Immunology of Infectious Disease Commons^™

Alteration Of The Interferon Alpha Signaling Pathway Significantly Affects Alzheimer's Disease Pathology In App/Ps1 Mouse Model., Ranjit Kumar Das, Nirakar Sahoo, Chun Xu, Hansapani Rodrigo, Michael Paul Murphy, Upal Roy, Deepa Roy

Research Symposium

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive impairment, memory loss, and disturbances in behavior. The exact cause of the disease is unknown but there is evidence of molecular pathways alteration within the brain. Many molecular mechanisms have been studied for the progression of AD. Nonetheless, the contribution of the signal transducer and activator of transcription 1 (STAT1) and interferon-induced protein with tetratricopeptide repeats 3 (IFIT3) genes have not been well established in AD pathology. This study aimed to investigate the contribution of STAT1 and IFIT3 in the BALB/C and APP/PS1 mouse models. We analyzed the STAT1 …

Sars-Cov-2: Tale Of A Microscopic Murderer, Josiah P. Garner

Quest

Independent Study

Research in progress for BIOL1406: Biology for Science Majors I

Faculty Mentor: Amina Tassa, Ph.D.

I am delighted to introduce Josiah Garner’s “SARS-CoV-2: Tale of a Microscopic Murderer.” This independent study assignment explores the impact of a novel, deadly, and worldwide virus. The assignment also examines the fast development of vaccines to control the spread and reduce the symptoms of the virus.

Josiah’s paper focuses on the early history of the emergence of COVID-19, the world response, and vaccine development. He demonstrates critical thinking skills and effectively utilizes various research methods to obtain and communicate his information. Josiah …

Elucidating The Biomechanics Of Mertk-Mediated Efferocytosis, Brandon Hayato Dickson

Electronic Thesis and Dissertation Repository

Macrophages are key mediators of efferocytosis – the phagocytic engulfment and removal of apoptotic cells. During engulfment, the coordinated activity of efferocytic receptors induces the remodeling of the actin cytoskeleton, which facilitates the envelopment of the cell by the plasma membrane. Mer receptor tyrosine kinase (MERTK) is a crucial efferocytic receptor, but its role during actin remodeling is not well understood. Previously, our lab showed that MERTK is an activator of β₂ integrins – which are comprised of receptors known to induce the actin polymerization that is required for engulfment. We hypothesized that MERTK is an indirect stimulator of …

Osteoimmunology And The Reconstruction Of Host Immunological Status In Treponemal Infection: Effect Of Activated Immune Cells By Oral Pathogens And Treponema Pallidum On Osteoclastogenesis., Michayla Gatsos

College of Arts & Sciences Senior Honors Theses

Syphilitic infection caused by bacterium Treponema pallidum pallidum (Tp) offers an excellent model to study the long-lasting interplay between the immune and skeletal systems and could be used to reconstruct host immunological status. We propose that a hyper-inflammatory phenotype developed during acquired syphilis will have a systemic impact on most bone microenvironments involving inflammatory processes, such as the one developed in periodontal disease (PD). Using osteoimmunological in vitro protocols, we explore whether immune activation by Tp antigens and PD pathogens can impact osteoclastogenesis (OCG), ultimately helping to understand the bone alterations caused by systemic inflammatory processes in skeletal material. We …

Immunomodulatory Effects Of Resolvin D2 In A Model Of Infection, Prem Yugandhar Kadiyam Sundarasivarao

Graduate School of Biomedical Sciences Theses and Dissertations

Dysregulated hyperinflammatory host immune response to underlying bacterial infections is a characteristic of sepsis. In sepsis, bacteria often trigger abnormal hyperinflammatory responses which can cause multiple organ failure and if sustained can lead to an immunosuppressive phase where the host is susceptible to secondary infections caused by opportunistic bacteria like Pseudomonas aeruginosa (P. aeruginosa). In our studies, we used a 2-hit model of cecal ligation and puncture (CLP) followed by P. aeruginosa secondary lung infection to investigate cellular and molecular mechanisms in the beneficial action of resolvin D2 (RvD2). Resolvins of the D-series are a group of fatty acids known …

Investigating The Roles Of Lung Epithelial Stat3 In Therapeutically Inducible Resistance To Acute Bacterial Pneumonia., Vikram V. Kulkarni, Vikram V. Kulkarni

Dissertations & Theses (Open Access)

Investigating the roles of lung epithelial STAT3 in therapeutically inducible resistance to acute bacterial pneumonia.

Vikram Vitthal Kulkarni, M.S.

Advisory Professor: Scott Evans, MD.

The lung epithelium is a dynamic tissue capable of displaying structural and functional plasticity in response to pathogenic challenges. Our lab has demonstrated that it is possible to therapeutically exploit the lung epithelium’s versatility by inducing resistance to lethal pneumonias caused by viruses, bacteria and fungi. An inhaled combination of a TLR2/6 agonist and a TLR9 agonist (Pam2ODN) results in robust protection against otherwise lethal pneumonia caused by Pseudomonas aeruginosa. Pam2ODN-mediated protection requires key signaling …

Sex Differences In Host Resistance And Tolerance To The Common Avian Pathogen Mycoplasma Gallisepticum, Chloe Connelly

Biological Sciences Undergraduate Honors Theses

As we face the threat of global pandemics, one thing becomes clear: biological research is not just about the pursuit of the unknown, but about protecting our future. Understanding disease transmission and predicting pathogen epidemics is more important than ever. Prior studies have indicated that in populations where one sex engages in more social behaviors and movement that sex may drive disease transmission. This supports sex as a factor to consider in the study of epidemic dynamics. Host physiology and immune strategies are another factor that can influence epidemics. Two commonly examined strategies are tolerance and resistance. Tolerance is the …

Comparative Characteristics Of Integrin Αdβ2 Binding To Native Fibrinogen And Fibrinogen Modified By Dha Oxidation During Inflammation, Ajibola Ilesanmi

Electronic Theses and Dissertations

2-ω-carboxyethylpyrrole (CEP) is a product of docosahexaenoic acid (DHA) oxidation, which forms covalent adducts with different proteins. CEP-modified proteins can interact with macrophage receptor, integrin αDβ2. This study aims to compare αDβ2 binding to its physiological ligand, fibrinogen, and CEP-modified fibrinogen, which is formed during inflammation. We hypothesize that modification of fibrinogen changes its ligand-binding properties to integrin αDβ2 which can affect macrophage migration and retention. Recombinant αD I-domain and αDβ2-transfected HEK293 cells were used for the experiments. Using biolayer interferometry, we found that the affinity of αD I-domain binding to fibrinogen-CEP was higher than fibrinogen and inhibited by the …

The Effects Of Specialized Pro-Resolving Mediator Lipoxin A4 On Pseudomonas Aeruginosa Biofilms And Interactions With Monocytes, Julianne M. Thornton

Graduate School of Biomedical Sciences Theses and Dissertations

Pseudomonas aeruginosa (P. aeruginosa) is an opportunistic pathogen known as a major cause of hospital-acquired secondary infections, commonly causing chronic respiratory infections in immunocompromised individuals, especially those with cystic fibrosis, and often found in wound infections. P. aeruginosa uses the quorum sensing pathway to readily form protective biofilms, which reduce the efficacy of antibiotics and access by host immune cells to eradicate the pathogen. Specialized pro-resolving mediators (SPMs) are lipids endogenously produced by the host immune response to infection to aid in infection resolution. One SPM, Lipoxin A4 (LxA4), has been shown to be a robust quorum sensing inhibitor.

The …

Prevalence Of Sars-Cov-2 Antibodies In Liberty University Student Population, Emily Bonus

Senior Honors Theses

In 2020, the virus SARS-CoV-2 gained attention as it spread around the world. Its antibodies are poorly understood, and little research focuses on those with few COVID-19 complications yet large numbers of close contacts: university students. This longitudinal study recorded SARS-CoV-2 antibody presence in 107 undergraduate Liberty University students twice during early 2021. After extensive data cleaning and the application of various statistical tests and ANOVAs, the data seems to show that in the case of COVID-19 infections, SARS-CoV-2 IgM antibodies are immediately produced, and then IgG antibodies follow later. However, the COVID-19 vaccine causes the production of both IgM …

Rna Virus-Mediated Changes In Organismal Oxygen Consumption Rate In Young And Old Drosophila Melanogaster Males, Eli Hagedorn, Dean Bunnell, Beate Henschel, Daniel Smith Jr, Stephanie Dickinson, Andrew Brown, Maria De Luca, Ashley Turner, Stanislava Chtarbanova

Research, Publications & Creative Work

Aging is accompanied by increased susceptibility to infections including with viral pathogens resulting in higher morbidity and mortality among the elderly. Significant changes in host metabolism can take place following virus infection. Efficient immune responses are energetically costly, and viruses divert host molecular resources to promote their own replication. Virus-induced metabolic reprogramming could impact infection outcomes, however, how this is affected by aging and impacts organismal survival remains poorly understood. RNA virus infection of Drosophila melanogaster with Flock House virus (FHV) is an effective model to study antiviral responses with age, where older flies die faster than younger flies due …

Human Milk: From Covid-19 Immunity To Breast Cancer Risk Assessment, Vignesh Narayanaswamy

Doctoral Dissertations

Breastmilk is a complex biological fluid containing macromolecules including lipids, oligosaccharides, proteins as well as several types of cells. Several studies have reported in detail of these components. My focus is studying the protein component of breastmilk, specifically antibodies, cytokines, and other secreted factors in the setting of different pathogenicity in women. Studies have demonstrated that the levels of numerous cytokines as well as the levels of pathogen-specific antibodies are altered in milk upon either maternal or infant infections. Additionally, there are reports that the levels of certain inflammatory markers are altered in milk among women with breast cancer or …

The Immune Modulation On Innate Immunity, From Pathogen Recognition To Fungal Clearance., Ko-Wei Liu

Dartmouth College Ph.D Dissertations

The human lung is not sterile but a complex environment with various microorganisms. Besides commensals in the lung, hundreds to thousands of individual microbiomes enter the lung every day but without causing the symptom. Host innate immunity plays an important role in maintaining homeostasis of the lung environment and as the first defense line against pathogens. Aspergillus fumigatus (A. fumigatus) is a saprophytic filamentous fungus that can cause human disease in immune compromised patients. However, with functional innate immunity, immune cells can quickly recognize pathogen associated molecular patterns (PAMPs) from A. fumigatus through pattern recognition receptors (PRRs). The activation of …

Antibody-Dependent Enhancement Activity Of A Plant-Made Vaccine Against West Nile Virus, Amber M. Paul, Haiyan Sun, Dhiraj Acharya, Huafang Lai, Junyun He, Fengwei Bai, Qiang Chen

Publications

West Nile virus (WNV) causes annual outbreaks globally and is the leading cause of mosquito-borne disease in Unite States. In the absence of licensed therapeutics, there is an urgent need to develop effective and safe human vaccines against WNV. One of the major safety concerns for WNV vaccine development is the risk of increasing infection by related flaviviruses in vaccinated subjects via antibody-dependent enhancement of infection (ADE). Herein, we report the development of a plant-based vaccine candidate that provides protective immunity against a lethal WNV challenge mice, while minimizes the risk of ADE for infection by Zika (ZIKV) and dengue …

Generation Of Chimeric Rhinoviruses Presenting Sars-Cov-2 Broadly Neutralizing Epitopes And Their Antigenicity Characterization, Danish Ansari

Biotechnology Theses

The global COVID pandemic is not yet fully under control as there were over 21 million new cases of SARS-CoV-2 infections and over 50,000 deaths globally as of January of 2022. A heavily mutated variant of concern, Omicron is responsible for most of these cases which demands an urgency for a new vaccine. NIH reports over 180 vaccine candidates that use various strategies currently in development. However, a recurring concern with these vaccines is that the continuous viral mutations decrease the efficacy of vaccines. Therefore, we proposed to construct a human rhinovirus (HRV) based chimeric virus containing highly conserved, broadly …

The Psychology Of Science Denialism And Lessons For Public Health Authorities, Brenna Moreno, Molly J. Walker Wilson

All Faculty Scholarship

As it wreaked tragedy on the world, the outbreak of COVID-19 helped expose a pandemic of a different kind, one steeped in distrust and contrarianism. This movement, termed science denialism, has been lurking and undermining public health efforts for decades. Specifically, it is “the employment of rhetorical arguments to give the appearance of legitimate debate where there is none, an approach that has the ultimate goal of rejecting a proposition on which a scientific consensus exists.” Unlike skepticism, which is “doubt as to the truth of something” and works to progress both science and society, denialism is characterized by individuals’ …

Proposing An Rna Interference (Rnai)-Based Treatment For Human Immunodeficiency Virus (Hiv) By Analyzing The Post-Transcriptional Gene Targeting Of Sars-Cov-2, Hepatitis C Virus, And A549 Lung Cancer Cells, Arjun Jagdeesh

Undergraduate Research Posters

Human Immunodeficiency Virus (HIV) is a retrovirus that infects CD4+ T cell lymphocytes in humans, leading to the development of Acquired Immunodeficiency Syndrome (AIDS) if left untreated. While current treatment methods, including antiretroviral combination treatments, effectively limit HIV replication, HIV can evade these treatments due to its high mutation rate. Long-term antiretroviral treatment can also be toxic to patients, meaning patients would benefit from a new mechanism of HIV treatment. RNA interference (RNAi) is an antiviral pathway found in mammals, plants, and insects that involves a small-interfering RNA that is incorporated into a protein complex called the RNA-induced Silencing Complex …

The Covid-19 Pandemic And Its Influence On The Human Immune System, Nicole L. Riha

Undergraduate Honors Theses

COVID-19 rapidly infected the world, and scientists continue to research how the disease spread and killed as many as it did by analyzing how it affects the human immune system and referring to past pandemics. Since the pandemic is ongoing, scientists do not fully understand how the virus works and if lockdowns were effective. Nevertheless, a discussion on what is known about COVID-19's influence on the human immune system is needed. With an understanding of the COVID-19 pandemic, scientists can make more effective treatments for COVID-19 and learn how to manage future pandemics.

Investigating The Pi3k/Akt/Atm Pathway, Telomeric Dna Damage, T Cell Death, And Crispr/Cas9-Mediated Gene Editing During Acute And Chronic Hiv Infection, Sushant Khanal

Electronic Theses and Dissertations

Human Immunodeficiency Virus (HIV) infection initiates major metabolic and cell- survival complications. Anti-retroviral therapy (ART) is the current approach to suppress active HIV replication to a level of undetected viral load, but it is not a curative approach. Newer and sophisticated gene editing technologies could indeed be a potent antiviral therapy to achieve a clinical sterilization/cure of HIV infection. Chronic HIV patients, even under a successful ART regimen, exhibit a low-grade inflammation, immune senescence, premature aging, telomeric DNA attrition, T cell apoptosis, and cellular homeostasis. In this dissertation, we investigated CD4 T cell homeostasis, degree of T cell apoptosis, an …

Optimization Of Clostridium Septicum Antigen Production And Evaluation Of Vaccine Administration Parameters For A Candidate Bacterin-Toxoid To Prevent Dermatitis In Commercial Turkeys, Aaron Forga

Graduate Theses and Dissertations

The objective of this thesis was to optimize the hemolytic activity of two isolates of Clostridium septicum to evaluate if hemolytic titer of C. septicum antigen at time of formalin inactivation corresponded to increased serum antibody titer to the C. septicum alpha-toxin of turkeys immunized with an experimental formalin inactivated bacterin-toxoid vaccine. Chapter 1 provides a brief overview of the thesis. Chapter 2 consists of a literature review focused on clostridial dermatitis, specifically C. septicum-associated dermatitis (cellulitis) that affects commercial turkeys. Chapter 3 outlines our attempts to optimize an experimental autogenous bacterin-toxoid vaccine as a potential strategy to mitigate clostridial …