence For Renewal And Reconstitution Of Marginal Zone Macrophages In Young And Aged Mice, Erika Bahamon

Master's Theses

Aging in humans and mice correlates with decline in immune health, affecting both innate and adaptive immunity. Response against blood-borne bacterial pathogens is compromised because of the deterioration of the marginal zones of the spleen and decrease in frequency of marginal zone macrophages (MZM). This thesis asked if low cell turnover is the cause for the decrease of MZM, using cell proliferation to indicate cell turnover in spleens of mice. First, evidence showed MZM proliferation occurred in spleens of young mice and was decreased in the MZM from aged mice. Second, transfer of young bone marrow into old mice replenished …

Characterization Of Inducible Regulatory T Cells: An Umbilical Cord Blood Model, Rebecca Anne Krier

Master's Theses

The immune system is a group of structures and processes that protect us from disease. To function properly it must recognize a wide variety of pathogens such as viruses and bacteria. T cells play a crucial role in an immune response; however, an overactive immune response can lead to autoimmune diseases, therefore it is important that the immune system has the ability to negatively regulate an immune response. In the periphery, regulatory T cells (CD4⁺CD25⁺Foxp3⁺) are involved in the maintenance of self-tolerance and immune homeostasis. Mechanisms involved in the induction of iTregs from naïve …

Selective Expansion Of B Cells By Intestinal Microbiota, Karina Ochoa

Master's Theses

In rabbits, antibody diversity and B cell expansion are generated in gut-associated lymphoid tissues (GALT), in an antigen- and T cell-independent mechanism, and require interaction with intestinal microbiota. I investigated, in vitro, the mechanism by which commensals drive GALT reactions. Bacteria were isolated from the GALT of rabbits and identified by 16sRNA sequencing. I found that the commensals can bind to Ig, independently of their specificity. In addition, a ~20kDa bacterial molecule was immunoprecipitated with recombinant Ig molecules. Stimulation of B cells with selected bacterial molecules induced the activation of B cells. Stimulation of B cells through TLR2 induced the …

Diffusion Barriers Of The Lateral Ventricular System, Anitha Saravanakumar

Master's Theses

Adult neurogenesis in mammalian brain has become a well-accepted phenomenon. The neural stem cells in the sub ventricular zone (SVZ) along the lateral wall of the lateral ventricle, the largest germinal center of adult neurogenesis, are maintained by the neural stem cell niche. One prominent feature of the niche is its close proximity to the cerebral spinal fluid (CSF). The role of micromolecules (such as ions, water and gases) present in the CSF and diffusing through the lateral ventricular wall and how the stem cell micro-environment is maintained is poorly understood. The cytoarchitecture of the lateral ventricular wall with a …

Urinary Antimicrobial Peptides And The Urinary Microbiota In A Uti-Susceptible Population Of Female Pelvic Floor Surgery Patients, Vanessa Nienhouse

Master's Theses

Urinary tract infections (UTI)s are a national priority. Women who undergo surgery for pelvic floor disorders such as pelvic organ prolapse (POP) or urinary incontinence (UI) are at increased risk for UTI, as 10-30% will contract a post-instrumentation UTI (postI-UTI) within six weeks after surgery. Currently, the factors that contribute to the high rate of postI-UTI are unknown, and there is currently no clinical assessment to identify at-risk patients. However, antimicrobial peptides (AMPs) and characteristics of the urinary microbiota have the potential to serve as biomarkers, identifying patients at UTI risk and facilitating clinical prevention studies.

While it was previously …

Binge Ethanol Leads To Decreased Macrophage Accumulation In Infected Cutaneous Wounds, Sara Hlavin

Master's Theses

Trauma patients who consumed alcohol prior to sustaining injuries have higher rates of morbidity and mortality than those with comparable injuries who did not drink. Additionally, those who drank had impaired wound healing and increased susceptibility to infection. Despite these clinical observations, few studies have explored the effect of ethanol on the innate immune cell function in a healing wound or how this may alter resolution of cutaneous infection. A murine model of ethanol and cutaneous wound infection was used to examine bacterial growth and recruitment of innate immune cells. Mice were given either ethanol (2.2 g/kg) or saline 30 …

Influence Of Detritus Levels And Organic Pollution On Interspecific Resource Competition, Oviposition Behavior, And Larval Survival Of Two Tire-Inhabiting Mosquito Species (Diptera: Culicidae), David Wayne Allgood

Master's Theses

Mosquitoes (Diptera: Culicidae) are vectors of disease in the adult stage, but understanding the factors affecting distributions of the immature stages is important to the understanding and control of adult populations. Discarded automobile tires comprise important larval mosquito habitats. The Asian tiger mosquito (Aedes albopictus) and the southern house mosquito (Culex quinquefasciatus) are two medically important species commonly found in tires, but factors affecting their larval distributions in tires have not been studied, nor have their interspecific interactions. I investigated the effects of chemicals associated with organic pollution on oviposition preferences and larval survival of both …

Role For Histone Deacetylases In Glucocorticoid Receptor Mediated Transpression Of Natural Killer Cell Activity, Kristin Bush

Master's Theses

During periods of psychosocial distress glucocorticoids (GCs) are known to reduce the lytic activity of natural killer cells (NKCA). Glucocorticoid treatment also reduces acetylation of histone residues; however, the glucocorticoid receptor (GR) lacks deacetylase activity. GR is known to interact with histone deacetylases (HDACs) and with corepressors that mediate gene transrepression. In this investigation, GC induced histone deacetylation was demonstrated to be due to GR recruitment of HDAC1 and the corepressor complex SMRT. These data show that reduced acetylation of immune functional genes associated with NKCA is likely due to histone deacetylation by HDAC1 and transrepression of those genes by …

Phenotypical And Functional Analysis Of Peripheral T Cells In Foxn1 Transgenic Mice: Effects Of Aging, Paulette Krishack

Master's Theses

The thymus is the primary organ for the development and production of TCRαβ naive T cells. However, with increasing age thymic involution occurs, causing a decline in the output of naïve T cells. The decline in naïve T cell production results in a contraction in the peripheral naïve and expansion of the memory T cell pools. Not only are the production and compositions of peripheral T cells altered with age, T cell functions such as T cell proliferation and production of cytokines required for cell proliferation are also declined. Currently, it is not known if restoring the decline in the …

Functional And Phenotypical Analysis Of The Effects Of Aging On B Cells And Their Bone Marrow Microenvironment, Nicole May Ziegler

Master's Theses

Aging impacts multiple organ systems, and specifically causes the immune system to lose its ability to efficiently fight off infections. Regarding immunity, aging research predominantly focuses on the adaptive immune system. B cells, which mediate the humoral arm of the adaptive immune system, develop throughout life in the bone marrow where microenvironmental `niches' are important. The bone marrow does not exactly `atrophy' with age; however, studies comparing young and old mice demonstrate an age-related change in the bone marrow B cell subpopulations.

The overall goal was to determine if femoral and sternum bone marrow have different plasma cell composition and …

Functional Effects Of Monoclonal Antibodies Directed Against The Tcr/Cd3 Complex Of Various T Cell Phenotypes, Mortimer T. Alzona

Master's Theses

No abstract provided.