Immunology of Infectious Disease Commons^™

Immunotherapy: Therapy Vs. Enhancement, Mariah Daly

Honors Program Theses

The battle against cancer is a long-standing struggle that has resulted in new information and the development of novel medical technologies. Current research aims to figure out a way to reprogram cells and bodily mechanisms to eliminate those cells that are cancerous without destroying healthy cells in the process. Methods which use the body’s own mechanisms, such as immunotherapy, have shown and continue to show potential for specifically targeting cancer cells. Adoptive T cell therapy is one form of immunotherapy that has gained significant attention and focus in the field. Therapies improve conditions up to the normal state of being, …

The Case For Face Shields: Improving The Covid-19 Public Health Policy Toolkit, Timothy L. Wiemken, Ana Santos Rutschman, Robert Gatter

All Faculty Scholarship

As the United States battles the later stages of the first wave of COVID-19 and faces the prospect of future waves, it is time to consider the practical utility of face shields as an alternative or complement to face masks in the policy guidance. Without face shields specifically noted in national guidance, many areas may be reluctant to allow their use as an alternative to cloth face masks, even with sufficient modification.

In this piece, we discuss the benefits of face shields as a substitute to face masks in the context of public health policy. We further discuss the implications …

Adaptation Of Vibrio Cholerae O1 To Protective, Lipopolysaccharide-Specific Antibodies In The Intestinal Lumen, Danielle Elizabeth Baranova

Legacy Theses & Dissertations (2009 - 2024)

The outer membrane (OM) of Gram-negative enteric pathogens like Vibrio cholerae is a barrier against host defense factors, as well as a sensor of physical and chemical stimuli that the bacteria encounter in the gastrointestinal tract. The OM is also the primary target of the mucosal immune response, which consists of secretory antibodies primarily directed against lipopolysaccharide (LPS). ZAC-3 is a monoclonal antibody (MAb) that targets the conserved core/lipid A region of LPS of the pandemic V. cholerae O1 serotype. In a neonatal mouse model, passively administered ZAC-3 IgG has been shown to reduce the ability of V. cholerae to …

Comments On The Preliminary Framework For Equitable Allocation Of Covid-19 Vaccine, Ana Santos Rutschman, Julia Barnes-Weise, Robert Gatter, Timothy L. Wiemken

All Faculty Scholarship

On September 1, 2020 the National Academies released a draft framework for Equitable Allocation of a COVID-19 Vaccine. In this response, we analyze the proposed framework and highlight several areas.

Among the proposed changes, we highlight the need for the following interventions. The final framework for distribution of COVID-19 vaccines should give a higher priority to populations made most vulnerable by the social determinants of health. It should incorporate more geography-based approaches in at least some of the four proposed phases of vaccine distribution. It should address the possibility of a vaccine being made available through an emergency use authorization …

Assessment Of The Immune Response To Posthodiplostomum Minimum Infection In Bluegills, Olamide S. Olayinka

Masters Theses

Bluegills (Lepomis macrochirus) are common intermediate hosts for white grub (Posthodiplostomum minimum). They tolerate heavy infections with minimal effect on condition and continue to accumulate metacercariae as they age. This suggests that any immune response to this parasite might not be effective. This study was conducted to better understand the immune mechanisms underlying P. minimum infection in bluegills.

Infected organs (liver, kidney, and heart) were examined histologically, and serum from infected fish was tested for antibodies to white grub. Juvenile flukes were recovered from isolated metacercarial cysts. Polyclonal antibodies were produced in mice against white grub …

Role Of Astrocyte-Derived Extracellular Vesicles In Neuroinflammation Mediated By Drug Abuse, Ke Liao

Theses & Dissertations

Neuronal damage and neuroinflammation is a hallmark feature of HIV-associated neurological disorders (HANDs). Opioids abuse accelerates the incidence and progression of HAND; however, the mechanisms underlying the potentiation of neuropathogenesis by these drugs remain elusive. Extracellular vesicles (EVs) are essential conduits in HIV and drug abuse-mediated synaptodendritic injury and neuroinflammation. Findings from our group have demonstrated that astrocyte-derived EV (ADEV)-miRNA-29b mediates HIV Tat and morphine-induced neuronal injury, thus underscoring the importance of such interactions in NeuroHIV.

Besides, HIV Tat and morphine-mediated synaptodendritic injury via ADEVs, we are also interested in whether ADEVs contributes to neuroinflammation. Microglia are critical players in …

The Histoplasma Capsulatum Ddr48 Gene Is Required For Survival Within Macrophages And Resistance To Oxidative Stress And Antifungal Drugs, Logan Blancett

Dissertations

Histoplasma capsulatum(Hc)is a systemic, dimorphic fungal pathogen that affects upwards of 500,000 individuals in the United States annually. Hc grows as a multicellular mold at environmental temperatures; whereas, upon inhalation into a human or other mammalian host, it transforms into a unicellular, pathogenic yeast. The research presented in this dissertation is focused on characterizing the DNA damage-responsive gene HcDDR48. HcDDR48was originally isolated via a subtractive DNA library enriched for transcripts enriched in the mold-phase of Hcgrowth. Upon further analysis we found that HcDDR48is not just expressed in the mold morphotype, but both growth programs …

Mechanism Of Neutrophil Homeostasis And Immunity In Pneumonia And Sepsis, Sagar Paudel

LSU Doctoral Dissertations

Severe bacterial pneumonia and septicemia are pressing health problems. A better understanding of cellular and molecular players of neutrophil immunity and homeostasis in bacterial pneumonia and sepsis is critical for inspiring novel therapeutics. Chemokine CXCL1 is a widely secreted neutrophil attractant and Nod-like receptor (NLRC4) is commonly expressed cytoplasmic pathogen sensor in hematopoietic compartments. How these innate mediators convert pathogen signals into molecular cues of immune response in context of Gram-positive bacterial pneumonia and septicemia largely remain unknown. Utilizing Cxcl1 gene deficient mice, we demonstrate CXCL1 regulates neutrophil influx, bacterial clearance, and host survival in pneumococcal pneumonia-derived sepsis. Furthermore, Cxcl1 …

Nlrp6 In Gram-Positive Pneumonia And Sepsis, Laxman Ghimire

LSU Doctoral Dissertations

Acute lower respiratory infections (pneumonia) and pneumonia-derived sepsis are among the leading causes of death in the world causing 7.8 million deaths annually. In this regard, Methicillin-resistant Staphylococcus aureus (MRSA) is endemic in the US and implicated for causing high mortality-associated necrotizing pneumonia and aggravating viral pneumonia with superinfection. Additionally, sepsis is the 7^th leading cause of death among newborns in the US and is responsible for more than 750,000 hospitalization cases every year. Although there is a plethora of research in both pneumonia and sepsis, the detailed pathophysiology still remains elusive. Understanding the host defense mechanism will help …

A Role Of Ubiquitin Regulatory X-Domain Containing Proteins (Ubxn6) In Antiviral Immunity, Harshada Ketkar, Harshada Ketkar

NYMC Student Theses and Dissertations

The roles of UBXNs in the regulation of antiviral immune responses have not been much explored. Previous work in our lab identified UBXN1 as a negative regulator of the retinoic acid-inducible gene-I (RIG-I) like receptors (RLR) pathway and UBXN3B as a positive regulator of stimulator-of-interferon Genes (STING) -mediated immune responses. In this study, I aimed to determine the member of UBXNs as a positive regulator of ribonucleic acid (RNA) virus infection-induced innate immune responses. By using an interferon stimulated response element (ISRE)-driven luciferase reporter assay that monitors the activity of type I/III interferon (IFN)-induced janus kinase (JAK) - signal transducer …

Environmental Sampling Techniques For Herd-Level Surveillance Of Bovine Viral Diarrhea Virus, Jaden Carlson

School of Veterinary and Biomedical Sciences: Dissertations, Theses, and Student Research

Control of Bovine Viral Diarrhea Virus (BVDV) relies on resource-intensive individual animal sampling to detect and remove persistently infected (PI) cattle. Herd-level surveillance tools would be useful for herds with unknown BVDV status and for monitoring herds with BVDV-free status. The overall objective of this thesis is to explore the viability of BVDV surveillance at a herd-level using samples collected without handling individual animals. The first objective was to determine the feasibility of using stable flies as a sampling tool to detect BVDV. The second objective was to determine the feasibility of using drinking water to detect BVDV. To accomplish …

Elucidating Immune Signaling Of Influenza A Virus And Aspergillus Fumigatus Co-Infections Through Pioneered Model Development, Meagan Danyelle Rippee-Brooks

Graduate Theses/Dissertations

Bacterial co-infections with influenza A virus (IAV) are extremely serious and life-threatening. However, there exists limited understanding about the importance of fungal infections with IAV. Clinical case reports indicate that fungal co-infections do occur and suggest the IAV pandemic of 2009 had a propensity to predispose patients to secondary fungal infections more than previous IAV strains. IAV-fungal co-infections are marked by high mortality rates of 47 to 61% in previously healthy individuals between the ages of 20 and 60. Yet, the variables involved in this co-infection remain undetermined. I achieved effective recapitulation of this co-infection using a C57Bl/6 murine (mouse) …

Development Of Novel Zika And Anthrax Viral Nanoparticle Vaccines, Elizabeth Henderson

KGI Theses and Dissertations

Vaccines protect against numerous infectious diseases and prevent millions of deaths annually, but there are still many infectious diseases for which no licensed vaccine exists. Developing a new vaccine requires balancing safety and efficacy, and viral nanoparticle (VNP) vaccines possess both of these characteristics. The work herein demonstrates how tobacco mosaic virus (TMV) nanoparticles can serve as a platform to create candidate vaccines for Zika virus (ZIKV) and anthrax. In the first study, a ZIKV-specific epitope was genetically fused to TMV to create a safe and inexpensive vaccine that proved highly immunogenic in mice and led to the discovery of …

Combating Tuberculosis: Using Time-Dependent Sensitivity Analysis To Develop Strategies For Treatment And Prevention, Kendall B. Clark, Mayleen Cortez, Cristian Hernandez, Beth E. Thomas, Allison L. Lewis

Spora: A Journal of Biomathematics

Although many organizations throughout the world have worked tirelessly to control tuberculosis (TB) epidemics, no country has yet been able to eradicate the disease completely. We present two compartmental models representing the spread of a TB epidemic through a population. The first is a general TB model; the second is an adaptation for regions in which HIV is prevalent, accounting for the effects of TB/HIV co-infection. Using active subspaces, we conduct time-dependent sensitivity analysis on both models to explore the significance of certain parameters with respect to the spread of TB. We use the results of this sensitivity analysis to …

Role Of Host Cell Β-Catenin During Toxoplasma Gondii Infection, Cameron H. Ranken

Biology ETDs

The microbial pathogen Toxoplasma gondii is an intracellular protozoan that actively invades host cells and simultaneously creates a specialized parasitophorous vacuole within which the parasite lives and replicates. The parasite molecular machinery that drives establishment of the intracellular niche is relatively well known. However, it is now emerging that Toxoplasma exploits less well-understood host cell components to enable successful infection. Here, we examined the role of host Wnt/β-catenin during T. gondii infection. Using human fibroblasts and a mouse dendritic cell line, we found that infection with Toxoplasma stimulated both upregulation and nuclear localization of β-catenin. Using a transwell experimental approach, …

The Wet Bridge Transfer System: An Novel In Vitro Tool For Assessing Exogenous Surfactant As A Pulmonary Drug Delivery Vehicle, Brandon J. Baer

Western Research Forum

Background:

Due to its complex branching structure, direct drug delivery to the remote areas of the lung is a major challenge. Consequently, most therapies, such as those treating pulmonary infection and inflammation, must utilize large systemic dosing, with the potential for adverse side effects. A novel alternative strategy is to use exogenous surfactant, a material capable of distributing throughout the lung, as a pulmonary drug delivery vehicle.

Objective:

Utilize an in vitro transferring system to assess exogenous surfactant (BLES) as a pulmonary delivery vehicle for different therapeutics.

Methods:

An in vitro technique was developed to simultaneously study surfactant delivery and …

Stalking Flu: Development And Characterization Of A Broadly Neutralizing Monoclonal Antibody Targeting The Influenza Hemagglutinin Stem, Elizabeth Newman

NYMC Student Theses and Dissertations

Seasonal epidemics caused by influenza A viruses (IAV) result in an estimated 290,000- 650,000 deaths worldwide each year (17). While antivirals targeted to influenza exist, resistance to these drugs is increasing and regular vaccination remains the most effective way to prevent infection (26, 73, 99). However due to the persistence of antigenic drift and shift, influenza vaccines must be updated each season and antigenic mismatches can reduce efficacy (24, 118). Immunity to influenza either from vaccination or infection is principally mediated by antibodies generated to one of its major surface proteins, Hemagglutinin (HA). HA is a homotrimer, each monomer HA0 …

A Case-Study Approach To Investigate Transmission, Co-Infection, And Clinical Sequelae During Epidemics Of Dengue And Ebola Virus Disease, Jennifer Elizabeth Giovanni

LSU Doctoral Dissertations

From within their ecologic niches, zoonotic viruses emerge from animal reservoirs into the edges and centers of human habitation to exploit opportunities for unabated transmission within immunologically–naïve populations. Our understanding of where, in whom, and how these viruses emerge is under direct challenge, driving the evolution of modern infectious disease epidemiology within a rapidly-connected global community. The studies presented herein are based on analyses of both aggregate and case-level data, which, we argue, provide unique insight into the complexities of transmission, co-infection, and clinical sequelae occurring within, and arising from, epidemics of emerging zoonotic viruses. In Chapter II, we investigate …

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 …

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 …

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 …

Role Of T-Bet In Production Of Immunoglobulin Isotypes In An Influenza Setting, David Sidhom

Honors Undergraduate Theses

Influenza is one of the most common diseases worldwide, yet the vaccines against influenza are only 35% effective at protecting against infection. Creating a more effective vaccine requires an understanding of the foundation and the factors that contribute to a strong and protective adaptive immune response. T-bet [TBX21] is a transcription factor that plays an instrumental role in the orchestration of the type 1 immune response, which is the specialized response used by the immune system for a cell-mediated response against intracellular pathogens, such as influenza. It has yet to be explored in an influenza setting on the role T-bet …

Modulating The Tumor Microenvironment To Induce Cross-Priming For Cancer Immunotherapy, Erica Fleming-Trujillo

Dissertations

Adoptive cell transfer (ACT) using T cells engineered to express tumor-specific T cell receptors (TCR) holds great promise in treating cancer patients. ACT involves the in vitro generation of large numbers of tumor-specific T cells, which are then administered back to the patient, to establish an in vivo response and effective tumor control. Our lab conducted a phase I clinical trial in which metastatic melanoma patients received systemic infusions of autologous T cells transduced to express a tyrosinase-specific TCR (TIL 1383I). We observed tumor regression in one of seven patients and the development of vitiligo, indicative of T cell-mediated killing …

Characterization Of Ovine Monocytes In Response To Haemonchus Contortus Larvae In Vitro And A Novel Role Of Interleukin-13 Inducing Larval Paralysis, Elizabeth Shepherd

Graduate Theses, Dissertations, and Problem Reports (ETD)

Haemonchus contortus is a hematophagous, gastrointestinal parasite affecting small ruminants. Parasitism by H. contortus is the greatest concern of sheep producers in the United States and accounts for billions of dollars in economic loss worldwide. However, different breeds of sheep display differences n natural resistance to H. contortus. St. Croix hair sheep have a remarkable ability to clear H. contortus without the aid of anthelmintics and develop a robust T helper type 2 (Th2) immune response, preventing establishment of infective stage 3 larvae (L3), when compared to susceptible Suffolk sheep. However, the mechanism of development of immune response and …

Binge Alcohol Drinking Exacerbates Ulcerative Colitis Flare, Abigail Cannon

Dissertations

Inflammatory Bowel Disease (IBD) remains a prominent medical concern affecting over 1.4 million people in the U.S. One of the most common forms of the disease is ulcerative colitis (UC), and UC patients will often head doctor's advice to refrain from drinking alcohol. However, whether this phenomenon of alcohol exacerbating UC symptoms occurs is still unknown, which necessitated the generation of a mouse model of UC and binge alcohol. Therefore, we examined a range of DSS concentrations (2-4%) and 2 alcohol paradigms in C57BL/6 mice. Mice receiving 2% DSS ad libitum for five days with a three-day alcohol binge had …

Structure-Guided T Cell Receptor Mutations That Alter Antigen Specificity, Cross-Reactivity, And Polyfunctional Phenotypes In Gene-Modified T Cells, Kendra Foley

Dissertations

Adoptive cell transfer of T cell receptor (TCR) gene-modified T cells targeting specific tumor antigens is currently in clinical trials for patients with advanced malignancies. Despite the clinical responses, there are still hurdles to be overcome in achieving an effective and safe therapy. One of the limitations in the success of this type of therapy is the potential for cross-reactivity and unanticipated off-target reactivity which could lead to autoimmunity. Adverse events encompassing these "off-target, off-tumor" cross-reactivities leading to autoimmunity have been seen in patients in different clinical trials. Here, we demonstrate a novel approach to improve antigen specific reactivity and …

Determination Of Transforming Growth Factor-Β Signaling Targets In Activated T Cells, Ramiah Jacks

Dissertations

T lymphocytes are a critical component of the adaptive immune system and their responses in pathogenic and steady state conditions require strict regulation. One mechanism involved in this regulation is Transforming Growth Factor-β (TGF-β) signaling. TGF-β can act on activated T cells to facilitate the differentiation of TGF-β dependent T helper subsets or the suppression of T cell activation and proliferation. However, the molecular mechanism(s) by which TGF-β signaling controls T cell differentiation vs T cell suppression remain poorly understood.TGF-β signaling is propagated by initially binding to the TGF-β type II receptor, which subsequently activates TGF-β type I receptor (TGF-βRI) …

Protection From Staphylococcus Aureus Bloodstream Infection By Probiotic Exopolysaccharide, Wonbeom Paik

Dissertations

Staphylococcus aureus is known to cause severe systemic infection with high mortality rates. Antibiotics are the only approved therapy for patients, but the widespread prevalence of antibiotic resistant strains limits treatment efficacy, and many patients succumb to the disease. Many probiotic agents are commercially available, but the mechanisms by which they benefit are not known. Understanding these mechanisms will help develop novel therapeutics that can improve healthcare, including systemic infections by S. aureus. Bacillus subtilis is a probiotic bacterium that produces an exopolysaccharide (EPS) that induces anti inflammatory macrophages (MΦ). We tested if EPS could be used for systemic S. …

White-Nose Syndrome And Immune Responses In A Resistant Bat Species (Eptesicus Fuscus), Keslie Skye Naffa

Graduate Theses/Dissertations

White-nose syndrome (WNS) has had a large negative impact on bat populations across eastern North America since its arrival in 2006. Bats affected by WNS appear to die of starvation, possibly due to the increased arousals during hibernation when there is no food present to replace the energy used to arouse. During hibernation, the bat’s immune system should be suppressed. However, once a bat of a susceptible species is exposed to the fungus that causes WNS, Psuedogymnoascus destructans (Pd), the immune system seems to respond, potentially causing an elevation in metabolic rate, which may cause the bat to …

Distribution Of Dengue And Zika Virus Igg Immunoglobulin, Madison Smith, Awadalkareem Adam, Anuja Mathew

Senior Honors Projects

Introduction. Dengue Virus (DENV) and Zika Virus (ZIKV) are viruses that belong to the Flavivirus family. They are transmitted by the Aedes aegypti species of mosquitoes. Infection with DENV can result in no symptoms, mild symptoms which include fever, rash, and headache (dengue fever) or more severe symptoms which include hemorrhage, dengue hemorrhagic fever (DHF) and shock, dengue shock syndrome (DSS). ZIKV, until recently caused mild disease but an outbreak in Brazil was associated with fetal complications such as microcephaly or Guillain-Barré syndrome in adults. Due to the similarity between ZIKV and DENV, antibodies (Abs) generated in humans to these …