Immunology of Infectious Disease Commons^™

Pseudomonas Aeruginosa Vaccine Development Using Dual-Species Whole Cell And Subunit Vaccines, Catherine Bell Blackwood

Graduate Theses, Dissertations, and Problem Reports (ETD)

Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen which can cause severe, recurrent, and chronic infections. The pathogen is highly adaptable, and pneumonia caused by it is associated with high morbidity and mortality, especially in individuals with the genetic disorder cystic fibrosis. Antibiotic resistance amongst clinical isolates of P. aeruginosa is steadily increasing, and multi-drug resistant strains are prevalent. There is currently no vaccine available for commercial use against P. aeruginosa. For these reasons, we sought to understand the immunity to P. aeruginosa induced by whole cell vaccination and identify antigens for development of future subunit vaccines. In this dissertation, …

Targeting The Cerebrovasculature In Sepsis: A Focus On The Brain Microvascular Endothelium, Divine C. Nwafor

Graduate Theses, Dissertations, and Problem Reports (ETD)

The blood-brain barrier (BBB) is a critical interface between the systemic circulation and the brain. It is a specialized multicellular unit composed of brain microvascular endothelial cells (BMECs), pericytes, a basement membrane, and astrocytic end foot processes. BMECs are a principal component of the BBB that provide the structural framework needed for the stringent transport of molecules into the brain. BMEC dysfunction permits the trafficking of neurotoxins from systemic circulation into the brain, which ultimately exacerbates BBB dysfunction and neuroinflammation. Studies have shown that BBB dysfunction is a key determinant of cognitive decline in sepsis. However, there are critical knowledge …

Transcriptional Regulation Of Duox-Dependent Reactive Oxygen Species Production Against Bacterial Infection In The Gut Of Cat Fleas (Ctenocephalides Felis)., Ryne W. Maness

College of Graduate Studies: Theses & Dissertations

Fleas (Order Siphonaptera) are opportunistic blood feeders that parasitize a wide variety of mammals and birds. They also transmit bacterial pathogens that cause diseases in humans (e.g., murine typhus, flea-borne spotted fever, cat scratch disease, and plague). Because they acquire infectious pathogens while blood feeding, the flea gut is considered to be the initial site of infection. While immune responses have been well documented in other disease vectors, few studies have identified the immune mechanisms involved in defense of the flea gut. In other hematophagous insects, the synthesis of reactive oxygen species (ROS) is the immediate immune defense mechanism against …

Multistrain Hiv-1 Elimination: A Crispr-Cas9 And Theranostics-Based Approach, Jonathan Herskovitz

Theses & Dissertations

A critical barrier to achieving a functional cure for infection by human immunodeficiency virus type one (HIV-1) rests in the presence of latent proviral DNA integrated in the nuclei of host CD4+ T cells and mononuclear phagocytes. Accordingly, HIV-1-infected patients must adhere to lifelong regimens of antiretroviral therapy (ART) to prevent viral rebound, CD4+ T cell decline, and progression to acquired immunodeficiency syndrome (AIDS). Gene editing using clustered regularly interspersed short palindromic repeat (CRISPR)-Cas9 technology stands as one means to inactivate integrated proviral DNA. We devised a mosaic gRNA CRISPR-Cas9 system- TatDE- that targets viral transcriptional regulator genes tat / …

Impact Of Endangered Animal Protection Rights, Policies, And Practices On Zoonotic Disease Spread, Daniella Fedak-Lengel

Honors Projects

Building on field research in Costa Rica and Belize, this honors project analyzes environmental and endangered animal protection policies, rights, and practices in Central America and the Caribbean, and assesses the impact of veterinary science and biological research and practice, particularly conservation biology, on animal welfare concerns. Informed by the recent surge in awareness regarding zoonoses and zoonotic disease transmission, prevention and control, resulting from the current global pandemic of SARS-CoV-2, the project assesses the need for new and innovative types of collaboration, particularly involving conservation biologists, environmental scientists, public health experts, law and policy makers, and global trade and …

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 …

Immune Activation Induces Telomeric Dna Damage, Reduces Memory Precursors, And Promotes Short-Lived Effector T Cell Differentiation In Chronic Hcv Infection, Lam Nguyen

Electronic Theses and Dissertations

Chronic hepatitis C virus (HCV) infection exhibits persistent high viral load, inducing T cells differentiation and dysfunction in chronically infected individuals. Recent longitude studies in both HCV specific- and bulk T cells reveal that chronic immune stimulation is the driving force for the impaired T cell functions, however, the underlying mechanisms remain elusive. Here, we show that peripheral CD4⁺ T cells from chronically HCV-infected patients exhibit lymphopenia with the reduction of naïve population and expansion of effector memory T cells. CD4⁺ T cells from HCV patient also display elevated activation markers. including HLA-DR, GLUT1, Granzyme B, and short-lived …

Malaria, Microbes, And Mice: The Role Of The Gut Microbiota On The Immune Response To Plasmodium Infection And The Treatment Potential Of Microbiota Modulation., Morgan L. Waide

Electronic Theses and Dissertations

Plasmodium infection leads to over 200 million cases of malaria and 400,000 deaths worldwide each year. These deaths are largely in children under the age of five and pregnant women [1]. Caused by transmission of Plasmodium parasites by the female Anopheles mosquito, malaria poses a risk for over 40 percent of the world’s population [1]. Despite worldwide efforts to eradicate malaria leading to a decrease in malaria-associated mortalities in the early 2000s [2], growing resistance to the available antimalarials and the lack of an effective, long-lasting vaccine has caused this decrease to plateau in recent years [1, 3-6]. Furthermore, malaria …

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 …

The Effect Of Fcgammariia Polymorphisms On Dengue Outbreak Severity, Leah Darwin, Richard V. Clarke

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

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 …

Mesenchymal Stem Cells And Their Extracellular Vesicles: A Potential Game Changer For The Covid-19 Crisis, Dina H. Kassem, Mohamed M. Kamal

Pharmacy

Corona virus disease 2019 (COVID-19) is a global public health crisis. The high infectivity of the disease even from non-symptomatic infected patients, together with the lack of a definitive cure or preventive measures are all responsible for disease outbreak. The severity of COVID-19 seems to be mostly dependent on the patients’ own immune response. The over-activation of the immune system in an attempt to kill the virus, can cause a “cytokine storm” which in turn can induce acute respiratory distress syndrome (ARDS), as well as multi-organ damage, and ultimately may lead to death. Thus, harnessing the immunomodulatory properties of mesenchymal …

Next Generation Aryl Hydantoins As Antischistosomal Agents, Derek A. Leas

Theses & Dissertations

Schistosomiasis, also known as “snail fever,” is both an acute and chronic disease spread by trematode flukes from the tropical parasitic worm genus Schistosoma. The flukes are spread via diseased freshwater snails, which release the parasites into the water column where they find a new human host. According to the World Health Organization (WHO), 99 million people were treated for schistosomiasis in 2017. The primary treatment used to combat schistosomiasis is the drug praziquantel (PZQ), but due to high drug pressure and widespread administration, its effectiveness has eroded because of rising drug resistance. Furthermore, PZQ is active against adult but …

The Investigation Of Surface Structures On Various Pathogens And Their Interactions With The Human Immune System, Carmen M. Villalobos

Biomedical Engineering ETDs

The cell surface is the first interface the host immune system encounters and

its investigation has led to a better understanding of cellular biology and types of

pathways that pathogens target in a host cell. The cell surface has evolved to include

many functions such as manipulation of the cytoskeleton, cell signaling, membrane

trafficking, adhesion, and integration into host tissue. The pathogens of interest are

the pathogenic fungus, Candida albicans, and the parasite, Giardia lamblia and we

investigate the consequences of drug treatments on the cell surface, leading to

promising new targets.

Plasmodium Impairs Antibacterial Innate Immunity To Systemic Infections In Part Through Hemozoin-Bound Bioactive Molecules., Christopher Lynn Harding

Electronic Theses and Dissertations

Despite efforts to decrease the global health burden of malaria, infections with Plasmodium species continue to cause over 200 million episodes of malaria each year which resulted in 405,000 deaths in 2018 [1]. One complication of malaria is increased susceptibility to invasive bacterial infections. Plasmodium infections impair host immunity to non-Typhoid Salmonella (NTS) through activities of heme oxygenase I (HO-I) )-induced release of immature granulocytes and myeloid cell-derived IL-10. Yet, it is not known if these mechanisms are specific to NTS. We show here, that Plasmodium yoelii 17XNL (Py) infected mice had impaired clearance of systemic Listeria monocytogenes (Lm) during …

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 …

Roles Of Endothelial Cell Heat Shock Protein A12b And Β-Glucan, A Reagent For Trained Immunity In The Regulation Of Inflammation In Sepsis, Fei Tu

Electronic Theses and Dissertations

Sepsis is dysregulated host immune response to infection causing life-threatening organ dysfunction. Endothelial cell dysfunction and uncontrolled inflammatory responses are two contributors for sepsis-induced mortality. The crosstalk between endothelial and immune cells plays a critical role in the pathophysiology of sepsis. Therefore, understanding the mechanism of interaction between endothelial and immune cells will provide novel information to develop therapeutic strategies for sepsis.

Pathogen associated moleculear patterns (PAMPs) and/or damage associated molecular patterns (DAMPs) produced during sepsis, activate endothelial cells to increase the expression of adhesion molecules, attracting immune cell infiltration into the tissues. Uncontrolled inflammatory responses during the early phase …

Convalescent Plasma Therapy In Coronavirus Disease 2019 (Covid-19) Patients: A Brief Review, Muhammad Arif Khan, Ikram Ullah

The University of Louisville Journal of Respiratory Infections

The recent outbreak of the COVID-19 pandemic has caused a re-evaluation of the effectiveness of convalescent plasma therapy (CPT). This review was carried out to assess the usefulness of CPT in critically ill COVID-19 patients based on the published data to date. To the best of our knowledge, this is the second review of the usefulness of CPT in COVID-19 patients. PubMed, Google Scholar, MEDLINE, and Embase databases were searched for relevant reports up to June 21, 2020. Records of published data were analyzed according to eligibility criteria. Five different studies on CPT for critically ill COVID-19 patients were included …

Isotype-Specific Outcomes In Fc Gamma Receptor Targeting Of Pspa Using Fusion Proteins As A Vaccination Strategy Against Streptococcus Pneumoniae Infection, Kari Wiedinger

Seton Hall University Dissertations and Theses (ETDs)

Streptococcus pneumoniae (Spn) remains a considerable threat to public health despite the availability of antibiotics and polysaccharide conjugate vaccines. The lack of mucosal immunity in addition to capsular polysaccharide diversity, has proved to be problematic in developing a universal vaccine against Spn. Targeting antigen to Fc receptors is an attractive way to augment both innate and adaptive immunity against mucosal pathogens, by promoting interactions with activating Fcγ receptors (FcγR) that mediate diverse immunomodulatory functions. The effect of targeting FcγR is highly influenced by the IgG subclass, which bares differential affinities for activating and inhibitory FcγR. In the current study we …

Whims (Washing Hands, Immunity Boost, Masking & Social Distancing), Srinivasan Ragothaman

Creative Work

This is a shot poem about preventing the spread of Covid-19. It pleads general public to wear masks, wash hands, social distance, and boost immunity. It is set to a popular tune in Hindi - Dil Ke Jharoke Mein.