Immunology and Infectious Disease Commons^™

Elucidating The Mechanism Of Action Of Experimental Compound Sw33 In Toxoplasma Gondii, Sean Watson

Theses/Capstones/Creative Projects

In recent years, antimicrobial drug resistance has become widespread and thus triggered an ever-growing need for the development of new, efficacious drug treatments. As an antimicrobial drug is developed, its mechanism of action is often identified before it becomes a potential candidate for clinical use. One potential method for identifying mechanism of action is chemical mutagenesis, in which induction of drug-resistant populations is followed by whole-genome sequencing of several clonal isolates. The subsequent observation of identical point mutations in the same gene across multiple drug-resistant populations can indicate a likely molecular target. However, this technique lacks the capacity to facilitate …

Attenuated Responses To Inflammatory Cytokines In Mouse Embryonic Stem Cells: Biological Implications And The Molecular Basis, Bohan Chen

Master's Theses

Embryonic stem cells (ESCs) have attracted intense interest due to their great potential for regenerative medicine. However, their immune property is an overlooked but a significant issue that needs to be thoroughly investigated not only to resolve the concern for therapeutic applications but also for further understanding the early stage of organismal development. Recent studies demonstrated that ESCs are deficient in innate immune responses to viral/bacterial infections and inflammatory cytokines. Inflammatory conditions generally inhibit cell proliferation, which could be detrimental to ESCs, since cell proliferation is their dedicated task during early embryogenesis. Thus, I hypothesize that the attenuated innate immunity …

The Signaling Pathways Of Metallothionein-Mediated Chemotaxis In Breast Cancer, Jennifer Messina

Honors Scholar Theses

Metallothionein (MT) is a small, thiol rich protein released into the extracellular environment in response to stress. Elevated expression of MT has been linked to many inflammatory diseases including inflammatory bowel diseases, diabetes, and cancer. In breast cancer, high expression of MT has been associated with poor patient prognosis. Previous studies have shown that MT acts as a chemoattractant in lymphocytes, and that UC1MT, a monoclonal anti-MT antibody, can block this chemotactic response. In addition, it has been shown that both Cholera toxin and Pertussis toxin, which are known antagonists of G-protein coupled receptors, can inhibit MT-mediated chemotaxis. Here, I …

Il-6/Jak1 Drives Pd-L1 Phosphorylation And Glycosylation To Promote Cancer Immune Evasion, Li-Chuan Chan

Dissertations and Theses (Open Access)

Glycosylation of immune receptors and ligands, such as T-cell receptor (TCR), major histocompatibility complex (MHC), and co-inhibitory molecules, regulates immune signaling activation, antigen presentation, and immune surveillance. Recent studies revealed that the glycan structures of co-inhibitory molecules are required for receptor-ligand interaction, a critical feature for activating cancer immune evasion. However, it is unclear how oncogenic signaling initiates glycosylation of co-inhibitory molecules to induce immunosuppression. Here we show interleukin (IL)-6-activated Janus kinase 1 (JAK1) phosphorylates programmed death-ligand 1 (PD-L1)-Tyr112, leading to the recruitment of endoplasmic reticulum (ER)-associated N-glycosyltransferase, STT3A, which catalyzes the glycosylation of PD-L1, contributing to its stability. A …

The Characterization Of T-Cell Manufacturing For Adoptive T-Cell Therapies, Amir Alpert

Dissertations and Theses (Open Access)

Adoptive T-cell therapy using genetically modified T cells has emerged as a potential therapeutic option for several malignancies. Central to the production of the cellular therapy is the manufacturing using a stimulation, genetic engineering, and expansion methodology. Within this framework, there is a delicate balance between expansion of the cells to a therapeutically relevant dosage and the need to retain the proliferative potential of the ‘living drug’. I show that as T-cells are expanded for elongated periods of time, they lose their proliferative potential and become functionally senescent despite the presence of multiple proliferative cytokines. In addition, I show that …

Rejuvenation Of The Epigenetic Landscape Of The Aged Brain Through Manipulation Of Circulating Factors, Edward Koellhoffer

Dissertations and Theses (Open Access)

The aging population of the United States is expanding at an alarming rate. The Center for Disease Control and Prevention estimates that the population of those age 65 years and older will reach over 50 million by 2020 and will double to 100 million by 2060. This will not only put a massive strain on national healthcare resources, but will also increase the number of those who are not able to live and function independently. It is becoming increasingly vital to understand how the brain changes with age and mechanisms to possibly protect and rejuvenate the aged brain to a …

Cross-Presentation Is A Source Of Tumor Antigens For Multiple Myeloma Immunotherapy, Alexander A. Perakis

Dissertations and Theses (Open Access)

Cross-presentation is an essential bridge between the innate and adaptive arms of the immune system where antigen presenting cells (APCs) prime cytotoxic T cell responses. We have recently identified cross-presentation as a mechanism by which solid tumors present exogenous antigens. We therefore hypothesized that multiple myeloma would be capable of cross-presentation as these cells are derived from B cells, known APCs. We explored the capacity of multiple myeloma to cross-present PR1, a human leukocyte antigen (HLA)-A2 nonameric peptide that is derived from neutrophil elastase (NE) and proteinase 3 (P3), and the ability to treat multiple myeloma using PR1-targeting immunotherapies. Here …

Development Of A Lectin-Fc Fusion Protein With Antiviral And Anti-Cancer Activity., Matthew William Dent

Electronic Theses and Dissertations

This thesis describes the development of a novel lectin-Fc fusion protein and its antiviral and anti-cancer activity. The molecule, Avaren-Fc (AvFc), is a fusion of a variant of the actinomycete lectin actinohivin (Avaren) and the Fc region of human IgG1, and is selective for the terminal α1,2-mannose residues found at the ends of high-mannose-type glycans that can be found on the surface of certain heavily glycosylated viruses and cancer cells. Here, AvFc was found to be able to neutralize simian immunodeficiency virus as well as Hepatitis C virus with nanomolar IC₅₀ values. Furthermore, AvFc recognizes a number of cell …

Telomeric Dna Damage And Repair Machineries In Hiv Infection, Lam Nguyen

Electronic Theses and Dissertations

In this thesis, we investigated T cell homeostasis and DNA damage repair machineries in HIV infection. We found that the frequencies of CD4T cells were low, which is associated with cell apoptosis in HIV patients compared to healthy subjects. Importantly, these events were closely correlated to the increase in T cell exhaustion, senescence, DNA damage, and telomere attrition. Mechanistically, while the DNA damage sensors Mer11, Rad50, and NBS1 (MRN) complexes remained intact, the ataxia-telangiectasia mutated (ATM) kinase and its downstream checkpoint kinase 2 (CHK2) were significantly inhibited during HIV infection. Additionally, telomeric repeat-binding factor 2 (TRF2) that functions to protect …

Systematic Review Of Gastrointestinal Nematodes Of Horses From Australia, Muhammad A. Saeed, Ian Beveridge, Ghazanfar Abbas, Anne Beasley, Jenni Bauquier, Edwina Wilkes, Caroline Jacobson, Kris J. Hughes, Charles El-Hage, Ryan O'Handley, John Hurley, Lucy Cudmore, Peter Carrigan, Lisa Walter, Brett Tennent-Brown, Martin K. Nielsen, Abdul Jabbar

Maxwell H. Gluck Equine Research Center Faculty Publications

Background: Equine gastrointestinal nematodes (GINs) have been the subject of intermittent studies in Australia over the past few decades. However, comprehensive information on the epidemiology of equine GINs, the efficacy of available anthelmintic drugs and the prevalence of anthelmintic resistance (AR) in Australasia is lacking. Herein, we have systematically reviewed existing knowledge on the horse GINs recorded in Australia, and main aspects of their pathogeneses, epidemiology, diagnoses, treatment and control.

Methods: Six electronic databases were searched for publications on GINs of Australian horses that met our inclusion criteria for the systematic review. Subsets of publications were subjected to review epidemiology, …

Immunogenicity Of Tumor Initiating Stem Cells: Potential Applications In Novel Anticancer Therapy, Durga Khandekar, Suneetha Amara, Venkataswarup Tiriveedhi

Biology Faculty Research

Tumor initiating stem cells (TISCs) are a subset of tumor cells, which are implicated in cancer relapse and resistance to chemotherapy. The metabolic programs that drive TISC functions are exquisitely unique and finely-tuned by various oncogene-driven transcription factors to facilitate pro-cancerous adaptive challenges. While this change in TISC metabolic machinery allows for the identification of associated molecular targets with diagnostic and prognostic value, these molecules also have a potential immunological application. Recent studies have shown that these TISC-associated molecules have strong antigenic properties enabling naïve CD8+T lymphocytes to differentiate into cytotoxic effector phenotype with anticancer potential. In spite of the …

Determining Mediators Of Naive T Cell Motility And Dc Association In The Lymph Node, Janie Rae Byrum

Biomedical Sciences ETDs

To become activated and perform effector functions, naive T cells move within lymph nodes to scan dendritic cells presenting antigen. Previous work has shown naive T cell activation is promoted by interleukin 7 in vivo, and it does so by regulating the T cell:dendritic cell interaction. Our work identifies a novel role for IL-7 in mediating naive T cell motility in the lymph node and promoting T cell association with DCs. Additionally, we have developed a method for analyzing microscopy images, regionalized normalized mutual information, to assess intercellular associations between T cells and other cells within the lymph node. Dendritic …

Lipoarabinomannan From Mycobacterium Smegmatis Stimulates An Inflammatory Response In Raw 264.7 Murine Macrophages, Aysha Zaman

Student Scholar Showcase

Macrophages are a key leukocyte in defense against Mycobacterium tuberculosis infection. The precise mechanism by which M. tuberculosis evades host macrophage defenses remains unknown, so understanding how macrophages interact with cell wall components of mycobacteria is critical. Lipoarabinomannan (LAM) is a glycolipid Toll-like receptor-2 (TLR-2) ligand found on the cell wall of mycobacteria, and is thought to contribute to the cell wall structural integrity. When LAM binds to TLR on host leukocytes, this activates cellular responses and phagocytosis by host macrophages. Nitric oxide production can be used as a measure of inflammatory response and can be evaluated via nitrite response …

Enhancing Immunotherapeutic Interventions For Treatment Of Chronic Lymphocytic Leukemia, Kamira K. Maharaj

USF Tampa Graduate Theses and Dissertations

Chronic lymphocytic leukemia (CLL) is the most common leukemia in developed countries. It is characterized by the accumulation of CD5+ B lymphocytes in the peripheral blood, bone marrow, and lymphoid tissues of affected patients. Patients experience lymphadenopathy, fatigue, and are severely immunocompromised. Management of disease and symptoms is possible with chemo-immunotherapy for higher risk patients; however, CLL remains incurable unless bone marrow transplant is performed. Identification of novel targets and optimization of current therapeutics is therefore still necessary. The new targeted therapies are at the forefront of development for CLL treatment, but it remains challenging to maximize their efficacies while …

The Validity Of Medicare Claims-Based Codes To Identify Nontuberculous Mycobacterial Infection In Patients With Bronchiectasis, Jennifer Ku

OHSU-PSU School of Public Health Annual Conference

Background: Nontuberculous mycobacteria (NTM) is a disease of increasing incidence, causing permanent airway damage leading to destructive pulmonary disease. Medicare claims-based codes have been used to identify NTM infection and to evaluate trends in diagnosis and disease outcomes. However, claims-based codes to identify NTM infection have not been validated.

Methods: We linked patients with a bronchiectasis diagnosis (ICD-9-CM 494.0 or 494.1) excluding cystic fibrosis from the national 2006-2014 Centers for Medicare and Medicaid (Medicare) data to the U.S. Bronchiectasis Research Registry (BRR). The BRR is a national prospective cohort of patients with bronchiectasis, that collects detailed clinical, laboratory, microbiology and …

The Sucking Louse Fauna Of Mongolian Rodents: Host Associations, Molecular Phylogenetics And Description Of Two New Species, Chase N. Robinson

Honors College Theses

This study aimed to screen Mongolian rodents for sucking lice (Insecta: Phthiraptera: Anoplura) to better understand host-parasite associations for this understudied region. Nine species, including 3 previously undescribed, from 4 genera were identified. A molecular phylogeny based on 2 mitochondrial genes of collected louse specimens is included.

The One Health Approach To Toxoplasmosis: Epidemiology, Control, And Prevention Strategies, A. Alonso Aguirre, Travis Longcore, Michelle Barbieri, Haydee Dabritz, Dolores Hill, Patrice N. Klein, Christopher Lepczyk, Emily L. Lilly, Rima Mcleod, Judith Milcarsky, Caroline E. Murphy, Chunlei Su, Elizabeth Vanwormer, Robert Yolken, Grant C. Sizemore

School of Veterinary and Biomedical Sciences: Faculty Publications

One Health is a collaborative, interdisciplinary effort that seeks optimal health for people, animals, plants, and the environment. Toxoplasmosis, caused by Toxoplasma gondii, is an intracellular protozoan infection distributed worldwide, with a heteroxenous life cycle that practically affects all homeotherms and in which felines act as definitive reservoirs. Herein, we review the natural history of T. gondii, its transmission and impacts in humans, domestic animals, wildlife both terrestrial and aquatic, and ecosystems. The epidemiology, prevention, and control strategies are reviewed, with the objective of facilitating awareness of this disease and promoting transdisciplinary collaborations, integrative research, and capacity building among universities, …

Transposon Mutagenesis In Mycobacterium Avium Subspecies Paratuberculosis, John P. Bannantine, Denise K. Zinniel, Raul G. Barletta

School of Veterinary and Biomedical Sciences: Faculty Publications

While transposon mutagenesis has been developed for Mycobacterium avium subspecies paratuberculosis (Map), relatively few laboratories have adopted this important genetic tool to examine gene function and essentiality. Here we describe the construction of a Map transposon library using the Himar1 mariner transposon, but concepts can also be applied to the Tn5367 transposon, which has also been used by our group. Delivery of the transposon is by a temperature-sensitive phagemid, ϕMycoMarT7, and plating transductants requires patience and specialized media due to length of incubation required to observe colonies. Several transposon mutants obtained from these libraries have been tested in vaccine and …

Near-Complete Genome Sequences Of Vesicular Stomatitis Virus Indiana Laboratory Strains Hr And T1026r1 And Plaque Isolates 22-20 And 22-25, Thomas M. Russell, Evan E. Santo, Lisa Golebiewski, Nathan S. Haseley, Maureen Ferran

Articles

We report four near-complete genome sequences of vesicular stomatitis virus (VSV) Indiana obtained with Sanger and Illumina next-generation sequencing, namely, laboratory strains HR (heat resistant) and T1026R1 and isolates 22-20 and 22-25. Previously, only the M gene of these viruses had been sequenced, and these sequences were not deposited in GenBank.

Regulation Of Immune Cell Activation And Functionby The Nbmpp2 Protein Andthe Cd5 Co-Receptor, Claudia Mercedes Freitas

Theses and Dissertations

According to the centers for disease control and prevention (CDC) and the world healthorganization (WHO), heart disease and immune related diseases such as diabetes and cancer areamong the leading causes of death around the world. Thus, the regulation of the function ofimmune cell plays a key role in health and disease. Calcium (Ca2+) ions play a critical role inimmune cell activation, function and in a robust immune response. Defects in Ca2+ signalinginfluences the development of cardiac disease, Alzheimer disease, immune cell metabolism,muscle dysfunction, and cancer. Each immune cell is unique in its activation and function,making it relevant to understand how …

Z4, A Slow Puncture: An Autoethnographic Exploration Of Language, Embodiment, And Meaning-Making, Charlotte Rose Samuels

Independent Study Project (ISP) Collection

In my ISP, I explored language as it relates to the ways in which people living in Cato Manor make sense of HIV/AIDS in their community. With 7.1-7.2 million people living with HIV (PLWHIV) in South Africa, individuals across the country are either infected or affected by illness. KwaZulu-Natal (KZN), the province with the highest rate of HIV, is also the province that was surveyed with the disproportionately highest internal stigma rates for PLWHIV. High prevalence of HIV, particularly in KZN, calls for a constant contextualization of life in the presence of illness.

Throughout the world, metaphor and symbolism is …

From The American People: An Autoethnographic Exploration Of South African Ngos' Perceptions Of Pepfar, Antonia Asher

Independent Study Project (ISP) Collection

The aim of this research was to understand what the ideal partnership would be between United States (US) governmental aid agencies and South African non-governmental organizations (NGOs), specifically concerning HIV/AIDS programs funded by the US President’s Emergency Plan for AIDS Relief (PEPFAR), from the perspective of NGOs. PEPFAR is the largest relief fund for a single disease; thus, I additionally sought to deeply reflect upon myself as a US citizen in South Africa, a country that has received trillions of dollars from taxpayers such as myself.

To accomplish this, I interviewed NGO staff about the nature of current partnerships, outcomes …

Vaccine Hesitancy In The United States And Switzerland, Anna E. Lunderberg

Independent Study Project (ISP) Collection

Vaccine hesitancy (VH), or the reluctance or refusal to participate in vaccination programs, is a complex phenomenon with far-reaching impacts on society. VH can impact vaccine uptake and facilitate subsequent outbreaks, as seen with the case of measles. Perceptions of vaccination are similar in the United States and Switzerland, and misinformation in each country contributed to VH through impaired parental risk-benefit analysis; parental analysis and subsequent VH is associated with both anti-vaccination messages gaining prominence and a decrease in the public perception of the health risk from vaccine-preventable diseases (VPDs). There are many proposed strategies for addressing VH on both …

The Ecological Niche Of Echinococcus Multilocularis In North America: Understanding Biotic And Abiotic Determinants Of Parasite Distribution With New Records In New Mexico And Maryland, United States, Sebastian Botero-Cañola, Altangerel Tsogtsaikhan Dursahinhan, Sara E. Rácz, Parker V. Lowe, John E. Ubelaker, Scott Lyell Gardner

Scott L. Gardner Publications

English abstract: Understanding the factors shaping the niche of parasites and its expression over geographical space and through time continues to be a modern scientific challenge with the results of research in this area directly influencing both theoretical and applied biology. This is especially important for proactive management of zoonotic parasites such as Echinococcus multilocularis, the etiologic agent of alveolar echinococcosis. Echinococcus multilocularis has a Holarctic distribution; with its geographic range and prevalence increasing recently in areas of the western Palearctic, while its distribution dynamics are poorly understood in the Nearctic. In this paper, we use an ecological niche …

Impact Of Intrinsic Physiological Factors In The Population Recovery Of Myotis Lucifugus (Little Brown Myotis) From White-Nose Syndrome, Caroline Burke, Caitlin Looney, Alissah Sillah, Christopher Richardson

Lesley University Community of Scholars Day

White-nose Syndrome (WNS) has decimated populations of hibernating bats in the US. In particular, Myotis lucifugus (little brown myotis) has been one of the most affected. We investigated the energetic cost of innate immune response and Pseudogymnoascus destructans (Pd) fungal activity on post-hibernating little brown myotis and the link with the recovery of local populations in New England from WNS. We captured bats at one of each of 4 colonies in Eastern Massachusetts and Southern New Hampshire, consecutively, every 14 days to minimize disturbance to the colony. Blood samples were collected from each bat. Respirometry trials were performed on each …

Abrogation Of Endogenous Glycolipid Antigen Presentation On Myelin-Laden Macrophages By D-Sphingosine Ameliorates The Pathogenesis Of Experimental Autoimmune Encephalomyelitis, Yi Ban, Wenjuan Dong, Lixing Zhang, Tian Zhou, Ahmad Sabri Altiti, Khaleel Ali, David R. Mootoo, Victoria A. Biaho, Timothy Hla, Yi Ren, Xiaojing Ma

Publications and Research

Background: Although myelin is composed of mostly lipids, the pathological role of myelin lipids in demyelinating diseases remains elusive. The principal lipid of the myelin sheath is b-galactosylceramide (b-Galcer). Its a-anomer (a-Galcer) has been demonstrated to be antigenically presented by macrophages via CD1d, a MHC class I-like molecule. Myelin, which is mostly composed of b-Galcer, has been long considered as an immunologically-inert neuron insulator, because the antigen-binding cleft of CD1d is highly a-form-restricted.

Results: Here, we report that CD1d-mediated antigenic presentation of myelin-derived galactosylceramide (Mye-GalCer) by macrophages contributed significantly to the progression of experimental autoimmune encephalomyelitis (EAE). Surprisingly, this presentation …

Environmental Transmission Of Toxoplasma Gondii: Oocysts In Water, Soil And Food, Karen Shapiro, Lillian Bahia-Oliveira, Brent Dixon, Aurélien Dumètre, Luz A. De Wit, Elizabeth Vanwormer, Isabelle Villena

School of Veterinary and Biomedical Sciences: Faculty Publications

Toxoplasma gondii is a zoonotic protozoan parasite that can cause morbidity and mortality in humans, domestic animals, and terrestrial and aquatic wildlife. The environmentally robust oocyst stage of T. gondii is fundamentally critical to the parasite's success, both in terms of its worldwide distribution as well as the extensive range of infected intermediate hosts. Despite the limited definitive host species (domestic and wild felids), infections have been reported on every continent, and in terrestrial as well as aquatic environments. The remarkable resistance of the oocyst wall enables dissemination of T. gondii through watersheds and ecosystems, and long-term persistence in diverse …

Understanding Immunometabolic And Suppressive Factors That Impact Cancer Development, Rebecca Swearingen Hesterberg

USF Tampa Graduate Theses and Dissertations

The immune system is responsible for surveillance against pathogens and malignancies and adoptive transfer of antigen-specific T is a powerful new cancer treatment option. There is a clinical need to understand more about the normal regulatory processes that prevent immunosurveillance and how to manipulate this for clinical benefit. This project aims to understand T cells from three different angles. First, the biological role of the negative regulator cereblon (CRBN) was investigated in CD8+ T cells and my studies showed that higher levels of specific derivatives downstream of the amino acid glutamine may be beneficial to T cells in the immune …

Kinetic Analysis And Epitope Mapping Of Monoclonal Antibodies To Salmonella Typhimurium Flagellin Using A Surface Plasmon Resonance Biosensor, Devendra Bhandari, Fur-Chi Chen, Shreya Hamal, Roger C. Bridgman

Human Sciences Faculty Research

Salmonella Typhimurium is one of the leading causes of foodborne diseases worldwide. Biosensors and immunoassays utilizing monoclonal antibodies are widely used for the detection and subtyping of S. Typhimurium. However, due to insufficient information on the nature of binding with S. Typhimurium flagellin, the selection of appropriate antibodies for assay development is a cumbersome task. Hence, we aimed to compare the binding kinetics of a panel of monoclonal antibodies and their relative binding sites to flagellin antigen using a surface plasmon resonance biosensor. Initially, the flagellin was captured on the sensor surface through an immobilized anti-flagellin antibody. The interactions of …

Targeted Therapy For The Future: The Use Of Novel Antimicrobial Peptides Against P. Aeurginosa, Matthew Froid

UNO Student Research and Creative Activity Fair

Pathogenic bacteria, such as the gram-negative bacterium Pseudomonas aeruginosa, are becoming resistant to our current arsenal of antibiotics at an alarming rate. P. aeruginosa is a leading cause of nosocomial acquired infections and is a primary co-morbidity in patients with compromised immune systems. One potential source of new antibiotic agents is antimicrobial peptides. Antimicrobial peptides (AMPs) are small proteins, and some have shown a high degree of efficacy and broad-spectrum activity against both Gram-positive and Gram-negative bacteria. An experimental AMP that has been developed by Dr. Wang at UNMC, DASamp2, has shown to be effective against virulent bacteria, including P. …