Medicine and Health Sciences Commons^™

An Investigation Of The Levels Of Pro-Inflammation Cytokines In The Brain Of Autoimmune Lewis Rats, Han Yang

Theses & Dissertations

Rheumatoid arthritis (RA) is a chronic inflammatory joint disease, which can cause cartilage and bone damage, as well as disability. A reported symptom of RA includes tissue inflammation disease and cognitive dysfunction. This study aimed to compare the concentration of selected cytokines in the cerebral cortex, hippocampus, hypothalamus, amygdala, and cerebellum of Lewis rats. Age and sex-matched Lewis rats were separated into two groups: control and adjuvant-induced RA. Twenty-eight days after the adjuvant injection, groups were sacrificed and brains dissected using the stereotaxic atlas of Paximos and Watson as a guide. Pro-inflammatory cytokines IL-1β, IL-6, and IL-23, plus the anti-inflammatory …

Mechanism Of Candida Albicans Biofilm And Virulence Inhibition By A Bacterial Secreted Factor, Carrie Graham

Dissertations & Theses (Open Access)

The human microbiome is a diverse polymicrobial population comprised of both fungi and bacteria. Perturbations of the normal microbiome can have a profound impact on health, including the development of infections. Exploitation of these polymicrobial interactions has the potential to provide novel treatment and prevention strategies for infectious diseases. Enterococcus faecalis, a Gram-positive bacterium, and Candida albicans, a polymorphic fungus, occupy overlapping niches as ubiquitous constituents of the gastrointestinal and oral microbiome. Both species are also amongst the most important and problematic, opportunistic nosocomial pathogens and are often co-isolated during infection. Surprisingly, these two species antagonize each other’s …

A License To Kill: Understanding Natural Killer Cell Licensing To Fight Cancer, Jolie Schafer

Dissertations & Theses (Open Access)

Natural killer (NK) cell education is an essential developmental process for NK cell effector function, that renders some NK cells “licensed” and others “unlicensed” (with heightened or lowered effector function potential, respectively) against tumor and targets lacking self-molecules. However, the underlying mechanisms responsible for the heightened effector responses of licensed cells remain unknown. Using NK cells derived from humans and expanded ex vivo we performed high-throughput protein expression analysis, and identified multiple proteins that are differentially regulated in licensed and unlicensed human NK cells before and after inhibition by killer-cell immunoglobulin-like receptors (KIRs) and activation by the NKp46 natural cytotoxicity …

Improving Hpv Vaccination Series Initiation Rates And Compliance Among Indigent Women In South Texas, Ages 19-26, Through Provider Recommendation And Additional Clinic Funding: A Quality Improvement Project, Lacey Cudd

Doctor of Nursing Practice

The purpose of this quality improvement project was to increase human papillomavirus vaccination series initiation rates among indigent women, ages 19-26, at a clinic in South Texas. The human papillomavirus is a sexually transmitted infection that has been associated with multiple types of cancers. Each year, approximately 6.2 million cases of the human papillomavirus infection are diagnosed; as many as 75% of all new infections occur among females 18-26 years of age. The human papillomavirus vaccination has a high efficacy in regards to cancer prevention, preventing as many as 76% of cancers with only one dose. The project included educating …

Dynamic Assessment Of Nk Cell Interactions With Pediatric Tumor Cells To Predict Response To Immunotherapy, Arianexys Aquino Lopez

Dissertations & Theses (Open Access)

Due to Natural Killer (NK) cells’ capacity to target tumor cells without prior sensitization, adoptive NK cell therapy represents a promising immunotherapy approach for pediatric cancer patients. Our laboratory has developed an NK cell expansion protocol that generates large quantities of NK cells for therapeutic infusion. Given that NK cells are heterogeneous, with variable receptor expression and potential to target tumor cells, the purpose of my study was to determine whether subpopulations of NK cells with enhanced anti-tumor potential could be identified for increased potency of the NK cell infusion product. In addition, we previously showed that our expanded NK …

Type Ix Secretion System : Characterization Of An Effector Protein And An Insight Into The Role Of C-Terminal Domain Dimeration In Outer Membrane Translocation., Lahari Koneru

Electronic Theses and Dissertations

Porphyromonas gingivalis and Tannerella forsythia are two of the primary pathogens that are associated in the etiology and progression of chronic periodontitis. In T. forsythia, KLIKK proteases are the recently identified group of proteolytic enzymes that are secreted through Type IX secretion system (T9SS). Among, these KLIKK proteases a synergistic relationship was observed between karilysin and mirolysin in invading the host complement system for the survival of the bacteria. Since, karilysin has been already characterized, in this study we propose to study about mirolysin through structural, biochemical and biological characterization. The obtained results from the experiments has shown the …

Memory Potential, Molecular Characterization, And Translational Applications Of The Novel Theo/Tceo T Cell Phenotype, Todd Bartkowiak, Todd Bartkowiak

Dissertations & Theses (Open Access)

T cells comprise a substantial arm of the immune system and are exquisitely adapted to combat pathogens and tumors. The inflammatory environment largely dictates the nature of T cell response. A hallmark of T cell-mediated immunity is formation of immunological memory; the ability to respond more potently to re-encounter with pathogens. The immune system is also capable of recognizing tumors as foreign, much like viral or bacterial pathogens. Tumors have evolved, though, to generate an immunosuppressive environment to avoid destruction. The field of immunotherapy seeks to overcome immune suppression, in part by targeting T cell co-receptors on the cell surface …

Membrane Bound Il21 Promotes Natural Killer Cell Expansion Through Mir 124-3p Mediated Regulation, Anitha Somanchi

Dissertations & Theses (Open Access)

Natural Killer (NK) cells are cells of the innate immune system that act as first line of defense against viral infections and participate in tumor immune surveillance. NK cells do not cause graft versus host disease (GvHD), or require prior antigen exposure to exert anti-tumor activity, hence are an attractive choice for immunotherapy applications. Owing to small numbers of NK cells in peripheral blood (1-32%, with a 6% median), ex vivo expansion of NK cells is critical for NK cell adoptive immunotherapy, various expansion platforms have been explored over the decades. We developed a robust platform for ex vivo expansion …

Cost-Effectiveness Analysis Of Targeted Herpes Zoster Vaccination In Adults 50-59 At Increased Cardiovascular Risk, Kathleen M. Glassner

USF Tampa Graduate Theses and Dissertations

Background: Over the last twenty years the incidence of herpes zoster (HZ) infection, also known as shingles, has been increasing among adults for unknown reasons. The economic burden of HZ is currently estimated at over $1 billion per year in the United States (U.S.) and is expected to increase as the susceptible adult population ages. HZ is caused by a re-activation of the varicella zoster virus (VZV), chicken pox, and more than 95% of adults living today carry the virus with a lifetime risk of 1 in 3 for developing HZ. In 2006 the FDA approved a vaccine for the …

Evaluation Of A Microsphere-Based Immunoassay (Mia) In Measuring Diagnostic And Prognostic Markers Of Dengue Virus Infection, Jason H. Ambrose

USF Tampa Graduate Theses and Dissertations

Infections with dengue viruses (DENV) constitute both a global problem as well as locally in Florida. DENV comprise four distinct serotypes of single-stranded RNA viruses and belong to the family Flaviviridae. DENV are among the most medically important arboviruses in the world and cases may currently exceed 400 million per annum. Additionally, dengue established its first recorded endemic transmission cycle in the state of Florida in over a half century, first within the Florida Keys during 2009-10 followed by an unrelated outbreak in Martin County in 2013. The clinical profile of DENV infections ranges from a mild febrile illness …

Synthesis, In Vitro Characterization And Applications Of Novel 8-Aminoquinoline Fluorescent Probes, Adonis Mcqueen

USF Tampa Graduate Theses and Dissertations

Malaria is a parasitic disease that is caused by the plasmodium parasite. Plasmodium infection has affected man for thousands of years. With advances in drug discovery over the past century, malaria has evolved to possess resistance to most mainline therapeutics. This war of drug discovery vs plasmodium evolution continues to be fought to this very day, with attempts to eradicate malaria worldwide. Frontline treatments such as chloroquine, artemisinin, and atovaquone/proguanil have all seen parasitic resistance in strains of P. vivax as well as P. falciparum. While plasmodium possesses resistance to most classes of anti-malarials, the 8-aminoquinoline (8-AQ) class has …

Effects Of Carboxylated Nanodiamonds On Macrophages During And After Differentiation, Maisoun E. Bani Hani

Biological Sciences Theses & Dissertations

Nanodiamonds (ND) are a carbon-based nanomaterial that are increasingly being proposed for developing novel imaging techniques, as carriers of biomolecules and therapeutic drugs, as coatings for implants, and for other biomedical applications. The exceptional chemical, mechanical, and optical properties of ND make this material suitable in a wide range of fields. The application of ND in the biomedical field is attractive but requires more in-depth investigation into the safety of ND and its interactions with different cells and systems. The effects of ND on the immune system are not fully understood or investigated and there are several controverting reports regarding …

Redirection Of The Immune Response To Staphylococcus Aureus Biofilm Infection, Anna G. Staudacher

Theses & Dissertations

Staphylococcus aureus (S. aureus) is a leading cause of community- and healthcare-associated infections and has a propensity to form biofilms. Biofilm infections are recalcitrant to host immune-mediated clearance as well as antibiotics, making them exceptionally difficult to eradicate. The biofilm environment has been shown to skew the host immune response towards an anti-inflammatory phenotype, characterized by alternatively activated macrophages, recruitment of myeloid-derived suppressor cells (MDSCs), and minimal neutrophil and T cell infiltrates. Our laboratory has attempted to redirect the host immune response towards one that would favor bacterial clearance by employing strategies to augment pro-inflammatory mechanisms. One such …

Development Of C5ar-Targeted Nanoparticles For Delivery Of Vaccines, Shailendra Bharadwaj Tallapaka Venkata Sesha

Theses & Dissertations

Since the early attempts of Benjamin Jesty at inducing immunity against smallpox and the pioneering work of Edward Jenner, vaccination has been, and continues to remain, the principal method of protection from diseases. However, most of the successful vaccines have been against pathogens that do not have major mechanisms to evade the immune system. So far, many life-threatening diseases like hepatitis C, HIV infection, malaria etc., have been resistant to existing vaccination strategies. Thus, there is an urgent need to develop new vaccination strategies that can generate long-lived protective immunity against such pathogens.

The purpose of this thesis is to …

Identification And Characterization Of An Interferon Stimulated Gene That Restricts Alphavirus Infection And Pathogenesis, Subhajit Poddar

Arts & Sciences Electronic Theses and Dissertations

Viral infection of host cells induces the Type I interferon (IFN) response, which is

characterized by the production of hundreds of IFN-stimulated genes (ISGs). Altogether, these

ISGs function to induce an antiviral state, hindering or blocking various steps of the viral

lifecycle. Many individual ISGs have potent and broad antiviral functions. However elimination

of a single ISG does not completely abrogate protection, suggesting that other ISGs, although

moderate or moderate when considered alone, must work cooperatively to provide optimal

antiviral activity.

In order to identify and characterize novel ISGs, an attenuated strain of the alphavirus

chikungunya (CHIKV-181/25) was tested against …

Expansion Of Microbial Virology By Impetus Of The Reduction Of Viral Dark Matter, Siddharth Ravindran Krishnamurthy

Arts & Sciences Electronic Theses and Dissertations

Modern metagenomic methods have rapidly accelerated the rate of viral discovery. Currently, to discover a novel virus, deep sequencing reads must align to a known reference virus. While alignment is effective at identifying closely related viruses, highly divergent viruses can often share no discernable sequence alignment with known viruses. Therefore, the accurate classification of viral dark matter – metagenomic sequences that originate from viruses but do not align to any reference virus sequences – is one of the major obstacles in not only discovering novel viruses, but also by extension, comprehensively defining the virome. As viral dark matter results fundamentally …

Characterization And Function Of Islet Antigen Presenting Cells During Nod Diabetes, Stephen Thomas Ferris

Arts & Sciences Electronic Theses and Dissertations

Here we characterized the initial antigen presenting cells (APCs) within the islet of Langerhans to ascertain their identity and functional role as it pertains to autoimmune diabetes. The activation of the adaptive immune system is induced by the innate immune system, and more specifically APCs. Therefore, it is crucial to identify the APCs that are initiating T1D in order to elucidate the break in tolerance and intervene in order to inhibit progression. We have found that there is a resident macrophage that is present in all strains of mice. This islet macrophage has a distinct transcriptional profile that is unique …

Expression Profiling Of Non-Coding Rna By Environmental Interactions In Innate Immunity, Jacob R. Longfellow

Electronic Theses and Dissertations

Cystic fibrosis (CF) is a genetic disorder that affects 30,000 people in the United States and currently has no cure. Although CF affects all of the body’s systems, it is largely characterized as a lung disease. CF is caused by a mutation in both copies of the gene for cystic fibrosis transmembrane conductance regulator (CFTR). A mutation in the CFTR gene leads to improper movement of chloride ions and water into the airways, which dysregulates the airway surface liquid volume and composition. Individuals with CF are prone to lung infections due to inefficient bacterial clearance and by the age of …

The Effect Of Antigen Polymorphisms On Serological Antibody Detection Assays Based Upon The, Kristi M. Miley

USF Tampa Graduate Theses and Dissertations

Onchocerca volvulus is a filarial parasite transmitted to humans by female Simulium spp. black flies. Infection with this parasite can cause blindness and severe skin disease among humans in Africa and the Americas. Enzyme-linked Immunosorbent Assay serological testing of OV-16 antigen is a diagnostic tool for determining effective elimination of the parasite. Programs typically rely on OV–16 ELISA to evaluate the progress towards interruption and/or elimination of disease by mass drug distribution of ivermectin and vector larvicidal control efforts. As elimination grows closer, monoclonal antibody positive controls for OV-16 ELISA become important to develop for Onchocerca testing due to the …

Mitochondrial Dynamics Controls T Cell Fate Through Metabolic Programming, Michael Buck

Arts & Sciences Electronic Theses and Dissertations

Activated effector T (TE) cells augment anabolic pathways of metabolism, such as aerobic glycolysis, while memory T (TM) cells engage catabolic pathways, like fatty acid oxidation (FAO). However, signals that drive these differences remain unclear. Mitochondria are metabolic organelles that actively transform their ultrastructure. Therefore, we questioned whether mitochondrial dynamics controls T cell metabolism. We show that TE cells have punctate mitochondria, while TM cells maintain fused networks. The fusion protein Opa1 is required for TM, but not TE cells after infection, and enforcing fusion in TE cells imposes TM cell characteristics and enhances antitumor function. Our data suggest that, …

The Role Of Bhlhe40 In Autoimmune Neuroinflammation And Mycobacterial Infection, Chih-Chung Lin

Arts & Sciences Electronic Theses and Dissertations

The mammalian immune system is composed of innate and adaptive compartments, which cooperate with each other to maintain homeostasis and protect the host from the invasion by a variety of pathogens. The tight control of immune responses is extremely important for all individuals. Here, we discovered that the transcription factor basic helix-loop-helix family, member e40 (Bhlhe40) is a critical protein that regulates the autoimmune ("against self") and anti-microbial ("against non-self") responses of myeloid cells and T lymphocytes. Multiple sclerosis (MS) is a human neuroinflammatory disease in the central nervous system with an autoimmune etiology. We have reported that Bhlhe40 positively …

The Role Of Histidine Rich Protein Ii In Cerebral Malaria, Priya Pal

Arts & Sciences Electronic Theses and Dissertations

Human malaria is caused by five species of Plasmodium. Of these, P. falciparum is the deadliest and is the only species that causes cerebral malaria (CM). CM is a disease of the vascular endothelium characterized by parasite sequestration, increased inflammatory cytokine production, vascular leakage and leukocyte infiltration. A distinguishing feature of P. falciparum infection is the parasite’s production and secretion of histidine-rich protein II (HRPII). HRPII accumulates to high concentrations (up to 100 µg/ml) in serum, which correlates with disease severity. Due to high serum levels of this protein, HRPII has classically been considered a biomarker for P. falciparum infection. …

Epigenetic Activation Of The Mouse T Cell Receptor Beta Recombination Center, Jiangyang Zhao

Arts & Sciences Electronic Theses and Dissertations

Lymphocytes are the work horses of adaptive immunity. Compared to the B lymphocyte lineage, early stage progenitors of T lymphocytes maintain considerable potential for differentiation into other hematopoietic lineages. T lineage commitment requires the continuous coordination of transcription factors (TFs) by Notch1 signaling after multi-potent progenitors (MPPs) migrate to thymus. One of the first hall marks of T lineage commitment is expression of the T cell receptor β (TCRβ), which is encoded by the Tcrb locus following its assembly by V(D)J recombination, a somatic shuffling of the genome that joins one V, one D, and one J gene segment. Tcrb …

Defining The Ontogeny And Functions Of Macrophages In Pancreatic Ductal Adenocarcinoma, Yu Zhu

Arts & Sciences Electronic Theses and Dissertations

The immune system plays an essential role in protecting the host organisms against both foreign invaders and self-attacks arisen within the host, such as tumors. Instead of promoting the long-term fitness of the organism, the immune system is often suppressed or hijacked by tumor cells to accelerate the progression of malignancies. Among the key drivers of immune suppression, macrophages are one of the most abundant immune cells present in tumor tissues. High levels of macrophage infiltration in the malignant tissues correlate with negative patient outcome in many types of cancers, including pancreatic ductal adenocarcinoma (PDAC), one of the most lethal …

B7h6: A Cancer Biomarker For The Development Of Novel Immunotherapy Approaches, Mariana Phillips

Seton Hall University Dissertations and Theses (ETDs)

Cancer-based immunotherapy has led the evolution of biologics that can stimulate immune responses towards tumor eradication. The synthesis of small to intermediate size molecules with the targeting and effector functions of mAb may represent a novel class of immunotherapeutics that may overcome the limitations of their biological counterparts.Towards this objective, B7H6 has been identified as a protein ligand localized on the cell surface of transformed tumor cells. B7H6 binds specifically to the activating receptor NKp30, constitutively expressed on all resting and active NK cells. Upon ligand:receptor binding, B7H6 triggers NK cell activation and release of chemokines and pro-inflammatory cytokines such …

The Effect Of Staphylococcus Aureus On Stiffness Of Cortical Bone, Ariel N. Kunde

Graduate Theses

Osteomyelitis, a term for bone infection, is a common cause of hospitalization in the United States. Infection leading to osteomyelitis is almost always a product of bacterial origin. Although polymicrobial presence is seen at infection sites of osteomyelitis, Staphylococcus aureus is most commonly isolated and found to be the cause of more than 95% of bone infection in adults. This organism is a common commensal of humans that is carried by an estimated 60% of the US population. S. aureus is transferred by infected asymptomatic individuals, and its ability to proliferate under a variety of environmental conditions contributes to the …

Characterization Of Murine Breast Cancer Cell Lines For Anti-Cancer Vaccine, Haven N. Frazier

Biological Sciences Undergraduate Honors Theses

Breast cancer is the most commonly diagnosed cancer in women and the second leading cause of cancer death among women in the United States (1). While treatments involving radiation and chemotherapy currently exist, disease must be detected early in order for the treatments to be somewhat effective, and there is no effective treatment after metastasis occurs (2). Additionally, current therapies do not mitigate tumor immunosuppression. Decreasing the tumor-associated immunosuppressive conditions while activating antitumor immunity could prevent recurrence and metastasis, possibly leading to an effective treatment for cancer (3). Tumor cell vaccines could possibly address this issue and have become a …

Exploring A Novel Nf-ĸb- Inhibiting Nanoparticle For Periodontitis Therapy., Kameswara Satya Srikanth Upadhyayula

Electronic Theses and Dissertations

Periodontitis is an infection-driven inflammatory disease characterized by gingival inflammation and bone loss. The NF-ĸB signaling pathway is pivotal in osteoclastogenesis and infection-induced pro-inflammatory responses. The use of nanoparticles as a vehicle to deliver drug increases stability, loading capacity, and facilitates transmembrane transportation. The hypothesis was that a novel nanoparticle carrying therapeutic NBD inhibitory peptides (NBD-nanoparticles) will inhibit measures of periodontal disease. In this project, we tested the nanoparticles for their ability to directly inhibit osteoclastogenesis and inflammation as an original strategy for periodontitis therapy. We also tested the capability of the nanoparticles to inhibit gingival inflammation and alveolar bone …

Developing Novel Approaches To Improve Response To T Cell Based Cancer Immunotherapy, Rina M. Mbofung

Dissertations & Theses (Open Access)

Recently, T cell based immunotherapies have moved to the forefront of cancer immunotherapy with the success of Adoptive T cell therapy (ACT) and Immune checkpoint blockade.ACT, where patients are treated with tumour infiltrating T cells (TILs), conferred a clinical response rate of ~50%. Treatment with anti-CTLA4 and anti –PD1 therapy, conferred response rates of up to 50%, greatly improving the overall survival of patients with advanced melanoma amongst other cancer types. Despite the encouraging outcomes, there are relatively low response rates coupled with the delay of weeks to months before tumour shrinkage can be appreciated. Thus, understanding what tumour intrinsic …

Peptide Vaccine Formulation Controls The Duration Of Antigen Presentation And Magnitude Of Tumor‐Specific Cd8+ T Cell Response, Hiep Khong

Dissertations & Theses (Open Access)

Despite remarkable progresses in vaccinology, therapeutic cancer vaccines have not achieved their full potential. We previously showed that the duration of antigen presentation critically affected the quantity and quality of T cell response and subsequent anti‐tumor efficacy. Here we describe L‐tyrosine amino acid‐based microparticles as a novel peptide vaccine adjuvant for the induction of tumor‐specific T cells. L‐tyrosine microparticles did not induce inflammasome activation, but instead extended antigen presentation time. The consequent prolongation in antigen presentation translated into prolonged T cell proliferation and superior numbers and anti‐tumor function of vaccination‐induced CD8+ T cells. Indeed, prolonging antigen presentation by repeated injection …