Immunology and Infectious Disease Commons^™

Compensatory Mechanisms And T Cell Migration In Mouse Models Of Dopaminergic Loss, Kristi M. Anderson

Theses & Dissertations

Parkinson’s disease (PD) is the most common neurodegenerative movement disorder and second most common neurodegenerative disorder. PD is characterized by the selective loss of dopaminergic neurons and dopamine neurotransmitter within the substantia nigra and termini in the striatum. Progressive loss of dopaminergic neurons occurs over many years in PD, and by the time movement disorder symptoms manifest, up to 50-70% of dopaminergic neurons have been lost. Several aspects of PD pathology have been described in detail, but a better understanding of PD progression is needed to develop more efficient treatments.

Motor symptoms associated with PD do not manifest until significant …

Evidence For Using Immunosuppressive Treatments When Treating Idiopathic Non-Infectious Uveitis: A Systematic Review And Meta-Analysis, Hargurinder Singh

Electronic Thesis and Dissertation Repository

Idiopathic non-infectious uveitis is the spontaneous inflammation of the eye, which can lead to blindness if not treated correctly. Due to long-term side effects of corticosteroids, 4 classes of off-label immunosuppressive treatments are sometimes used (alkylating agents, inhibitors of T-lymphocyte signalling, antimetabolites and biological modifiers). We conducted a systematic review and meta-analysis to assess the effectiveness of different treatment classes on uveitis patients with similar characteristics. Results of the systematic review concurred with the conclusions from the meta-analysis, which found that all immunosuppressive treatments improved patient vision, with a statistically significant change in logMAR of -0.11 (95% CI of -0.152 …

Design And Testing Of Novel Anthrax Vaccines Utilizing A Tobacco Mosaic Virus Expression System, Ryan C. Mccomb

KGI Theses and Dissertations

Anthrax is a potentially fatal disease caused by the bacteria Bacillus anthracis. Infection and disease occur after spores gain entry into the body, germinate into vegetative bacteria, and produce toxin. Bacillus anthracis spores have been engineered as bioweapons and have been used repeatedly in warfare and terrorism to inflict casualties in military and civilian populations. Currently, only one vaccine has been approved for prevention of anthrax in the United States. This vaccine is an undefined product that is difficult to produce, requires a long vaccination schedule, and is reactogenic. Efforts to make an improved anthrax vaccine are being pursued. …

Health Assessment Of Two Reintroduced Populations Of American Martens (Martes Americana) In Michigan, Maria Catherine Spriggs

Doctoral Dissertations

The American marten (Martes americana) was extirpated from Michigan during the early-20th century due to loss of vast areas of mature conifer forest and unregulated trapping. The species was reintroduced into the Upper Peninsula (UP) and Northern Lower Peninsula (NLP) during the mid-20th century. While the American marten population in the UP has grown and is doing well, the population in the NLP has been less successful. The reasons for the limited success of the NLP population are unknown, but may include lack of suitable habitat, limited reproductive success, poor genetic diversity, disease, or negative environmental impacts. American …

Preventing Thymus Involution In K5.Cyclin D1 Transgenic Mice Sustains The Naïve T Cell Compartment With Age, Michelle L. Bolner

Dissertations & Theses (Open Access)

The thymus maintains T cell receptor (TCR) repertoire diversity through perpetual release of self-MHC restricted naive T cells. However, thymus involution during the aging process reduces naïve T cell output, leading to defective immune responsiveness to newly encountered antigens. We have found that early thymus involution precipitates the age-associated shift favoring memory T cell dominancy in young control mice. Furthermore, we have shown that age-related thymus involution is prevented in mice expressing a keratin 5 promoter-driven Cyclin D1 (K5.D1) transgene in thymic epithelial cells (TECs). Thymopoiesis occurs normally in K5.D1 transgenic thymi and sustains T cell output to prevent the …

Determining The Mechanisms Generating Soluble Il-15 Complexes, Scott Anthony

Dissertations & Theses (Open Access)

A diverse assortment of infectious pathogens and TLR agonists enhance the expression of Interleukin (IL)-15. Additionally, inducing lymphopenia enhances anti-tumor responses in an IL-15-dependent manner. Paradoxically, despite the limited expression of IL-15 during homeostasis, the role of IL-15 during the steady state is well-known, while its roles during inflammation and infections remain largely undefined. IL-15 uses a unique method of production and presentation to support the development and homeostasis of NK and CD8 T cells. IL-15 is produced with its high affinity IL-15Rα and this IL-15Rα/IL-15 complex is shuttled to the cell surface where it is presented in-trans or cleaved …

Role Of Stat3 In Human Nk Cell Functions, Prasad V. Phatarpekar

Dissertations & Theses (Open Access)

Natural Killer (NK) cells are cytotoxic lymphocytes, which play a critical role in the immune response against malignant cells and microbial infections. NK cells are equipped with activating receptors, which upon detecting ligands expressed on stressed cells induce cytolytic activity of NK cells. Stimulation of NK cell proliferation and priming of NK cytolytic capability are accomplished by cytokines, which mediate their signals mainly through JAK-STAT signaling pathway. Previously, we found that K562 cells genetically modified to express membrane bound IL-21 (mbIL-21), which predominantly activates STAT3, induce robust expansion and activation of human NK cells. Further investigations revealed role of STAT3 …

Plasmacytoid Dendritic Cell-Mediated Humoral Autoimmunity, Stephanie M. Dorta-Estremera Ph.D.

Dissertations & Theses (Open Access)

Humoral autoimmunity is characterized by the breakdown of B cell immune tolerance to self-antigens and consequent production of pathogenic autoantibodies. Plasmacytoid dendritic cells (pDCs), a potent type I interferon (IFN-I) producer, have been linked to the pathogenesis of systemic lupus erythematosus (SLE), a prototypic systemic humoral autoimmune disease. However, the cellular events that stimulate the development of humoral autoimmunity as a result of pDC activation have not been characterized. Moreover, the B cell subset(s) responsible for the generation of autoantibodies remains to be clearly identified.

The immunization of DNA-containing amyloids into non-autoimmune mice triggers the activation of pDCs and induction …

Examination Of The Chagas Disease Vector, Triatoma Gerstackeri, In The Lower Rio Grande Valley, Alfredo Flores

Theses and Dissertations

Chagas disease is caused by the protozoan parasite Trypanosoma cruzi, which is carried by an insect vector of the family Reduviidae, and of the subfamily Triatomina. The species Triatoma gerstaeckeri is identified as the primary vector of T. cruzi within the Rio Grande Valley. Species of Triatoma gerstaeckeri were trapped in La Sal del Rey National Refuge in 2012 and 2013.

Data indicates a seasonal dispersal pattern of activity for T. gerstaeckeri. Optimal time of capture was between 1-2 hours after sunset. Different methods were utilized to determine the best combination of lures. Results indicate that the UV-light alone is …

Chemoattractant Receptors Blt1 And Cxcr3 Regulate Anti-Tumor Immunity By Facilitating Cd8+ T Cell Migration To Tumors., Zinal S. Chheda

Electronic Theses and Dissertations

Presence of increased numbers of CD8⁺ T cells in the tumors correspond to better overall survival in the patients. Variety of immuno-therapies have shown considerable efficacy in the clinic, however, a multitude of patients remain unresponsive. Most of these immunotherapies rely on effector T cell responses in the tumor. A major obstacle in the success of these immunotherapies is poor recruitment of CD8⁺ T cells into tumors despite intact effector responses in the periphery. Therefore understanding the mechanisms that regulate CTL infiltration into tumors becomes essential. Previous studies in our laboratory suggested an important role for BLT1 in …

Defining The Molecular Networks Necessary For Thymus Fate And Organogenesis, Kaitlin A. Reeh

Dissertations & Theses (Open Access)

The thymus and parathyroid (PT) glands originate from endodermal progenitors in the bilateral third pharyngeal pouches (3^rd pps). By E11.5 during mouse development, cells committed to the thymus lineage express Foxn1 whereas PT-fated cells express Gcm2. While these transcription factors are required for organ-specific differentiation, the exact molecular mechanisms that specify endodermal progenitors to either the thymus or parathyroid lineage are not well defined. Tbx1 is initially expressed throughout the 3^rd pp endoderm, as it is required for segmentation of the pharyngeal apparatus, but is downregulated in the thymus-fated domain by E10.5. Despite the widely held notion …

Demography And Disease Of The Rare Shrub Buckleya Distichophylla (Santalaceae) In Northeastern Tennessee, William Seth Ratliff

Undergraduate Honors Theses

Piratebush (Buckleya distichophylla (Nutt.) Torr.) is a rare, hemiparasitic shrub with the only extant populations in western North Carolina, northeastern Tennessee, and southwestern Virginia. The preferred natural hosts of piratebush, Carolina and eastern hemlocks, have seen sharp declines over the last decade due to the invasive hemlock woolly adelgid. Virginia pine, another important host of piratebush, is also susceptible to disease, specifically Cronartium appalachianum, a rust fungus for which piratebush is the secondary host. This study described and analyzed current demographic parameters of three Tennessee piratebush populations. Additionally, spatial patterns of disease and demographic characters were analyzed. These …

Investigations Into The Cross-Infectivity Of Nematode Parasites Of Cattle And Sheep, Eva Marie Wray

Graduate Theses and Dissertations

The existence of anthelmintic resistance is not singular in parasite species, host species or geographic region. It has become a problem of worldly stature, especially when considering sheep nematodes. Recommendations have been modified from chemical-based control to multipart, managerial intervention. Compared with nematodes of cattle, the worldwide resistance of sheep nematodes to anthelmintic remedies is much more pronounced and urgent. As the resistance to essentially all anthelmintic classes approaches a cautionary level, the implementation of non-chemical controls has grown increasingly essential. Six-6 to 8 month old Holstein steer calves, six-5 month old Katahdin ram lambs and eight-5 month old Suffolk …

A Forward Genetic Screen Identifies Factors Associated With Fever Pathogenesis In Plasmodium Falciparum, Phaedra J. Thomas

USF Tampa Graduate Theses and Dissertations

Infectious diseases that spread from person-to-person and continent-to-continent are a cause for concern for any health entity. One such disease is malaria, a mosquito-borne infection instigated by the protozoan parasite, Plasmodium falciparum. Hundreds of millions of people are affected annually and it is responsible for nearly 1 million deaths. It is the most fatal species causing malaria and proliferates in human red blood cells with a life cycle occurring every 48 hours. At this time, the parasite’s late stage form or schizont bursts from the erythrocyte releasing immune-inducing particles and infective forms (merozoites) into the bloodstream. The merozoites go …

Characterization Of The Atsr/Atst Global Regulatory Pathway In Burkholderia Ceocepacia, Maryam Khodai-Kalaki

Electronic Thesis and Dissertation Repository

Phosphorylation cascades governed by two-component signal transduction systems provide key signalling mechanisms in bacteria, simple eukaryotes and higher plants, allowing them to translate signals into adaptive responses. These regulatory pathways consist of a transmembrane sensor protein that responds to an environmental cue leading to autophosphorylation, followed by the transfer of the phosphate to a cytoplasmic response regulator. Here, I study AtsR, a membrane-bound hybrid sensor kinase of Burkholderia cenocepacia, that negatively regulates quorum sensing related virulence factors such as biofilm, type 6-secretion and protease secretion. B. cenocepacia is a Gram-negative opportunistic pathogen which causes severe, chronic respiratory infections in …

Structure-Property Relationships At The Nano-Bio Interface: Engineering The Nanoparticle Surface For Immunomodulation, Daniel Fernando Moyano Marino

Doctoral Dissertations

Each year, a variety of novel nanomaterials are being developed with the objective of treating different diseases. However, since nanomaterials are foreign to the human body, one of the principal factors that limit their use is the encounter with the first line of defense from the body: the immune system. If this interaction is not taken into account, an undesired recognition takes place and the efficiency of nanoparticle based therapies is dramatically reduced. As such, understanding the rules that govern this recognition is of prime importance in the field of nanomedicine. Following this line of thoughts (the driving force), the …

Myeloid-Derived Suppressor Cells Contribute To The Subversion Of Innate Immunity During Staphylococcus Aureus Biofilm Infection, Cortney E. Heim

Theses & Dissertations

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature monocytes and granulocytes that are potent inhibitors of T cell activation. A role for MDSCs in bacterial infections has only recently emerged, and our laboratory was the first to demonstrate a functional role for MDSCs during Staphylococcus aureus (S. aureus) biofilm infection. Biofilm infections often lead to significant morbidity due to their recalcitrance to antibiotics and ability to subvert immune-mediated clearance by skewing the immune response toward an anti-inflammatory, pro-fibrotic phenotype. Therefore, we examined whether MDSCs could play a role in this process. CD11b⁺Gr-1⁺ MDSCs …

Role Of Macrophages In Muscle Transfection With Pdna/Pluronic Formulation, Vivek Mahajan

Theses & Dissertations

Non-ionic amphiphilic block copolymers of poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO), Pluronics, arranged in a tri-block structure PEO-PPO-PEO, have raised a considerable interest in skeletal muscle Gene Therapy. Previous studies have demonstrated that co-administration of Pluronics with naked plasmid DNA (pDNA) by direct i.m. injection enhanced transgene expression not only in muscle but also in distal lymphoid organs (spleen and lymph nodes) and this response was strain-dependent; not observed in athymic (BALB/c nu/nu) mouse; suggesting a role of immune cells in gene transfer to skeletal muscles. Therefore, we first evaluated the role of inflammation and inflammatory cells, on muscle …

Community-Acquired Methicillin-Resistant Staphylococcus Aureus (Ca-Mrsa) Usa300 Perturbs Acquisition Of Lysosomal Hydrolases And Requires Phagosomal Acidification For Survival In A Human Macrophage Cell Line, Zachary Ronald Tranchemontagne

All Theses And Dissertations

Community-acquired Methicillin-resistant Staphylococcus aureus (CA-MRSA) strain USA300 is a major cause of invasive drug-resistant skin and soft tissue infections in humans. Although S. aureus is a well-recognized extracellular pathogen, recent reports that USA300 survives inside host macrophages suggest that the intramacrophage environment may be a niche for persistent infection. Intramacrophage survival requires bacteria to avoid destruction in the phagosome; however, mechanisms by which USA300 evades phagosomal defenses are unclear. We examined the fate of the USA300-containing phagosome in human THP-1 macrophages by evaluating phagosomal acidification and maturation, and by testing the impact of phagosomal conditions on bacterial viability. Utilizing confocal …

Regulation Of Autoimmune Germinal Center Reaction By Tfh Cells And Application Of Tfr-Like Cells For The Treatment Of Autoimmune B Cell Responses, Young Uk Kim

Dissertations & Theses (Open Access)

Excessive follicular helper T (Tfh) cell responses to self-antigens are associated with antibody-mediated autoimmune diseases in humans including systemic lupus erythematosus (SLE). Numeral and functional aberrations of T regulatory T (Treg) cells are common in patients with autoimmune diseases. Although different types of immunosuppressive agents have been used clinically to treat antibody-mediated autoimmune diseases, they generally have side effects due to the lack of target-specificity. To minimalize the adverse effects, there is a need to develop target-specific therapeutics which specifically control auto-reactive B cell responses and auto-reactive Tfh cell responses. Recent studies unveiled that Foxp3⁺ Treg cells expressing CXCR5 …

Development And Evaluation Of Novel Vaccination Strategies For Campylobacter Control In Poultry, Xiang Liu

Masters Theses

Chicken is the primary natural host of Campylobacter, the leading bacterial cause of human enteritis in the US and other developed countries. Thus, mitigation of Campylobacter in chicken using innovative approaches, such as vaccination, will have a significant impact on food safety and public health. Our previous studies have demonstrated that the two outer membrane proteins, CmeC (the essential component of the CmeABC multi-drug efflux pump) and CfrA (a ferric enterobactin receptor), are feasible candidates for immune intervention against Campylobacter. DNA vaccine has appeared to offer various advantages for poultry, particularly when combined with in ovo vaccination. Chitosan-encapsulated …

Enhancement Of Hiv Persistence By Adipose Tissue, Jacob Couturier

Dissertations & Theses (Open Access)

A major challenge for HIV eradication is the persistence of cellular and anatomic viral reservoirs. The primary cellular reservoirs for HIV, memory CD4 T cells and macrophages, traffic into various tissues where most viral replication occurs, or in the case of virally-suppressed antiretroviral-treated patients, the virus becomes dormant and protected from drugs and immune responses. The major tissue reservoirs for HIV include lymphoid tissues such as lymph nodes, bone marrow, and gastrointestinal lymphoid tissues, but adipose tissues could potentially harbor HIV as well. Adipose tissues are ubiquitous connective tissues and major sites of infiltration and immune activity by T cells …

Aspirin Triggered Resolution Phase Interaction Product D1: A Novel Treatment For Hyperoxic Acute Lung Injury, Ruan Rollin Cox, Jr.

USF Tampa Graduate Theses and Dissertations

Acute Lung injury (ALI) and the more severe acute respiratory distress syndrome (ARDS) are respiratory maladies that present immense clinical challenges. ALI affects 200,000 individuals annually and features a 40% mortality rate. ALI can be initiated by both pathogenic and sterile insults originating locally in the lungs or systemically. While immense research has been poured into this disease in an effort to find a therapeutic strategy, the heterogeneously diffuse nature of the disease has not yielded a cure for the disease. Death from this disease is strongly attributed to reduced gas exchange from a severely compromised alveolar-capillary barrier. The only …

Bacterially-Based Immune Challenges And Trauma Elicit Terminal Investment In Male Aedes Aegypti, Molly K. Schumacher

Theses and Dissertations

Investment in life history traits such as immune function and reproduction is constrained by finite available resources. A cost-of-immunity trade-off may occur in response to infection when resources are diverted away from reproductive effort and into an immune response. Alternatively, an infected individual may enhance reproductive effort to maximize terminal reproductive success in response to the survival threat inherent to infection (terminal investment). We measured male Aedes aegypti reproductive behavior following inoculations with: living bacteria; killed bacteria as an immune elicitor; and a sham control. Mating competitiveness relative to naïve males was also determined through a binary mate choice experiment …

Comparison Of Different Modulators That Affect Macrophage Activation In Vitro, Alda Alexa Díaz Pérez

Graduate Theses and Dissertations

Inflammation is known as a mechanism to regulate and control infections as well as promote tissue repair. Macrophages (Mф) are known to be a major cell type in the initiation, sustainability and resolution of inflammation. Moreover, Mф are essential for the remodeling process that is also known as the wound healing response. The objective of this research was to compare five modulators (acetylsalicylic acid (ASA), dexamethasone (DEX), prostaglandin E2 (PGE2), iloprost, and resolvin D1 (RvD1) for their anti-inflammatory effects on macrophages in vitro. Then, Mф phenotype in terms of gene expression and secreted cytokine response was determined. Our study compared …

A Study Of A Simulated Infectious Disease On Healthcare Workers' Reaction, Knowledge, Attitudes, And Performance Towards Hand Hygiene, Lydia Wigglesworth-Ballard

Health Services Research Dissertations

Problem Statement. The high rate of healthcare worker-patient contact provides many opportunities for exposure to pathogens, which creates challenges in assessing healthcare workers' success at preventing healthcare associated infections caused by these dangerous pathogens.

Methods. This study explored the effects of a simulated infectious disease on healthcare workers' hand hygiene knowledge, attitudes, performance, and reactions using Kirkpatrick's Four levels of Evaluation. The study utilized a mixed method pre-test – 2 post-test design. The dependent variables were hand hygiene knowledge, attitudes toward hand hygiene guidelines, hand hygiene performance, and reaction to the overall experience. Data was collected three times over a …

Expression, Localization, And Kinetic Characterization Of The Phospholipid Biosynthesis Enzyme Ctp: Phosphocholine Cytidylyltransferase From The Protozoan Parasite Leishmania Major, Justin Daniel Theodore Lange

Theses and Dissertations

The eukaryotic parasite Leishmania is the causative agent of the disease leishmaniasis. L. major is the most common of 21 species that causes visceral leishmaniasis in humans, and 30 that cause the same disease in other mammals. Visceral leishmaniasis causes fever, weight loss, and over a short amount of time, multiple organ failure, and has a 100% mortality rate within 2 years. This makes it the second largest parasitic killer in the world behind malaria. Over 90% of the worldâ??s cases of visceral leishmaniasis have been reported in underdeveloped countries of India, Bangladesh, Nepal, Sudan, Ethiopia and Brazil, with 500,000 …

Granulocyte Colony-Stimulating Factor: Its Role In Gut-Homing Macrophage Generation And Colitis, And Production By Probiotics, Shahab Meshkibaf

Electronic Thesis and Dissertation Repository

The pleiotropic cytokine granulocyte-colony stimulatory factor (G-CSF) is mainly required for the generation of neutrophils, but its role in macrophage generation has also been reported. In addition, G-CSF is effective for the down-regulation of inflammatory cytokines and ameliorating gut disorders, such as colitis. However, the G-CSF function in macrophage generation and gut immunity remains unclear. The first focus of this thesis was to assess the role of G-CSF in macrophage generation and its contribution to gut immunity. G-CSF was found to promote the generation of Gr-1high/F4/80+ macrophages in macrophage (M)-CSF-treated bone marrow cells, most likely through suppressing cell death. Gr-1high …

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 …

Lyme Disease In The Northeast: Altered Ecosystems And Public Health Impacts, Elisa L. Russo

Student Theses 2015-Present

Lyme disease has spread rapidly throughout the United States since its original discovery in 1975. An increasing threat to public health, this common vector-borne disease is transferred to a human after receiving a bite from an infected blacklegged tick (Ixodes scapularis). Humans have contributed to the massive influx of tick populations and Lyme disease cases through the introduction of invasive flora and fauna, overhunting of apex predators, and altering areas of land for urbanization. Quantitative data from the CDC and USDA on Lyme disease cases and white-tailed deer populations in the United States demonstrates the impact of human …