Immunology and Infectious Disease Commons^™

Study Of Rickettsia Parkeri Colonization And Proliferation In The Tick Host Amblyomma Maculatum (Acari: Ixodidae), Khemraj Budachetri

Dissertations

Amblyomma maculatum (Gulf coast tick) ticks are prevalent across the Atlantic to Gulf Coast region of United States. These ticks are recognized vectors of Rickettsia parkeri, a spotted fever group of Rickettsia (SFGR) known to cause American boutonneuse fever associated with fever and eschar rashes localized to the site of bites. We hypothesized that Rickettsia parkeri colonization and proliferation in the tick vector involve pathogen-symbiont dynamics and tick-pathogen interactions, which influence rickettsial transmission to the victims after tick bites. The rickettsial infection is maintained across the tick life cycle for many generations due to transovarial and transstadial transmission of …

Role Of The Interleukin-22 And Stat3 Signaling Pathway In Gut Barrier Maintenance Following Intoxication And Burn Injury, Adam M. Hammer

Dissertations

More than half of patients admitted to burn centers for treatment have measurable alcohol levels in their blood. Intoxication that precedes a traumatic burn injury leads to worsened patient outcomes, including higher rates of infection and sepsis. The intestines harbor the largest concentration of bacteria in the human host. Any disruption of the intestinal barrier as a result of intoxication and burn injury could contribute to infection and/or sepsis from gut-derived microbes. Previous work has demonstrated that the intestinal barrier becomes leaky, and that administration of interleukin-22 (IL-22) significantly reduces gut barrier leakiness following alcohol and burn injury. However, the …

A Microbiomic Approach To The Characterization Of The Impacts And Influences Of Viral, Bacterial, And Harmful Algal Bloom Toxins On The Bottlenose Dolphin, Corey David Russo

Dissertations

As apex predators that display high site fidelity Tursiops truncatus (bottlenose dolphin) are indicators of marine ecosystem health. Bottlenose dolphins, additionally, display pathogenesis and immune response similar to that of humans. Humans and coastal bottlenose dolphins, in particular, are constantly exposed to the same industrial, agricultural and domestic toxins and pathogens, contaminants and pollutants. Thus, studies on the bottlenose dolphin are also valuable in bridging the gap between ocean and human health. Bottlenose dolphins are susceptible to viral bacterial and toxin infection. Infection in the bottlenose dolphin manifests itself in the form of mass stranding events, unusual mortality events, chronic …

Patterns Of Olfactory Neurogenesis And Immune Response In Adult Zebrafish Following Damage Of The Olfactory Bulb, Darcy M. Trimpe

Dissertations

The adult zebrafish olfactory system, with its persistent neuronal turnover and abundant regenerative capacity, is an excellent model system for studies of adult brain plasticity. Reversible deafferentation, achieved by repeated intranasal irrigation with detergent, reduces bulbar innervation and affects bulb structure and function, while cessation of treatment permits reinnervation and recovery of bulb volume. Alterations in cell genesis may account for this phenomenon. This study focuses on adult neurogenesis in the zebrafish olfactory system following reversible deafferentation and direct olfactory bulb injury.

Potential alterations in cell proliferation, differentiation, migration, and survival in the olfactory bulb following single and repeated intranasal …

Monocyte-Induced Regulatory T Cell Differentiation, Jessica Genevieve Lee

Dissertations

Immediately after birth, thousands of foreign antigens challenge the newborn immune system. Many of the invaders are harmless, such as food, pollen, and beneficial bacteria. Newborns have a tolerant immune system that keeps them from developing inflammation or allergies to these new antigens. In utero, this immunoregulatory tendency is important for establishing tolerance to self and maternal antigens. Multiple processes contribute to fetal tolerance, including clonal deletion, anergy, changes in antigen presenting cells (APCs), and the generation of regulatory T cells (Tregs). However, the mechanism(s) of fetal Treg differentiation and the specific APCs required are unknown.

Our lab has previously …

Mechanism By Which Commensal Bacteria Limit Inflammation, Mallory Paynich

Dissertations

Trillions of bacteria live within the gastrointestinal tract and are critical for maintaining intestinal homeostasis; however, the mechanisms utilized by specific bacterial molecules to contribute to homeostasis are not well understood. We utilize a mouse model in which a single oral dose of the probiotic, Bacillus subtilis, protects mice from acute colitis induced by the enteric pathogen Citrobacter rodentium. Our goal is to elucidate the mechanism by which B. subtilis prevents inflammation.

We identified exopolysaccharides (EPS) to be the active molecule of B. subtilis, and a single dose of EPS protects mice from disease. EPS binds F4/80+CD11b+ peritoneal macrophages, and …

Inhibition Of B Lymphopoiesis By Adipocytes And Myeloid-Derived Suppressor Cells, Domenick Kennedy

Dissertations

B lymphopoiesis declines with age in humans, mice, and rabbits. Impaired B lymphopoiesis correlates with increased fat in the bone marrow (BM), suggesting that adipocytes negatively regulate this process. In fact, adipocyte factors were found to inhibit B cell development in BM cultures.

Our goal was to understand the mechanism by which adipocytes inhibit B cell development. Through culturing mouse BM cells on OP9 stromal cells in the presence of adipocyte-conditioned medium (ACM), we found that adipocytes promote the accumulation of CD11b+Gr1+ myeloid-derived suppressor cells (MDSCs). These cells were not simply bystanders, as we report for the first time that …

Antiviral Responses In Mouse Embryonic Stem Cells: Differential Development Of Cellular Mechanisms In Type I Interferon Production And Response, Ruoxing Wang

Dissertations

Embryonic stem cells (ESCs) have been recognized as a promising cell source for regenerative medicine. Intensive research over the past decade has led to the possibility that ESC-derived cells will be used for the treatment of human diseases. However, increasing evidence indicates that ESC-derived cells generated by the current differentiation methods are not fully functional. It is recently recognized that ESC-derived cells lack innate immunity to a wide range of infectious agents and inflammatory cytokines. When used in patients, ESC-derived cells would be placed in wounded sites that are exposed to various pathogens and inflammatory cytokines; therefore, their viability and …

Identification And Analysis Of Omentum Derived Suppressor Cells In Regards To Th17 Inhibition, Nick Huang

Dissertations

Omentum has been harnessed by surgeons for hundreds of years, providing an ideal environment for graft healing and acceptance. However, little is known about the cellular mechanisms that promote the tolergenic environment of the omentum. We examined the cellular composition and role of activated omentum in regards to T-cell immunomodulation. We then tested activated omentum as a cellular therapy in a mouse allogenic lung transplantation model.

Our findings demonstrated activated omentum is mostly comprised of non-hematopoietic cells resembling mesenchymal stem-like cells (MSCs) and myeloid derived suppressor cells (MDSCs). Activated omentum exhibited anti-inflammatory properties through suppression of Th1 and Th17, while …

Role Of Msa In Immune Evasion, Persistence, And Protease Regulation In The Human Pathogenic Strains Of Staphylococcus Aureus, Maria Deepa Basco

Dissertations

Opportunistic pathogens like Staphylococcus aureus on entering the host can stay colonized at the foci of infection or evade the immune system to disseminate to other sites. In this study we investigated the regulatory influence of the modulator of sarA (msa) on immune evasion and host persistence, employing the hospital-acquired strain S. aureus UAMS-1 and community-acquired strain S. aureus USA300 LAC. In the murine sepsis model, mutation of the msa gene in LAC showed no change in dissemination of infection; however, in UAMS-1 a decrease in microbial load was observed in the lungs. Differential regulation by the msa gene was …

Particulates Initiate Immune Response Via Inducing Oxidative Stress-Mediated Nlrp3 Inflammasome Activation, Zhenyu Zhong

Dissertations

Liposomes are lipid particles formed by self-aggregated phospholipids. They are clinically used both as delivery vectors and immune adjuvants to treat many human infectious and cancerous diseases. However, how liposomes interact with host immune system remains poorly understood. Particularly, little is known about whether an innate immune receptor exists to sense liposomes. I hypothesize that liposomes activate NLRP3 inflammasome in macrophages, which results in the release of interleukin 1β (IL-1β), a proinflammatory cytokine that plays a key role in innate and adaptive immune responses.

To test my hypothesis, I determined the ability of inducing IL-1β secretion from macrophages by differentially …

Psychosocial Distress Mediates Immune Dysregulation Through Alterations In Global Epigenetic Patterns And Chromatin Remodeling Proteins, Karen Krukowski

Dissertations

Psychosocial distress, characterized by increased perceived stress, anxiety and mood disturbance, is a common response of women to a diagnosis of breast cancer (Northouse, 1992; Pettingale et al., 1988; Stark and House, 2000; Witek-Janusek et al., 2007). This psychosocial distress leads to activation of the hypothalamic-pituitary-adrenocortical (HPA) axis and increased circulating glucocorticoids (GCs) (Chrousos, 2000; Chrousos and Gold, 1992; Schoneveld and Cidlowski, 2007). Increased psychosocial distress and increased HPA activation can lead to immune dysregulation consisting of reduced natural killer (NK) cell activity (NKCA) (Biondi, 2001; Kiecolt-Glaser et al., 1987; Kiecolt-Glaser et al., 2002; Witek-Janusek et al., 2008; Witek-Janusek et …

Characterization Of Chronic Glucocorticoid Exposure On Natural Killer Cell Function: A Model For Stress Induced Alterations On The Epigenetic Landscape, Justin Lee Eddy

Dissertations

Psychological stress can impact immune function through altered glucocorticoid production. Natural killer (NK) cells and their effector functions are particularly susceptible to both psychological stress as well as exogenous glucocorticoids. The purpose of this study was to assess the impact of chronic glucocorticoid (GC) exposure on NK cells to investigate the immune dysregulation associated with periods of psychological stress.

Chronic in vitro treatment of the NK92 cell line produced a dichotomous NK phenotype with enhanced proinflammatory cytokine production yet reduced NK cell lytic activity (NKCA). This dichotomy was at the individual cell level where mRNA and protein levels for proinflammatory …

Ex Vivo Induction Of Human Regulatory T Cells, Kathleen Elizabeth Jaeger

Dissertations

Regulatory T cells (Tregs) are indispensable in the human immune system in the maintenance of self-tolerance and immune homeostasis. The dysregulation of Treg number and/or function plays a critical role in the pathogenesis of cancer, allergy and human autoimmune pathologies such as multiple sclerosis, psoriasis, rheumatoid arthritis and diabetes. The primary aim of this research was to determine the molecular mechanisms and cellular interactions which promote human Treg induction. From umbilical cord blood (UCB) samples, we found that antigen receptor stimulation of UCB T cells via a CD14+ monocyte population leads to a predominant induction of Tregs.

Further studies identified …

Defining A Role For Inducible Heat Shock Protein 70 (Hsp70i) In Mediating Autoimmune Vitiligo, Jeffrey Alan Mosenson

Dissertations

Vitiligo is an autoimmune disease characterized by destruction of melanocytes, leaving 0.5% of the population with progressive depigmentation. Current treatments offer limited efficacy. Observations that heat shock proteins (HSPs) can serve as adjuvants in antitumor vaccines first suggested to us a link between HSPs and stress-induced vitiligo. Such proteins are marvelously well conserved throughout evolution, which has placed them in the spotlight for helping to understand the intriguing relationship between infection and immunity. Intracellularly, inducible heat shock protein 70 (HSP70i) is upregulated by stress and helps protect cells from undergoing apoptosis. In times of stress, melanocytes will secrete antigen bound …

Genetic Variation In Potentially Virulent Vibrio Parahaemolyticus From The Northern Gulf Of Mexico, Nicholas Felix Noriea Iii

Dissertations

Vibrio parahaemolyticus (V_p) is a gram-negative bacterium found naturally in marine and estuarine environments. V_p is found in oysters including those which are later consumed by the public. Sub-populations of potentially virulent Vp contain specific virulence factors and are relevant human pathogens capable of causing gastroenteritis, wound infection, and death. The tdh and trh genes, both encoding hemolysins, have been correlated with the majority of clinical V_p isolates but have not been shown to be the definitive virulence factors.

A total of 146 V_p isolates from the northern Gulf of Mexico were collected and probed …

Clam (Corbicula Fluminea) As A Potential Sentinel Of Human Norovirus Contamination In Freshwater, Xunyan Ye

Dissertations

The purpose of this study was to evaluate and validate the use of the clam Corbicula fluminea as a sentinel of human noroviruses (HuNoV) contamination in freshwater. The first specific aim was to develop a new method to extract HuNoV RNA from contaminated bivalves (e.g. oysters, clams) that would be much faster than existing methods. The procedure developed includes an initial total RNA extraction using TRI Reagent, followed by HuNoV RNA concentration and purification using biotinylated probe-capture technology. HuNoV RNA is finally detected by real-time RT-PCR. Using bivalve homogenates spiked with HuNoV, 100 PCR detection units of the virus was …

Cell Biology Of Foxp3+ Regulatory T Cells, Mariko Takami

Dissertations

T cells play a central role in the immune response to fight against pathogens and orchestrate other immune cells. An overreactive immune response can lead to autoimmune diseases, therefore the immune system must possess negative regulation mechanisms. In the periphery, naturally arising regulatory T cells (nTregs) negatively regulate immune responses and play an important role in maintaining immune homeostasis. When antigens are present, conventional CD4+ T cells recognize their cognate antigen and proliferate. After pathogen clearance, expanded effector T cells eventually decline in number due to activation induced cell death (AICD) to terminate immune response. However, it is not understood …

Positive Emotions And Immune Respose To Influenza In Medically Stable Older Adults, Maryann J. Gierloff

Dissertations

Influenza results in substantial human suffering and health care costs. Evidence from psychoneuroimmunology suggests that emotions influence the immune system and may alter susceptibility to infectious diseases, like influenza. The purpose of this investigation was to evaluate the influence of psychological factors, health behaviors, circulating levels of proinflammatory cytokines and the development of influenza-like illness in older adults. Medically stable participants, 55 years of age and over, were enrolled from the general community and an elderly community. Psychological factors (emotions and perceived stress), health behaviors (sleep and physical activity) and plasma cytokine levels (IL-6 and IL-1B) were evaluated with respect …

Promoting Thymopoiesis With Age: Potential Role Of The Transcription Factor Foxn1, Erin Christine Zook

Dissertations

It is known that the elderly are more susceptible to illnesses and infections and respond poorly to immunization. A contributing factor to a decrease in the immune response in the elderly is the decline in the production of naïve T cell by the thymus. In the thymus, the notch receptor expressed on early T cell progenitors (ETP) binds to its ligand expressed on thymic epithelial cells (TEC), signaling ETP to develop through a series of developmental stages before maturing into naive T cells. Because ETP are non-self renewing, the thymus relies on the bone marrow (BM) for a continuous supply …

Mechanism For Pre-B Cell Loss In Mutant Ali/Ali Rabbits, Gregory Robert Robbins

Dissertations

Pre-B cell receptor (pre-BCR) signaling is a critical checkpoint in B cell development in which B-lineage cells expressing functional μ-chains undergo selective expansion. My dissertation work used a rabbit model system to study how VH structure affects the early stages of B cell development in the bone marrow (BM). Developing B cells in mutant ali/ali rabbits predominantly utilize VH4 during VDJ gene rearrangement. However, most of the VH4-utilizing B cells encounter a severe block early in B cell development. In contrast, wildtype rabbit B cells predominantly rearrange VH1, a gene >90% identical to VH4, and develop normally. We hypothesized that …

Alternations In The Splenic Marginal Zone With Age, Shirin Z. Birjandi

Dissertations

Splenic marginal zones are architecturally organized to generate a rapid response against blood- borne antigens entering the spleen. The marginal zone is a distinct anatomical micro-environment whose main components include the marginal zone macrophages, the marginal zone B cells, the marginal zone sinus, and the metallophilic macrophages. Marginal zone macrophages, in partnership with marginal zone B cells, are particularly important in host defense against T-independent pathogens and are crucial for the prevention of diseases such as Streptococcus pneumonia. It has been widely reported that with the advancement of age there is a higher rate of mortality as a result of …

Regulation Of Biofilm And Antibiotic-Resistance By The Modulator Of Sara (Msa) In Staphylococcus Aureus, Antony Schwartz

Dissertations

Staphylococcus aureus is an important human pathogen that is the causative agent of life-threatening diseases such as endocarditis and osteomyelitis. The ability of S. aureus to thrive as a successful pathogen can be partially attributed to its ability to form biofilm. Biofilm is an extracellular polysaccharide, protein, and DNA-based slime layer that protects the bacterial community. The global regulator sarA is essential for biofilm formation. Since the modulator of sarA (msa) gene regulates several virulence factors and is required for the full expression of sarA, the capacity of the msa mutant to form a biofilm was examined. The mutation of …

Aging Effects On Acute Lung Inflammation After Burn Injury, Vanessa Nomellini

Dissertations

The risk of complications and death after a moderate sized burn injury is significantly higher in persons over the age of 65, while almost non-existant in young, healthy individuals. The studies outlined below use a murine model to determine the mechanisms behind the development of pulmonary complications that frequently occur in aged individuals following burn injury. We hypothesized that, since aged mice maintain an elevated proinflammatory state prior to injury, they are at an even greater risk of pulmonary inflammation than young mice given a comparable sized wound. We found that neutrophils continue to accumulate in the lungs of aged …

Phospholipase D Signaling In T Cells, Uma Chandrasekaran

Dissertations

Antigen stimulation of T lymphocytes induces the activation of phospholipase D (PLD) signaling. Phospholipase D (PLD) is a phosphodiesterase that catalyzes the conversion of phosphatidyl choline (PC) to phosphatidic acid (PA). PA is an important lipid second messenger and is known to mediate a variety of cellular functions. However, the specific role of PA in T lymphocytes has not been established. Previous studies indicated differential requirement for TCR induced PLD signaling in regulatory and non-regulatory T cells. Inhibition of TCR induced PLD signal preferentially suppressed the growth of non-regulatory T cells while allowing the proliferation of regulatory T cells in …

B Lymphocyte Development In Galt, Venkata Arunachalam Yeramilli

Dissertations

In rabbits, the primary antibody repertoire is generated in the gut-associated lymphoid tissues (GALT), where bone marrow (BM)-derived B cells undergo a proliferative expansion and somatically diversify the immunoglobulin genes. Unlike in other species, B lymphopoiesis in rabbit arrests a few months after birth, and it is unclear how the peripheral B cell compartment is maintained when there is no influx of newly-made B cells from the BM.

For my dissertation, I investigated how B cells develop in the GALT of rabbits, and how they are maintained in adults after the arrest of lymphopoiesis. To identify cellular signals that promote …

Ethanol Impairs Mechanisms Of Macrophage Phagocytosis And Cytokine Production, John Karavitis

Dissertations

Extensive evidence indicates that alcohol (ethanol) consumption affects human health by altering normal physiological functions of the immune system. This study investigated the effect of a single in vivo exposure of macrophages to clinically relevant levels of ethanol (1.2 and 2.2 g/kg). Following 3 hour exposure, both doses of ethanol decreased ex vivo TNFα production by splenic and alveolar macrophages (AMs). Interestingly, the higher dose of ethanol resulted in sustained suppression of LPS-induced TNFα production at 3 and 6 hours post ethanol administration, as well as decreased IL-6 and IL-12 production after 6 hours, compared control treated groups. LPS or …

The Role Of Msa In The Global Regulation Of Virulence In Staphylococcus Aureus, Vijayaraj Nagarajan

Dissertations

Staphylococcus aureus is an important pathogen causing life threatening diseases in humans. Previously we showed that msa modulates the activity of sarA (Staphylococcal accessory regulator), which is one of a major global regulator of virulence in S. aureus. The objective of this study is to characterize the role of msa (Modulator of SarA) in the global regulation of virulence in S. aureus. Structure and function predictions were done using several computational tools and approaches to understand the nature of msa. A novel S. aureus microarray meta-database (SAMMD) was designed and developed to compare and contrast other transcriptomes with msa transcriptome. …

Identifying The Processed Products Of The Polymerase Polyprotein Of Coronavirus, Hong-Qiang Gao

Dissertations

No abstract provided.