Immunology and Infectious Disease Commons^™

The Role Of Hdac6 In Periodontal Inflammation, Hannah S. Lohner

Theses and Dissertations

Periodontal disease is a polymicrobial infection-induced chronic inflammatory disease and results in irreversible tissue damage and bone loss. While bacteria play a large role in the initiation of this disease, excessive and prolonged inflammatory immune responses are fundamental for its progression, making host directed therapy (HDT) a possible and potentially valuable treatment. Histone Deacetylase 6 (HDAC6) is an enzyme that removes acetyl groups from both histone and non-histone proteins, giving it a potential role in regulating inflammation initiated by pathogenic oral bacteria. Previous studies indicated that HDACs act as a bivalent regulator in inflammatory responses; however, the role that HDAC6 …

Autotaxin Suppresses Cytotoxic T Cells Via Lpar5 To Promote Anti-Pd-1 Resistance In Non-Small Cell Lung Cancer, Jessica M Konen, B Leticia Rodriguez, Haoyi Wu, Jared J Fradette, Laura Gibson, Lixia Diao, Jing Wang, Stephanie Schmidt, Ignacio I Wistuba, Jianjun Zhang, Don L Gibbons

Faculty, Staff and Student Publications

Non-small cell lung cancers that harbor concurrent KRAS and TP53 (KP) mutations are immunologically warm tumors with partial responsiveness to anti-PD-(L)1 blockade; however, most patients observe little or no durable clinical benefit. To identify novel tumor-driven resistance mechanisms, we developed a panel of KP murine lung cancer models with intrinsic resistance to anti-PD-1 and queried differential gene expression between these tumors and anti-PD-1-sensitive tumors. We found that the enzyme autotaxin (ATX), and the metabolite it produces, lysophosphatidic acid (LPA), were significantly upregulated in resistant tumors and that ATX directly modulated antitumor immunity, with its expression negatively correlating with total and …

The Development Of Fetal Immunity From In Utero To Shortly After Birth And Complications That Can Arise From Improper Functioning, Marlee Curnutt

Masters Projects

The development of the immune system in humans is highly complex and requires precise timing which is still debated today. Research has shown IL-10 and T-regulatory cells play a significant role in the proper development of the immune system from in utero continuing into months after birth. These components and various cytokines continue to be guiding factors supplemented by the mother via placenta and breastfeeding. The dysregulation of immune development can have detrimental effects on the infant and may lead to autoimmune disorders. In this paper, we aim to further understand the development of the immune system from fetal to …

Characterization Of The Immunoglobulin Lambda Chain Across Diverse Human Populations., William Gibson

Electronic Theses and Dissertations

The adaptive immune system relies on a diverse set of over one hundred immunoglobulin (IG) genes across three genomic loci that are variably combined to form antibodies (Ab). The IG Lambda locus is one of two loci which encodes the IG light chain. The complexity of the IGL locus severely limits the effective use of standard short-read sequencing, limiting our knowledge of population diversity in these loci. We leveraged single molecule real-time (SMRT) long-read sequencing in conjunction with IGL-targeted DNA capture to develop the method IG-Cap for accurate and high-throughput sequencing of the IGL locus. We benchmarked this method using …

Unveiling Immune Checkpoint Therapy Resistance Mechanisms In The Tumor Microenvironment Using High-Dimensional Analyses, Swetha Anandhan

Dissertations and Theses (Open Access)

The advent of immune checkpoint therapy (ICT) has transformed cancer treatment, but its effectiveness is limited in certain cancers like pancreatic ductal adenocarcinoma (PDAC), which exhibit resistance to this therapy. To overcome this challenge, it is crucial to understand the underlying mechanisms that determine tumor response to ICT and develop rational therapeutic combinations. The tumor microenvironment (TME), including suppressive myeloid cells, regulatory T cells (Tregs), and cancer-associated fibroblasts (CAFs), plays a pivotal role in ICT responses. Leveraging single-cell technologies, this study explores the role and function of immune subsets in the TME that induce therapy resistance.

Using single-cell RNA sequencing …

Preclinical Evaluation Of Immunomodulatory Effects Of Aurora Kinase Inhibition In Human Papillomavirus Positive Cancers, Pragya Sinha

Dissertations and Theses (Open Access)

Human papillomavirus (HPV) is the causative agent of cervical cancer and some cancers of the penis, vulva, vagina, anus, and oropharynx. Current therapies for these cancers include a combination of surgery, radiotherapy, and chemotherapy that often results in permanent, life altering adverse effects. Immunotherapy is partially effective, but with significant recurrence and lower long-term survival. Importantly, there are no few biomarker-selective targeted therapies for these cancers. To address this unmet need, our collaborators conducted a large-scale drug screen and identified Aurora Kinase (AK) inhibitors as a unique class of reagents to induce selective apoptosis in HPV+, but not HPV- human …

The Regulation Of Autoimmunity Genes In Pancreatic Β-Cells By Nf-Κb, Thomas Malone Martin

LSU Doctoral Dissertations

Type 1 diabetes (T1D) is an autoimmune disease where the immune system targets the pancreatic islet beta-cells, which are responsible for insulin production and secretion, leading to a state of insulin insufficiency. Many of the molecular details of disease onset and progression remain poorly understood, including key aspects of cytokine signaling. Therefore, we have examined some of the consequences of inflammatory cytokine signaling as a critical module relevant to T1D. Using interleukin-1 (IL-1) signaling as a well-defined paradigm for inflammation, we investigated key components of this signaling pathway in pancreatic beta-cells. We identified ICAM-1, one of the proteins expressed in …

Mirna-489 Induces Immunogenic Cell Death In Triple Negative Breast Cancer Cells, Ryan P. Titus

Senior Theses

It has been well established that microRNAs (miRNAs) play an important role in the regulation of gene expression and consequently promoting or downregulating molecular pathways. When dysregulated, miRNAs have been found to serve as important biomarkers for cancer diagnosis and influence tumor initiation and progression. It has been previously established that miRNA-489 is a tumor suppressor microRNA, and it directly targets cell proliferative pathways like the HER2-SHP2-MAPK pathway. In this study, we focus on the role of miRNA-489, in the induction of immunogenic cell death (ICD) in triple-negative breast cancer cell lines. We first examined the effects of miRNA-489 on …

A Novel Therapeutic Approach To Regulate Carex8 Protein Expression Through E6-Conjugated Cell Penetrating Peptides, Jared D. Compaleo

Browse all Theses and Dissertations

Adenovirus is a human pathogen that causes cold like symptoms in healthy individuals, which could be lethal in pediatrics and the immunocompromised. In polarized epithelia, adenovirus uses the eight-exon isoform of the Coxsackievirus and Adenovirus Receptor (CAREx8) on the apical surface, to facilitate infection. CAREx8 protein expression level is regulated by the scaffolding protein MAGI-1, using two of its PSD95/Dlg-1/ZO-1 (PDZ) domains: PDZ2 and PDZ4. We previously showed that CAREx8 is degraded after interaction with PDZ4 and rescued following interaction with PDZ2. We then developed a PDZ2 binding decoy molecule (E6) that blocks the interaction between CAREx8 and PDZ2, which …

Environmental Toxicants And Human B Cells: Insights From Crispr Editing And Genomic Sequencing, Clayton Allex-Buckner

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The human immunoglobulin heavy chain gene locus (IGH) has two 3 prime regulatory regions (3’IGHRR), each containing three enhancers (hs3, hs1.2, hs4). In animal models, the 3’IghRR regulates IgH expression and class switch recombination (CSR) to different Ig isotypes. The 3’IGHRR hs1.2 enhancer in humans is polymorphic in that an invariant sequence (IS) can be repeated one to four times in tandem. The hs1.2 polymorphism is of interest due to its association with several human autoimmune disorders and its potential sensitivity to exogenous substances such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD or dioxin). In mouse models, TCDD inhibits the hs1.2 enhancer and 3’IghRR …

Cluster Homolog Of Immunoglobulin-Like Receptor Genes In Chicken Immune Responses, Brandi A. Sparling

Graduate Theses, Dissertations, and Problem Reports (ETD)

This dissertation explores the identity and role of immunoglobulin-like (Ig-like) receptors in chickens, with focus on their implications in disease and disease progression. These receptors, wisely expressed across immune cells, interact with the major histocompatibility complex (MHC) class I molecules to modulate immune responses in mammals. Due to the insufficient representation of chicken Ig-like receptors in online databases, this study systematically annotates the chicken Cluster Homolog of Immunoglobulin-like Receptors (CHIR) genes using advanced bioinformatic techniques, aligning with the release of the 7th edition of the chicken genome assembly that comprises builds for a broiler and layer chicken. The analysis identifies …

Lactobacillus Metabolite Nc As An Inflammation Inhibitor, Drew Hahnnah Landrowski

Master's Theses

The human body contains a diverse ecosystem of microbes. Commensal bacteria have numerous mutually-beneficial relationships with their host. Not only do they assist in digestion and gut homeostasis, they are critical for development and function of the immune system. As such, hosts and microbes alike have evolved mechanisms to foster symbiosis. Gut barrier function, toll-like receptor signaling, and metabolites are all examples of how hosts interact with microbes to promote this mutually-beneficial relationship. Metabolites from commensal bacteria promote the generation of regulatory T-cells, capable of ameliorating inflammation. A number of inflammatory, allergic, and autoimmune conditions are associated with dysbiosis. Therefore, …

Unraveling The Anti-Inflammatory Mechanisms And Efficacy Of Cannabidiol On The Progression Of A Murine Model Of Multiple Sclerosis From The Innate To The Adaptive Immune System To Clinical Symptoms, Christa Marie Frodella

Theses and Dissertations

Cannabidiol (CBD), a non-psychotropic phytocannabinoid with structural similarity to Δ 9 -tetrahydrocannabinol (THC), is currently being investigated as a therapeutic for its immunosuppressive effects. One disease for which CBD is extensively researched is multiple sclerosis (MS), a demyelinating, autoimmune disorder, and its murine model counterpart, experimental autoimmune encephalomyelitis (EAE). The focus of this dissertation aimed to analyze the transcriptomic brain pathways in EAE and its comparison to MS in addition to CBD’s immunosuppressive mechanisms in the innate and adaptive immune systems. Evidence presented here showed that transcriptomic signaling pathways in the EAE brain of mice with clinical symptoms were similar …

A Study Of Multiple Sclerosis, Christine Chen

The Cardinal Edge

No abstract provided.

Investigating Host Defenses Of North American Salamanders Against The Recently Emerged Chytrid Pathogen, Batrachochytrium Salamandrivorans, Kenzie Pereira

Electronic Theses and Dissertations

A recently emerged chytrid fungal pathogen, Batrachochytrium salamandrivorans (Bsal) threatens salamander biodiversity. Bsal susceptibility varies between and within salamander species, but little is known about the mechanisms underlying these differences. Susceptibility is likely influenced by numerous interacting factors, but my dissertation studied the role of host immune responses.

My first aim investigated between species differences by studying the bioactive properties of salamander skin peptides against Bsal and the related pathogen, B. dendrobatidis (Bd). Skin peptides were collected from five salamander species, used for in vitro assays, and analyzed by RP-HPLC. While skin peptides from one …

A Microfluidics-Based Approach For Isolation Of Antigen-Specific Cd8+ T Cells, Meredith Frank

Dissertations and Theses (Open Access)

Cancer is a global epidemic: there are predicted to be 200 million new cases this year alone. Almost a quarter of all cancer-related deaths are caused by lung cancer, for which 5-year survival rates are just above 20%. 85% of lung cancer diagnoses are classified as non-small cell lung cancer (NSCLC) for which 5-year survival rates in metastatic disease are less than 10%. Early detection and targeted therapies have improved prognoses, yet relapse is still common among patients.

Immunotherapies that leverage tumor-specific CD8⁺ cytotoxic T cells have shown great promise for the treatment of NSCLC. However, although highly promising, …

Exploiting 4–1bb Immune Checkpoint To Enhance The Efficacy Of Oncolytic Virotherapy For Diffuse Intrinsic Pontine Gliomas, Virginia Laspidea, Montserrat Puigdelloses, Sara Labiano, Lucía Marrodán, Marc Garcia-Moure, Marta Zalacain, Marisol Gonzalez-Huarriz, Naiara Martínez-Vélez, Iker Ausejo-Mauleon, Daniel De La Nava, Guillermo Herrador-Cañete, Javier Marco-Sanz, Elisabeth Guruceaga, Carlos E De Andrea, María Villalba, Oren Becher, Massimo Squatrito, Verónica Matía, Jaime Gállego Pérez-Larraya, Ana Patiño-García, Sumit Gupta, Candelaria Gomez-Manzano, Juan Fueyo, Marta M Alonso

Faculty, Staff and Student Publications

Diffuse intrinsic pontine gliomas (DIPGs) are aggressive pediatric brain tumors, and patient survival has not changed despite many therapeutic efforts, emphasizing the urgent need for effective treatments. Here, we evaluated the anti-DIPG effect of the oncolytic adenovirus Delta-24-ACT, which was engineered to express the costimulatory ligand 4-1BBL to potentiate the antitumor immune response of the virus. Delta-24-ACT induced the expression of functional 4-1BBL on the membranes of infected DIPG cells, which enhanced the costimulation of CD8+ T lymphocytes. In vivo, Delta-24-ACT treatment of murine DIPG orthotopic tumors significantly improved the survival of treated mice, leading to long-term survivors that developed …

Feasibility Of Tubulin As A Control For Gene Expression Following Transfection In Mouse Monocyte/Macrophage-Like Cells, Ankita Chabra

Honors Program Theses and Research Projects

Transfection, which is the ability to modify host cells’ genetic content, has broad application in studying normal cellular processes, molecular mechanism of disease and gene therapy. There are several transfection techniques, and all require either a control or a reference gene. Commonly used controls for transfection experiments are housekeeping genes, which maintain expression for a given cell/tissue, experimental conditions, and treatment. However, recent research has uncovered that expression levels of housekeeping genes may vary depending on the gene, cell type and experimental conditions. A growing body of evidence demonstrates that housekeeping genes are inadequate internal standards for measuring gene expression …

Evaluation Of Oasl And Herc5’S Role In The Non-Lytic Clearance Of Influenza A Virus From Club Cells, Steve Crisafulli

West Chester University Master’s Theses

Influenza A virus (IAV) is a highly infectious pathogen responsible for causing severe respiratory illness and death in humans and animals worldwide. Due to highly effective strategies to negate host antiviral defenses, IAV leads to the death of nearly all infected cells. Furthermore, IAV induces high levels of genome-damaging oxidative stress within infected cells and suppresses the cellular mismatch repair (MMR) mechanism, thereby inhibiting expression of key antiviral genes, which further contributes to cell death. However, recent studies have demonstrated that a subset of respiratory epithelial cells, called club cells, are able to non-lytically clear IAV and continue to survive …

Ifn-Γ Increases The Expression Of Sars-Cov-2 Receptors On Vero E6 Cells, Bindu Madhavi Madabattula

Browse all Theses and Dissertations

Respiratory epithelial cells are the initial target for SARS-CoV-2 infection. IFN-γ is known to increase the expression of ACE-2, an initial receptor for SARS-CoV-2, on epithelial cells. This study focuses on examining the effect of IFN-γ for ACE-2, TMPRSS2, and neuropilin-1 on Vero E6 cells using two immunofluorescence methods, namely, direct (membrane) fluorescence method and Cytation5 method. Direct fluorescence was determined using an Accu-Scope and ImageJ analysis. Using this method, significance (p<0.023) was observed only for ACE-2 when Vero E6 cells were treated with IFN-γ. Cytation5 fluorescence was determined using a Bio-tek Cytation5 plate reader. The results showed that IFN-γ significantly increased (p<0.001) the expression of ACE-2, neuropilin-1, and TMPRSS2. These results indicate Cytation5 is a more sensitive method for determining the expression of receptors on Vero E6 cells. The elevated levels of SARS-CoV-2 receptors expression resulting from IFN-γ treatment makes the epithelial cells more susceptible targets of SARS-CoV-2 infection. IFN-γ is most likely provided by innate immune cells in the initial COVID-19 infection, consequently contributing to the severity of disease.

Expression Of Sars Cov2 Receptors Influenced Upon Cytokine Polarizations (Il-4 And Ifnγ) In Hemangioendothelioma Cells, Chandra Lekha Koopari

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Endothelial cells are distinct multifunctional cells with essential metabolic and synthetic roles along with their ability to function as selective permeability barrier. Endothelial cells (ECs), the major component of blood vessels, essentially interact directly yet differently with inflammatory cytokines. ECs are well recognized to be polarized cells, but little is known about the potential function of inflammatory mediators. Covid 19 may have long-term health effects on par with chronic illnesses. Vascular inflammatory disease and coagulopathy linked to COVID-19 are exacerbated by endothelial cell (EC) dysfunction. SARS-CoV-2 enters the host cell through the Angiotensin Converting Enzyme 2 (ACE2) receptor and primes …

Immunological Factors Associated With Siv/ Shiv Persistence In Diverse Tissue Niches, Omalla A. Olwenyi

Theses & Dissertations

The significant challenge towards a successful HIV cure lies in eradicating persistent viral reservoirs across diverse tissue niches. As a result, HIV-infected individuals have to resort to lifelong antiretroviral therapy. Recent news of supposed HIV eradication in a second patient has further re-invigorated the fields of HIV cure. However, a few barriers remain, such as the lack of currently available assays to accurately quantify viral reservoirs, limited information on cellular factors associated with persistence, and varied dynamics of the viral reservoir in various body compartments. Lastly, HIV-infected individuals live different lifestyles stemming from comorbid substance abuse including consumption of morphine, …

Intranasal Hpv Peptide Vaccine Formulation Induces Potent Cytotoxic Cd8 T Cell Immunity For The Treatment Of Genital Hpv Tumors, Gloria Sierra

Dissertations and Theses (Open Access)

Human Papillomavirus (HPV) induced cancers continue to affect millions of women worldwide, with the five year survival rate hovering just under 60% in some demographics. Therefore there is an unmet need to develop effective, yet, easily administered therapies to treat established HPV genital lesions. Even though immune checkpoint therapy (ICT) is a promising treatment option in some HPV+ cancers, the high cost and associated toxicities are still major concerns for their widespread application. HPV cancers are textbook candidates for therapeutic vaccination intervention because they’re driven by the expression of viral oncoproteins E6 and E7, which serve as ideal tumor specific …

An Investigation Of Healthcare Supports For Those With Food Allergy In Ireland, Joseph Bolger, Nicola Blake, Sneha Vinod

International Undergraduate Journal of Health Sciences

Introduction: In Ireland, around 5% of children and 3% adults have food allergy (134,000 people). This current paper describes a survey that was carried out on a subset of service-users with the aim of identifying whether there is a need for increased specialist medical services and/or for a funded charity such as Anaphylaxis Ireland, defunct since 2015.

Materials & Methods: These needs were assessed via an online survey using Google Forms. The survey was conducted from 17-27th February 2020. There were 31 questions in total, relating to topics such as symptoms, clinical wait times, satisfaction with care provided and demand …

Full Issue: The International Undergraduate Journal Of Health Sciences, Volume 1, Issue 1, June 2021, Iujhs Full Issue

International Undergraduate Journal of Health Sciences

The full June 2021 issue (Volume 1, Issue 1) of the International Undergraduate Journal of Health Sciences

Temperature-Dependent Macrophage Activity In Rainbow Trout, Danica Mcgrevey

Biological Sciences Undergraduate Honors Theses

Fever is an essential component of the immune response. Fever enhances immune responses as well as creates an environment in which the body has advantages over pathogens. Macrophages are often the first cells that come in contact with pathogens, as they reside in tissues. They are important for their engulfment of pathogens that results in the digestion of the pathogen, but they also produce nitric oxide and cytokines that contribute to immune response in a variety of ways, including initiating adaptive immunity and directing the production and activity of other immune cells. We were curious about macrophages from other temperature …

Unraveling Host-Gut Microbiota Dialogue And Its Impact On Response To Immune Checkpoint Blockade, Alexandria Cogdill

Dissertations and Theses (Open Access)

Cancer is a disease with only one degree of separation, affecting one in two men and one in three women in their lifetimes; accounting for 1 of every 6 deaths. While cancer mortality rates continue to improve, incidence rates are expected to rise and shift through 2050 due to epidemiological and demographic transitions worldwide. As such, it is imperative to continue to investigate and improve our understanding of both disease etiology and hallmarks of response to treatment. Currently, conventional therapies include, but are not limited to, surgery, chemotherapy, and radiotherapy. However, within the past decade, major advances have been made …

Antibodies Against Egf-Like Domains In Ixodes Scapularis Bm86 Orthologs Impact Tick Feeding And Survival Of Borrelia Burgdorferi, Juraj Koči, Sandhya Bista, Payal Chirania, Xiuli Yang, Chrysoula Kitsou, Vipin Singh Rana, Ozlem Buyuktanir Yas, Daniel E. Sonenshine, Utpal Pal

Biological Sciences Faculty Publications

Ixodes scapularis ticks transmit multiple pathogens, including Borrelia burgdorferi sensu stricto, and encode many proteins harboring epidermal growth factor (EGF)-like domains. We show that I. scapularis produces multiple orthologs for Bm86, a widely studied tick gut protein considered as a target of an anti-tick vaccine, herein termed as Is86. We show that Is86 antigens feature at least three identifiable regions harboring EGF-like domains (termed as EGF-1, EGF-2, and EGF-3) and are differentially upregulated during B. burgdorferi infection. Although the RNA interference-mediated knockdown of Is86 genes did not show any influences on tick engorgement or B. burgdorferi sensu stricto persistence, the …

Il-10 And Tgf-Beta Increase Connexin-43 Expression And Membrane Potential Of Hl-1 Cardiomyocytes Coupled With Raw 264.7 Macrophages, Cora B. Cox

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Cardiomyocytes and macrophages have been found to interact via connexin-43 hemichannels. The role of connexin-43, however, is not fully understood. This study shows that these interactions aid in increasing the membrane potential of cardiomyocytes allowing contraction of the cells. HL-1 cardiomyocytes and RAW 264.7 macrophages in coculture increased expression of connexin-43 compared to cardiomyocytes alone. Co-cultures also increased the fluorescence of Di-8-ANEPPS potentiometric dye indicating an increase in cardiomyocyte membrane potential. Treatment with IL-10 and TGF-beta further increased connexin-43 expression and membrane potential. Treatment with SOCS3 inhibited the effects of TGF-beta and IL-10 while having no effect on its own. …

Pushing The Limits: Increasing The Speed And Specificity Of Sars-Cov-2 Testing, Grayson Way

Theses and Dissertations

The prevalence and spread of the current COVID-19 pandemic have highlighted the importance of continual improvements upon current microbiological testing methods. Rapid and accurate testing can help mitigate spread by improving on the time to quarantine and quarantine duration required. As of the writing of this thesis, COVID-19 has been responsible for more than 500,000 deaths in the United States of America, and greater than 2 million deaths globally. The work done in this thesis has shown improvements in the current SARS-CoV-2 testing methodology by reducing the time it takes for patient testing while maintaining accuracy and the sensitivity required …