Immunology and Infectious Disease Commons^™

The Surveillance Of Gastrointestinal Parasitic Nematodes Of Northwest Arkansas Dairy Cattle Using Traditional And Genetic Parasitological Identification Procedures, Eva M. Wray

Graduate Theses and Dissertations

Traditional and genetic parasitological identification procedures were compared using naturaland artificial nematode parasite infections in Holstein steer calves. The traditional parasitological procedures measured fecal egg counts, coprocultures with subsequent larval collection and adult nematodes collected at necropsy. The genetic identification procedures measured ITS-2 sequences extracted from different stages of nematode development: raw feces, concentrated nematode eggs, third stage larvae and adults. The primary nematodes observed were Cooperia oncophora, Cooperia punctata and Ostertagia ostertagi. The traditional techniques were not significantly different from one another, while the genetic sequencing showed variation amongst the different procedures. The raw feces sequences showed the most …

Role Of Β-Glucan Structure In Dectin-1 Homo- And Hetero-Oligomerization In Innate Anti-Fungal Immunity, Eduardo U. Anaya

Biomedical Sciences ETDs

Dectin-1A is a C-type Lectin innate immunoreceptor that recognizes β-(1,3)-glucan, a structural component of Candida species cell walls. Dectin-1 has eight alternative splice isoforms including, A and B. Innate immunocytes can express one or both isoforms, but neither their relative responsiveness to β-glucan nor the potential for inter-isoform signaling cross-talk is well understood. In this study, we determine how the different structures of soluble β-glucans affect both isoforms and unravel how differences in glucan structure impact the earliest events in Dectin-1 signaling. Using quantitative microscopy techniques, we explored the role of glucan structure on Dectin-1A oligomerization, which is thought to …

Inducible Epithelial Resistance Against Acute Viral Pneumonia And Chronic Asthma, Shradha Wali

Dissertations and Theses (Open Access)

Viral pneumonia remains a global health threat despite worldwide vaccination and therapeutic programs. The influenza pandemic of 1918 and SARS-CoV2 pandemic of 2019-2020 are cautionary reminders demanding the need for novel treatment strategies. Moreover, in addition to causing acute disease, respiratory virus infections are often complicated by chronic lung pathologies, such as asthma induction, progression, and exacerbation. We have reported that mice treated with a combination of inhaled Toll-like receptor (TLR) 2/6 and TLR 9 agonists (Pam2-ODN) to stimulate innate immunity are broadly protected against respiratory pathogens, but the mechanisms underlying this protection remain incompletely elucidated. Here, we show in …

Subclonal Evolution Of Chronic Lymphocytic Leukemia After Allogeneic T Cell Therapies, Haven Garber

Dissertations and Theses (Open Access)

Subclonal evolution of chronic lymphocytic leukemia after allogeneic T-cell therapies

Haven Garber, MD

Advisory Professor: Jeffrey Molldrem, MD

Intratumoral genetic heterogeneity describes the molecular differences among subclones within a tumor and is a major barrier to effective therapy in many solid and liquid cancers, including chronic lymphocytic leukemia (CLL). Rare, treatment-resistant subclones can expand to compose relapsed disease during tumor evolution. Examination of malignant evolution in the context of specific treatment provides insight into the molecular lesions that mediate therapeutic response and resistance. Both chemotherapy and targeted therapy were shown to precipitate CLL subclonal evolution. We hypothesized that allogeneic T-cell …

Reversal Of Neurodegeneration By Engineered Monocytes In Alzheimer’S Disease, Chao-Hsien Chen

Dissertations and Theses (Open Access)

The health challenges posed by Alzheimer’s disease (AD) continue to grow as societies age worldwide. Accumulation of Tau-associated pathology correlates with clinical cognitive deterioration in AD. Resident myeloid cells within the central nervous system (CNS) have a limited capacity to uptake and degrade Tau; however, the resulting secretion of proinflammatory cytokines only acts to accelerate neurodegeneration. Therapeutic antibodies can reduce the neurotoxic oligomeric form of Tau (o-Tau), but in doing so they also aggravate inflammation. Attenuating mutation of the antibody Fc region can silence inflammation but also eliminates its capacity to mediate o-Tau clearance by CNS myeloid cells. Thus, there …

Elucidating The Roles Of Il-15 In The Tumor Microenvironment, Rosa Maria Santana Carrero

Dissertations and Theses (Open Access)

ELUCIDATING THE ROLES OF IL-15 IN THE TUMOR MICROENVIRONMENT

Rosa M. Santana Carrero, B.S.

Advisory Professors: Shao-Cong Sun, Ph.D. & Kimberly S. Schluns, Ph.D.

Interleukin-15 (IL-15) is a factor that promotes activation, proliferation, cytotoxicity, and survival of CD8 T cells and NK cells, and has been shown to have anti-tumor effects. Moreover, loss of IL-15 expression in human colorectal tumors correlates with increased risk of relapse, diminished survival, decreased density and proliferation of T cells. All together these findings suggest that IL-15 expressed locally in the tumor microenvironment (TME) is an important mediator of anti-tumor responses by tumor infiltrating lymphocytes …

Fibroblast Heterogeneity In Pancreatic Cancer Immunity, Josephine Darpolor

Dissertations and Theses (Open Access)

Fibroblasts are a unique cell type defined by their mesenchymal phenotype and exclusion from epithelial, immune, and endothelial cell subsets. Although well studied in wound healing, cancer associated fibroblasts (CAFs) are incredibly heterogeneous, leading to contradictions as to the roles CAFs play in the tumor microenvironment (TME). CAFs were thought to be a barrier to treatment of pancreatic ductal adenocarcinoma (PDAC). However, general stromal targeting strategies have largely failed in the clinic likely due to the heterogeneity of CAFs in the TME. Therefore, our groups and others have worked to unravel the heterogeneity of CAFs in PDAC. In the works …

Increasing Antibiotic Resistance In Shigella Bacteria In The United States, William J. Pharr

The Corinthian

Shigella bacteria cause half a million infections, 6,000 hospitalizations, and 70 deaths annually in the United States. These bacteria are of particular concern due to their high survivability, low infectious dose, and high adaptability. Cases of shigellosis from Shigella sonnei are becoming a more prevalent issue in the U.S. as the bacteria continues to develop higher resistance to today’s strongest antibiotics. Much of this resistance is connected to the exchange of genes between strains of Shigella due to insertion sequences (IS), intercontinental travel, and men who have sex with men (MSM). As a result of increased resistance, the use of …

Epidemiology And Pathophysiology Of Common Skin Diseases In West Africa: An Immunodermatological Framework, Osazomon Imarenezor

All HCAS Student Capstones, Theses, and Dissertations

This capstone reviews the common skin diseases on a global scale. With these dermatoses being further funneled into Africa and then magnified into common West African dermatoses, the meta-analyses of literature available paints a clear picture of the epidemiological & pathological factors and their contribution to the skin disease. Each article analysed in this analysis was taken from a 20-year span of January 2000 to December 2019. The selection of articles was fine-tuned by identifying the distribution of skin disease, revealing the populations affected (age, gender, ethnicity, etc), the main causes, country of origin, the prognosis of disease, and the …

Strategies To Improve Coverage Of Typhoid Conjugate Vaccine (Tcv) Immunization Campaign In Karachi, Pakistan, Farah Qamar Naz, Rabab Batool, Sonia Qureshi, Miqdad Ali, Tahira Sadaf, Junaid Mehmood, Khalid Iqbal, Akram Sultan, Noah Duff, Mohammad Tahir Yousafzai

Department of Paediatrics and Child Health

The emergence and spread of extensively drug-resistant (XDR) typhoid in Karachi, Pakistan led to an outbreak response in Lyari Town, Karachi utilizing a mass immunization campaign with typhoid conjugate vaccine (TCV), Typbar TCV®. The mass immunization campaign, targeted Lyari Town, Karachi, one of the worst affected towns during the XDR typhoid outbreak. Here we describe the strategies used to improve acceptance and coverage of Typbar TCV in Lyari Town, Karachi. The mass immunization campaign with Typbar TCV was started as a school- and hospital-based vaccination campaign targeting children between the age of 6 months to 15 years old. A dose …

Applying Immuno-Epidemiology Principles To Violence, Anna H. Sisk, Nina H. Fefferman, Judy Day, Patricia Bamwine

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Modeling And Preparedness: The Transmission Dynamics Of Covid-19 Outbreak In Provinces Of Ecuador, Carlos E. Bustamante Orellana, Jordy Cevallos-Chavez, Cesar Montalvo, Jeff Sulliavan, Edwin Michael, Anuj Mubayi

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

In Silico Modelling For The Treatment Of Gastric Cancer, Leonardo F. Martinez, Diana Gamboa, Paul A. Valle

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Mobility Impact In The Spreading Of Covid-19 In Ecuador, Jordy Cevallos-Chavez, Carlos E. Bustamante Orellana, Cesar Montalvo, Anuj Mubayi, Edwin Michael, Edwin Michael

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Neutrophil-To-Lymphocyte Ratio: A Biomarker To Monitor The Immune Status Of Astronauts, Amber M. Paul, Siddhita D. Mhatre, Egle Cekanaviciute, Ann-Sofie Schreurs, Candice G.T. Tahimic, Ruth K. Globus, Sulekha Anand, Brian E. Crucian, Sharmila Bhattacharya

Publications

A comprehensive understanding of spaceflight factors involved in immune dysfunction and the evaluation of biomarkers to assess in-flight astronaut health are essential goals for NASA. An elevated neutrophil-to-lymphocyte ratio (NLR) is a potential biomarker candidate, as leukocyte differentials are altered during spaceflight. In the reduced gravity environment of space, rodents and astronauts displayed elevated NLR and granulocyte-to-lymphocyte ratios (GLR), respectively. To simulate microgravity using two well-established ground-based models, we cultured human whole blood-leukocytes in high-aspect rotating wall vessels (HARV-RWV) and used hindlimb unloaded (HU) mice. Both HARV-RWV simulation of leukocytes and HU-exposed mice showed elevated NLR profiles comparable to spaceflight …

Investigating Microbial And Host Factors That Modulate Severity Of Clostridioides Difficile Associated Disease, Armando Lerma

Department of Food Science and Technology: Dissertations, Theses, and Student Research

Clostridioides difficile is recognized as one of the most important pathogens in hospital and community healthcare settings. The clinical outcome of infection of toxigenic C. difficile infection (CDI) ranges from asymptomatic colonization to fulminant pseudomembranous colitis and death. In recent studies, it has been suggested that a high proportion of nosocomial CDI cases are transmitted from asymptomatic carriers which might be acting as infection reservoirs. Understanding what causes the different responses to infection could lead to the development of novel prevention and treatment strategies. Although several explanations have been proposed to explain variations in susceptibility, understanding of the exact mechanisms …

A Statistical Learning Regression Model Utilized To Determine Predictive Factors Of Social Distancing During Covid-19 Pandemic, Timothy A. Smith, Albert J. Boquet, Matthew V. Chin

Publications

In an application of the mathematical theory of statistics, predictive regression modelling can be used to determine if there is a trend to predict the response variable of social distancing in terms of multiple predictor input “predictor” variables. In this study the social distancing is measured as the percentage reduction in average mobility by GPS records, and the mathematical results obtained are interpreted to determine what factors drive that response. This study was done on county level data from the state of Florida during the COVID-19 pandemic, and it is found that the most deterministic predictors are county population density …

Chain-Selective Isotopic Labeling Of The Heterodimeric Type Iii Secretion Chaperone, Scc4:Scc1, Reveals The Total Structural Rearrangement Of The Chlamydia Trachomatis Bi-Functional Protein, Scc4, Thilini O. Ukwaththage, Samantha M. Keane, Li Shen, Megan A. Macnaughtan

School of Medicine Faculty Publications

Scc4 is an unusual bi-functional protein from Chlamydia trachomatis (CT) that functions as a type III secretion system (T3SS) chaperone and an RNA polymerase (RNAP)-binding protein. Both functions require interactions with protein partners during specific stages of the CT developmental cycle. As a T3SS chaperone, Scc4 binds Scc1 during the late stage of development to form a heterodimer complex, which chaperones the essential virulence effector, CopN. During the early-middle stage of development, Scc4 regulates T3SS gene expression by binding the σ66-containing RNAP holoenzyme. In order to study the structure and association mechanism of the Scc4:Scc1 T3SS chaperone complex using nuclear …

Field Evaluation Of Recombinant Antigen Elisa In Detecting Zoonotic Schistosome Infection Among Water Buffaloes In Endemic Municipalities In The Philippines, Jose Ma. M. Angeles, Yasuyuki Goto, Masahi Kirinoki, Elena A. Villacorte, Kharleezelle J. Moendeg, Pilarita T. Rivera, Yuichi Chigusa, Shin-Ichiro Kawazu

Biology Faculty Publications

In this study, we investigated the use of recombinant antigens thioredoxin peroxidase-1 (rSjTPx-1) and tandem repeat rSj1TR in evaluating the antibody positivity rates of Schistosoma japonicum infection among water buffaloes from four endemic areas in the Philippines, two municipalities with high endemicity (Calatrava, Negros Occidental and Catarman, Northern Samar) and two municipalities nearing elimination with no cases of human schistosomiasis (Talibon and Trinidad, Bohol). These recombinant antigen ELISA assays were compared with other diagnostic tests including SEA-ELISA, FECT, and fecal-based PCR. Results showed that rSj1TR-ELISA has the highest agreement with PCR in all study areas. Furthermore, significant positivity rates among …

Aci-35 And Aadvac1 Active Immunotherapy As Preventative Treatment Options For Chronic Traumatic Encephalopathy, Emily C. Boehlein

Selected Honors Theses

One of the most common, as well as one of the most dangerous injuries amongst athletes today is mild traumatic brain injury (mTBI), commonly known as concussion. Aside from physical symptoms such as nausea, dizziness, and headaches; concussions have can have longterm effects on brain physiology. A common neurological disease that can result from multiple concussions is Chronic Traumatic Encephalopathy (CTE), characterized by symptoms such as severe depression, anxiety, confusion, and aggression; amongst others.1 On the cellular level, CTE is classified by a unique pathway that leads to the hyperphosphorylation of tau protein and subsequent clumping of tau-containing neurofibrillary tangles …

Can Viruses Cause Lupus?, Stephen I. Reeder

Selected Honors Theses

Like so many autoimmune diseases, the exact cause of systemic lupus erythematosus (SLE) remains unknown. Evidence points to both genetics and environment playing roles in the onset of the disease, but neither acts independent of the other. Genetics are the easier of the two to study with recent advances in the field making it easier to isolate genes shared by individuals with the disease. However, genetic studies reveal that there is almost certainly an environmental component to the development of SLE. The underlying pathology and existing research on environmental contributors to the development of SLE suggest that viruses could potentially …

Society For Immunotherapy Of Cancer Clinical And Biomarkers Data Sharing Resource Document: Volume I-Conceptual Challenges., Sergio Rutella, Michael A Cannarile, Sacha Gnjatic, Bruno Gomes, Justin Guinney, Vaios Karanikas, Mohan Karkada, John M Kirkwood, Beatrix Kotlan, Giuseppe V Masucci, Els Meeusen, Anne Monette, Aung Naing, Vésteinn Thorsson, Nicholas Tschernia, Ena Wang, Daniel K Wells, Timothy L Wyant, Alessandra Cesano

Articles, Abstracts, and Reports

The sharing of clinical trial data and biomarker data sets among the scientific community, whether the data originates from pharmaceutical companies or academic institutions, is of critical importance to enable the development of new and improved cancer immunotherapy modalities. Through data sharing, a better understanding of current therapies in terms of their efficacy, safety and biomarker data profiles can be achieved. However, the sharing of these data sets involves a number of stakeholder groups including patients, researchers, private industry, scientific journals and professional societies. Each of these stakeholder groups has differing interests in the use and sharing of clinical trial …

Horizontal Genetic Exchange Of Chromosomally Encoded Markers Between Campylobacter Jejuni Cells, Deepti Pranay Samarth, Young Min Kwon

Poultry Science Faculty Publications and Presentations

Many epidemiological studies provide us with the evidence of horizontal gene transfer (HGT) contributing to the bacterial genomic diversity that benefits the bacterial populations with increased ability to adapt to the dynamic environments. Campylobacter jejuni, a major cause of acute enteritis in the U.S., often linked with severe post-infection neuropathies, has been reported to exhibit a non-clonal population structure and comparatively higher strain-level genetic variation. In this study, we provide evidence of the HGT of chromosomally encoded genetic markers between C. jejuni cells in the biphasic MH medium. We used two C. jejuni NCTC-11168 mutants harbouring distinct …

‘Coronated’ Consumption In The Viral Market, Soonkwan Hong

Markets, Globalization & Development Review

The universal exposure to the virus has disrupted institutions, redefined values, and reshaped systems, including the market. Idling, uncertainty, and liquidity encapsulate the ever-precarious individual lives and the reflexive socio-politico-cultural changes. These conditions and consequences nonetheless create paradoxical opportunities in the viral market. The new meaning of connectivity that promotes high-viscosity relationships and high-visibility identities will transform the market to better acknowledge and support humans and the new sociality.

Analyses Of The Expression, Immunohistochemical Properties And Serodiagnostic Potential Of Schistosoma Japonicum Peroxiredoxin-4, Minh-Anh Dang-Trinh, Jose Ma. M. Angeles, Kharleezelle J. Moendeg, Adrian Miki C. Macalanda, Thu-Thuy Nguyen, Luna Higuchi, Shotaro Nakagun, Masahi Kirinoki, Yuichi Chigusa, Yasuyuki Goto, Shin-Ichiro Kawazu

Biology Faculty Publications

Background

Schistosoma japonicum, which inhabits the mesenteric vein of the mammalian hosts for about 20 to 30 years, is subjected to the oxidative stresses from the host defense mechanism during their intra-mammalian stages. To counteract this host immune attack, the parasite utilizes their antioxidant system for survival inside the host. Peroxiredoxins (Prxs), thiol-specific antioxidant proteins, play an essential role for protecting the parasite against oxidative stress by reducing hydrogen peroxide to water. Only three types of 2-Cys Prxs have been previously characterized in S. japonicum whereas a fourth Prx has been identified for Schistosoma mansoni as Prx-4. A sequence …

Efficacy And Safety Of First-Line Avelumab In Patients With Advanced Non-Small Cell Lung Cancer: Results From A Phase Ib Cohort Of The Javelin Solid Tumor Study., Claire F Verschraegen, Guy Jerusalem, Edward F Mcclay, Nicholas Iannotti, Charles H Redfern, Jaafar Bennouna, Franklin L Chen, Karen Kelly, Janice Mehnert, John C Morris, Matthew H Taylor, David Spigel, Ding Wang, Hans Juergen Grote, Dongli Zhou, Neru Munshi, Marcis Bajars, James L Gulley

Articles, Abstracts, and Reports

INTRODUCTION: Avelumab, an antiprogrammed death ligand-1 antibody, is approved as a monotherapy for treatment of metastatic Merkel cell carcinoma and advanced urothelial carcinoma, and in combination with axitinib for advanced renal cell carcinoma. We report the efficacy and safety of first-line avelumab in advanced non-small cell lung cancer (NSCLC).

METHODS: In a phase I expansion cohort of the JAVELIN Solid Tumor trial, patients with treatment-naive, metastatic, or recurrent NSCLC received 10 mg/kg avelumab intravenously every 2 weeks. Endpoints included best overall response, duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety.

RESULTS: Overall, 156 patients were enrolled …

Neoantigen-Specific Cd4(+) T-Cell Response Is Critical For The Therapeutic Efficacy Of Cryo-Thermal Therapy, Peng Peng, Hong-Ming Hu, Ping Liu, Lisa X Xu

Articles, Abstracts, and Reports

Background: Traditional tumor thermal ablations, such as radiofrequency ablation (RFA) and cryoablation, can result in good local control of tumor, but traditional tumor thermal ablations are limited by poor long-term survival due to the failure of control of distal metastasis. Our previous studies developed a novel cryo-thermal therapy to treat the B16F10 melanoma mouse model. Long-term survival and T-cell-mediated durable antitumor immunity were achieved after cryo-thermal therapy, but whether tumor antigen-specific T-cells were augmented by cryo-thermal therapy was not determined.

Methods: The long-term antitumor therapeutic efficacy of cryo-thermal therapy was performed in B16F10 murine melanoma models. Splenocytes derived from mice …

The Kinetics Of Influenza A (A/California/4/2009-H1n1) And B (B/Phuket/3073/2013 (Byam), B/Brisbane/60/2008 (Bvic)) Virus Infection In Ferrets, Demi L. Erickson

Honors Thesis

Influenza is a persistent threat to individual and global health. Seasonal influenza kills nearly 500,000 people globally each year. Influenza viruses have circulated within the human population, causing a significant disease burden. In order to create the most effective antiviral therapies, knowledge concerning all lineages of influenza must be studied accurately and thoroughly. The influenza virus itself is not always responsible for these mortalities, rather, the secondary bacterial infections associated with death. In order to protect the population and examine the secondary infections that arise, the kinetics of influenza must be studied entirely. To understand the kinetics, researchers are turning …

The Impact Of Myeloid-Mediated Co-Stimulation And Immunosuppression On The Anti-Tumor Efficacy Of Adoptive T Cell Therapy, Pasquale Patrick Innamarato

USF Tampa Graduate Theses and Dissertations

Adoptive T cell therapy (ACT) in combination with lymphodepleting chemotherapy is an effective strategy to induce the eradication of tumors, providing long-term regression in cancer patients. However, only a minority of patients that receive ACT with tumor infiltrating lymphocytes (TILs) exhibit durable benefit. Thus, there is an urgent need to define strategies that potentiate anti-tumor activity conducted by adoptively transferred T cells. In these studies, we aimed to identify novel strategies to enhance the therapeutic efficacy of ACT. Accordingly, we describe the disparate roles of myeloid cells in the context of ACT characterized by the augmentation of TIL proliferation in …

Development, Expansion And Role Of Myeloid-Derived Suppressor Cells In Post-Sepsis Immune Suppression, Tuqa Alkhateeb

Electronic Theses and Dissertations

Myeloid-derived suppressor cells (MDSCs) numbers increase significantly in sepsis and are associated with high mortality rates. These myeloid cell precursors promote immunosuppression, especially in the late (post sepsis) stage. However, the mechanisms that underlie MDSC expansion and programming are not completely understood. To investigate these mechanisms, we used a cecal-ligation and puncture (CLP) mouse model of polymicrobial sepsis that progresses from an early/acute proinflammatory phase to a late/chronic immunosuppressive phase. Previous studies in our laboratory showed that microRNA (miR)-21 and miR-181b elevate levels of the transcription factor nuclear factor 1 (NFI-A) that promotes MDSC expansion. We report here that miR-21 …