Immunology and Infectious Disease Commons^™

A Functional Study Of Topological Dna Problem In Human T Cells During Chronic Viral Infection, Xindi Dang

Electronic Theses and Dissertations

T cells play an important role in adaptive immune system against viral infections, while premature aging and dysfunction of T cells induced by unrepaired DNA damages are always non-negligible snags during the long-term of fighting with chronic viral infections, such as Hepatitis B virus (HBV), Hepatitis C virus (HCV) or Human Immunodeficiency Virus (HIV) infection. In this dissertation, we investigated the role of topological DNA damage in reprogramming telomeric DNA damage responses (DDR), mitochondrial metabolisms, and T cell functions using CD4+ T cells derived from individuals with chronic viral infections or healthy subjects treated with topoisomerase inhibitors. The healthy human …

Danio Rerio: A Past, Present, And Future Hallmark For Immunological Studies, Michael Solomon Chembars Jr.

Senior Honors Theses

An emerging species that is slowly gaining reputation as a common model organism is Danio rerio. Due to its similarities to our own immune response and its general ease of use, hundreds of studies have been conducted which have increased our understanding of how chemicals or pathogens can affect both our own health, and the health of the environment.

This study aims to briefly describe a brief history of D. rerio, as well as discuss key experiments that have been performed using D. rerio. A comparison will also be made between the human and zebrafish immune responses, and …

A Field Synopsis, Systematic Review, And Meta-Analyses Of Cophylogenetic Studies: What Is Affecting Congruence Between Phylogenies?, Valeria Trivellone, Bernd Panassiti

MANTER: Journal of Parasite Biodiversity

We conducted a field synopsis and systematic meta-analysis of studies that carried out cophylogenetic analyses using algorithms and available software. We evaluated the influence of three factors—namely, cophylogenetic method, association, and ecosystem type—on the outcome of the analyses, that is, the degree of congruence between phylogenies of interacting species.

The published papers were identified using 4 different databases and 13 keywords; we included all studies for which statistical approaches to compare phylogenies (cophylogenetic analyses) of interacting lineages were used. After the initial screening, 296 studies were selected to extract response variable (outcome of the cophylogenetic analyses, i.e., congruent, incongruent, or …

The First Complete Genome Of The Simian Malaria Parasite Plasmodium Brasilianum, Marko Bajic, Shashidhar Ravishankar, Mili Sheth, Lori A. Rowe, M. Andreina Pacheco, Dhruviben S. Patel, Dhwani Batra, Vladimir Loparev, Christian Olsen, Ananias A. Escalante, Fredrik Vannberg, Venkatachalam Udhayakumar, John W. Barnwell, Eldin Talundzic

Harold W. Manter Laboratory of Parasitology: Library Materials

Naturally occurring human infections by zoonotic Plasmodium species have been documented for P. knowlesi, P. cynomolgi, P. simium, P. simiovale, P. inui, P. inui-like, P. coatneyi, and P. brasilianum. Accurate detection of each species is complicated by their morphological similarities with other Plasmodium species. PCR-based assays offer a solution but require prior knowledge of adequate genomic targets that can distinguish the species. While whole genomes have been published for P. knowlesi, P. cynomolgi, P. simium, and P. inui, no complete genome for P. brasilianum has …

Polyphenolics, Glucosinolates And Isothiocyanates Profiling Of Aerial Parts Of Nasturtium Officinale (Watercress), Sotiris Kyriakou, Kyriaki Michailidou, Tom Amery, Kyle Stewart, Paul G. Winyard, Dimitrios T. Trafalis, Rodrigo Franco, Aglaia Pappa, Mihalis I. Panayiotidis

School of Veterinary and Biomedical Sciences: Faculty Publications

Watercress (Nasturtium officinale) is a rich source of secondary metabolites with disease-preventing and/or health-promoting properties. Herein, we have utilized extraction procedures to isolate fractions of polyphenols, glucosinolates and isothiocyanates to determine their identification, and quantification. In doing so, we have utilized reproducible analytical methodologies based on liquid chromatography with tandem mass spectrometry by either positive or negative ion mode. Due to the instability and volatility of isothiocyanates, we followed an ammonia derivatization protocol which converts them into respective ionizable thiourea derivatives. The analytes’ content distribution map was created on watercress flowers, leaves and stems. We have demonstrated that …

Tumor-Intrinsic Sirpa Promotes Sensitivity To Checkpoint Inhibition Immunotherapy In Melanoma, Zhicheng Zhou, Mei-Ju May Chen, Yikai Luo, Kamalika Mojumdar, Xin Peng, Hu Chen, Shweta V Kumar, Rehan Akbani, Yiling Lu, Han Liang

Faculty, Staff and Student Publications

Checkpoint inhibition immunotherapy has revolutionized cancer treatment, but many patients show resistance. Here we perform integrative transcriptomic and proteomic analyses on emerging immuno-oncology targets across multiple clinical cohorts of melanoma under anti-PD-1 treatment, on both bulk and single-cell levels. We reveal a surprising role of tumor-intrinsic SIRPA in enhancing antitumor immunity, in contrast to its well-established role as a major inhibitory immune modulator in macrophages. The loss of SIRPA expression is a marker of melanoma dedifferentiation, a key phenotype linked to immunotherapy efficacy. Inhibition of SIRPA in melanoma cells abrogates tumor killing by activated CD8+ T cells in a co-culture …

Modeling The Impact Of Hospitalization On The Death Rate Of An Ebola Outbreak, Erin N. Bodine, Jana V. Turner

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Unraveling The Complex Interactions Between Members Of The Schistosoma Haematobium Group And Bulinus Snails In And Around Lake Victoria In West Kenya, Caitlin Raiselle Babbitt

Biology ETDs

Schistosoma haematobium, the agent of urogenital schistosomiasis, and related schistosomes are transmitted by members of the genus Bulinus. Each of the 38 Bulinus species vary in their ability to vector schistosome species and non-schistosome trematodes resulting in a patchwork of snail-parasite compatibilities. Accurately identifying snail intermediate hosts and the disease-causing parasites they transmit is critical for snail control strategies and the management of human schistosomiasis. Towards these ends, this thesis identifies bulinid species and the parasites they transmit and implicates certain species in the transmission of S. haematobium. The thesis also includes a systematic review of methods …

Cardiac Myosin-Specific Autoimmune T Cells Contribute To Immune-Checkpoint-Inhibitor-Associated Myocarditis, Johns Hopkins University School Of Medicine, Johns Hopkins University Bloomberg School Of Public Health, Johns Hopkins University Whiting School Of Engineering, Ninaad Lasrado, Jay Reddy, Daniela Ciháková

School of Veterinary and Biomedical Sciences: Faculty Publications

Immune checkpoint inhibitors (ICIs) are an effective therapy for various cancers; however, they can induce immune-related adverse events (irAEs) as a side effect. Myocarditis is an uncommon, but fatal, irAE caused after ICI treatments. Currently, the mechanism of ICI-associated myocarditis is unclear. Here, we show the development of myocarditis in A/J mice induced by anti-PD-1 monoclonal antibody (mAb) administration alone without tumor cell inoculation, immunization, or viral infection. Mice with myocarditis have increased cardiac infiltration, elevated cardiac troponin levels, and arrhythmia. Anti-PD-1 mAb treatment also causes irAEs in other organs. Autoimmune T cells recognizing cardiac myosin are activated and increased …

The Stockholm Paradigm: Lessons For The Emerging Infectious Disease Crisis, Daniel R. Brooks, Walter A. Boeger, Eric P. Hoberg

MANTER: Journal of Parasite Biodiversity

The emerging infectious disease (EID) crisis represents an immediate existential threat to modern humanity. Current policies aimed at coping with the EID crisis are ineffective and unsustainably expensive. They have failed because they are based on a scientific paradigm that produced the parasite paradox. The Stockholm paradigm (SP) resolves the paradox by integrating four elements of evolutionary biology: ecological fitting, sloppy fitness space, coevolution, and responses to environmental perturbations. It explains why and how the EID crisis occurs and is expanding and what happens after an EID emerges that sets the stage for future EIDs. The SP provides a number …

The Dama Protocol, An Introduction: Finding Pathogens Before They Find Us, Eric P. Hoberg, Walter A. Boeger, Orsolya Molnár, Gábor Földvári, Scott L. Gardner, Alicia Juarrero, Vitaliy A. Kharchenko, Eloy Ortiz, Wolfgang Preiser, Valeria Trivellone, Daniel R. Brooks

MANTER: Journal of Parasite Biodiversity

Globally, humanity is coming to recognize the magnitude of the interactive crisis for emerging infectious disease (EID). Strategies for coping with EID have been largely in the form of reactive measures for crisis response. The DAMA protocol (Document, Assess, Monitor, Act), the operational policy extension of the Stockholm paradigm, constitutes a preventive/proactive dimension to those efforts. DAMA is aimed at focusing and extending human and material resources devoted to coping with the accelerating wave of EID. DAMA is integrative, combining efforts to strategically document the distribution of complex pathogen and host assemblages in the biosphere in the context of dynamic …

Role Of Cd38 In Pulmonary Host Defense Against Gram-Negative Pneumonia, Xiaoqian Shan

LSU Master's Theses

The Gram-negative bacterium, Klebsiella pneumoniae, is a major cause of hospital-acquired pneumonia in the U.S. In particular, the dramatic increase in carbapenem-resistant K. pneumoniae infections poses a serious threat to the public health both in the United States and worldwide. Clearance of bacteria in the lungs depends on effective pulmonary immune response. It may be possible to design improved therapies that augment host immune responses while attenuating excessive pulmonary inflammation through modulation of key innate immunity molecules during pneumonic infections. Cluster differentiation CD38 (CD38) has been detected on the surface of many immune cells or intracellular compartments, acting as …

Louis Pasteur Signature Saying: Science Brings Men Closer To God Bicentenary Year: 200 Years After His Birth, Alan L. Gillen, Justin A. Ambrose

Faculty Publications and Presentations

This year (2022) marks the bicentenary birth (December 27, 1822) of Louis Pasteur. He has a global reputation. His contributions can be seen in our homes, in the "pasteurized" products derived from one of his discoveries and in disease prevention. It was in his discovery of gently heating beverages and food for what we today call pasteurization that he first said: “Man's first look at the universe discovers only variety, diversity, multiplicity of phenomena. Let this gaze be enlightened by science — by science which brings man closer to God — and simplicity and unity shine everywhere.” Louis Pasteur (Vallery-Radot, …

Immune Dysfunction Signatures Predict Outcomes And Define Checkpoint Blockade-Unresponsive Microenvironments In Acute Myeloid Leukemia, Sergio Rutella, Jayakumar Vadakekolathu, Francesco Mazziotta, Stephen Reeder, Tung-On Yau, Rupkatha Mukhopadhyay, Benjamin Dickins, Heidi Altmann, Michael Kramer, Hanna A Knaus, Bruce R Blazar, Vedran Radojcic, Joshua F Zeidner, Andrea Arruda, Bofei Wang, Hussein A Abbas, Mark D Minden, Sarah K Tasian, Martin Bornhäuser, Ivana Gojo, Leo Luznik

Faculty, Staff and Student Publications

Background

Immune exhaustion and senescence are dominant dysfunctional states of effector T cells and major hurdles for the success of cancer immunotherapy. In the current study, we characterized how acute myeloid leukemia (AML) promotes the generation of senescent-like CD8⁺ T cells and whether they have prognostic relevance.

METHODS

We analyzed NanoString, bulk RNA-Seq and single-cell RNA-Seq data from independent clinical cohorts comprising 1,896 patients treated with chemotherapy and/or immune checkpoint blockade (ICB).

Results

We show that senescent-like bone marrow CD8⁺ T cells were impaired in killing autologous AML blasts and that their proportion negatively correlated with overall survival …

T Cells Specific For Α-Myosin Drive Immunotherapy-Related Myocarditis, Margaret L Axelrod, Wouter C Meijers, Elles M Screever, Juan Qin, Mary Grace Carroll, Xiaopeng Sun, Elie Tannous, Yueli Zhang, Ayaka Sugiura, Brandie C Taylor, Ann Hanna, Shaoyi Zhang, Kaushik Amancherla, Warren Tai, Jordan J Wright, Spencer C Wei, Susan R Opalenik, Abigail L Toren, Jeffrey C Rathmell, P Brent Ferrell, Elizabeth J Phillips, Simon Mallal, Douglas B Johnson, James P Allison, Javid J Moslehi, Justin M Balko

Faculty, Staff and Student Publications

Immune-related adverse events, particularly severe toxicities such as myocarditis, are major challenges to the utility of immune checkpoint inhibitors (ICIs) in anticancer therapy1. The pathogenesis of ICI-associated myocarditis (ICI-MC) is poorly understood. Pdcd1-/-Ctla4+/- mice recapitulate clinicopathological features of ICI-MC, including myocardial T cell infiltration2. Here, using single-cell RNA and T cell receptor (TCR) sequencing of cardiac immune infiltrates from Pdcd1-/-Ctla4+/- mice, we identify clonal effector CD8+ T cells as the dominant cell population. Treatment with anti-CD8-depleting, but not anti-CD4-depleting, antibodies improved the survival of Pdcd1-/-Ctla4+/- mice. Adoptive transfer of immune cells from mice with myocarditis induced fatal myocarditis in recipients, …

The Effects Of Covid-19 On Residential Municipal Waste Streams, Anne Kluthe

Honors Program: Senior Projects (Public)

Through interviews, this exploratory analytive study researched how COVID-19, and especially the first lockdown of 2020, changed residential municipal waste streams, specifically in terms of items, tonnage, and workplace practices. The most common items were an influx in PPE, specifically face masks, and an increase in cardboard. There was also some evidence of paper from “deep cleaning” projects and construction debris from backyard pool installation and bathroom renovation. The total change in waste varied from area to area. Norfolk and the surrounding area had a stagnant amount of waste during the pandemic, Omaha and the rest of Douglas County saw …

The 3p Framework: A Comprehensive Approach To Coping With The Emerging Infectious Disease Crisis, Orsolya Molnár, Eric Hoberg, Valeria Trivellone, Gábor Földvári, Daniel R. Brooks

MANTER: Journal of Parasite Biodiversity

The COVID-19 pandemic is the latest example of the profound socioeconomic impact of the emerging infectious disease (EID) crisis. Current health security measures are based on a failed evolutionary paradigm that presumes EID is rare and cannot be predicted because emergence requires the prior evolution of novel genetic capacities for colonizing a new host. Consequently, crisis response through preparation for previously emerged diseases and palliation following outbreaks have been the only health security options, which have become unsustainably expensive and unsuccessful. The Stockholm paradigm (SP) is an alternative evolutionary framework that suggests host changes are the result of changing conditions …

Cftr Deletion In Mouse Epithelial And Immune Cells Differentially Influence The Intestinal Microbiota, Callie E. Scull, Meng Luo, Scott Jennings, Christopher M. Taylor, Guoshun Wang

School of Medicine Faculty Publications

Cystic fibrosis (CF) is a life-threatening genetic disorder, caused by mutations in the CF transmembrane-conductance regulator gene (cftr) that encodes CFTR, a cAMP-activated chloride and bicarbonate channel. Clinically, CF lung disease dominates the adult patient population. However, its gastrointestinal illness claims the early morbidity and mortality, manifesting as intestinal dysbiosis, inflammation and obstruction. As CF is widely accepted as a disease of epithelial dysfunction, it is unknown whether CFTR loss-of-function in immune cells contributes to these clinical outcomes. Using cftr genetic knockout and bone marrow transplantation mouse models, we performed 16S rRNA gene sequencing of the intestinal microbes. Here we …

Using The Embl-Ebi Clustal Omega Tool To Calculate Diversity Of Heavy Chain Phage-Display Libraries, Michael Bodri, Shane A. Webb

Georgia Journal of Science

Here we show that traditional Sanger sequencing combined with analysis tools available from the European Molecular Biology Laboratory-European Bioinformatics Institute (EMBL-EBI), specifically EMBOSS Transeq and Clustal Omega, is extremely effective in the analysis of naïve phage display antibody libraries for the determination of library size and diversity. The free tools are easy to use and require little manipulation of reads by hand, allowing analysis to be performed on a standard personal computer. Utilization of this technique has applicability to researchers with limited access to deep sequencing. The primary drawback to this analysis methodology is that antibodies with particular molecular or …

Whole Genome Sequencing Of Moraxella Bovis Strains From North America Reveals Two Genotypes With Different Genetic Determinants, Emily L. Wynn, Matthew M. Hille, John Dustin Loy, Gennie Schuller, Kristen L. Kuhn, Aaron M. Dickey, James L. Bono, Michael L. Clawson

School of Veterinary and Biomedical Sciences: Faculty Publications

Background: Moraxella bovis and Moraxella bovoculi both associate with infectious bovine keratoconjunctivitis (IBK), an economically significant and painful ocular disease that affects cattle worldwide. There are two genotypes of M. bovoculi (genotypes 1 and 2) that differ in their gene content and potential virulence factors, although neither have been experimentally shown to cause IBK. M. bovis is a causative IBK agent, however, not all strains carry a complete assortment of known virulence factors. The goals of this study were to determine the population structure and depth of M. bovis genomic diversity, and to compare core and accessory genes and …

Poliovirus Immunity Among Children Aged 6-11 And 36-48 Months In 14 Polio High-Risk Provinces Of Afghanistan: A Health-Facility-Based Study, Sajid Bashir Soofi, Maureen Martinez, Noha H. Farag, William S. Hendley, Derek Ehrhardt, Imran Ahmed, Imtiaz Hussain, William Weldon, Ahmed M. Kassem

Department of Paediatrics and Child Health

Afghanistan is one of two countries where wild poliovirus (WPV) type 1 remains endemic. We conducted a facility-based cross-sectional survey of antipoliovirus antibodies in children in 14 provinces of Afghanistan. The provinces were selected based on programmatic priorities for polio eradication. Children aged 6-11 and 36-48 months attending outpatient clinics were enrolled in the study. We collected venous blood, isolated serum, and conducted neutralization assays to detect poliovirus neutralizing antibodies. A total of 2086 children from the 14 provinces were enrolled. Among the enrolled children, 44.3% were girls; the median age in the 6-11-month group was 9.4 months, and in …

Machine Learning On Syngeneic Mouse Tumor Profiles To Model Clinical Immunotherapy Response, Zexian Zeng, Shengqing Stan Gu, Cheryl J Wong, Lin Yang, Nofal Ouardaoui, Dian Li, Wubing Zhang, Myles Brown, X Shirley Liu

Faculty, Staff and Student Publications

Most patients with cancer are refractory to immune checkpoint blockade (ICB) therapy, and proper patient stratification remains an open question. Primary patient data suffer from high heterogeneity, low accessibility, and lack of proper controls. In contrast, syngeneic mouse tumor models enable controlled experiments with ICB treatments. Using transcriptomic and experimental variables from >700 ICB-treated/control syngeneic mouse tumors, we developed a machine learning framework to model tumor immunity and identify factors influencing ICB response. Projected on human immunotherapy trial data, we found that the model can predict clinical ICB response. We further applied the model to predicting ICB-responsive/resistant cancer types in …

Activity Of The Lactate Dehydrogenase Inhibitor Oxamic Acid Against The Fermentative Bacterium Streptococcus Mitis/Oralis: Bactericidal Effects And Prevention Of Daptomycin Resistance In Vitro And In An Ex Vivo Model, Razieh Kebriaei, Arnold S. Bayer, Christian K. Lapitan, Michael J. Rybak, Greg A. Somerville, Nagendra N. Mishra

School of Veterinary and Biomedical Sciences: Faculty Publications

Streptococcus mitis/oralis is a fermentative bacterium that relies on lactate dehydrogenase to balance its redox poise and keep glycolysis active. Metabolomic analysis of an in vitro– derived daptomycin-resistant (DAP-R) S. mitis/oralis strain (351-D10) revealed differences in glucose catabolism relative to its DAP-susceptible (DAP-S) parental strain, 351. Metabolic changes associated with the transition to this DAP-R phenotype suggested that inhibiting glycolysis could alter DAP susceptibility. In addition, the strong reliance of S. mitis/oralis on glycolysis for energy and biosynthetic intermediates suggested that inhibiting glycolysis would adversely affect growth and biomass accumulation. To test these hypotheses, we used the lactate dehydrogenase inhibitor …

The Effect Of Infection Risk On Female Blood Transcriptomics, Brenna M. G. Gormally, Patricia C. Lopes

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Defenses against pathogens can take on many forms. For instance, behavioral avoidance of diseased conspecifics is widely documented. Interactions with these infectious conspecifics can also, however, lead to physiological changes in uninfected animals, an effect that is much less well understood. These changes in behavior and physiology are particularly important to study in a reproductive context, where they can impact reproductive decisions and offspring quality. Here, we studied how an acute (3 h) exposure to an immune-challenged male affected female blood transcriptomics and behavior. We predicted that females paired with immune-challenged males would reduce eating and drinking behaviors (as avoidance …

Morphometric And Molecular Characterization Of An Unpigmented Haemosporidian Parasite In The Neotropical Turnip-Tailed Gecko (Thecadactylus Rapicauda), Nubia E. Matta, Leydy P. González, Mario Vargas-Ramírez, Gediminas Valkiūnas, Ananias A. Escalante, M. Andreína Pacheco

Harold W. Manter Laboratory of Parasitology: Library Materials

Morphological traits from blood stages have been the gold standard for determining haemosporidian parasite species. However, the status of some taxa and the value of such traits in parasites from reptiles remain contentious. The scarce sampling of these species worsens the situation, and several taxa lack molecular data. A survey was performed in the Magdalena Department in Colombia, where 16 species of reptiles were captured. A peculiar haemosporidian parasite was found in the Turnip-tailed gecko Thecadactylus rapicauda. This haemosporidian does not show malarial pigment in blood stages under light microscopy; thus, it fits the Garnia genus’s characters belonging to …

Identifying Androgens As A Protective Agent In The Allergic Immune Response To Peanut, Mckenna Vininski

Biology Theses, Dissertations, and Student Creative Activity

Peanut (PN) allergy is a major public health concern. Prevalence of PN allergy has been on the rise for decades due to poor prevention information and a lack of knowledge about the allergic mechanism. Recent research has brought clarity about how individuals become sensitized with routes known through the skin, as well as the airway. Factors influence the allergic immune response, however, based on a known sex difference in allergic asthma and food allergy demographics showing a sex difference, this thesis work hypothesized that a sex difference would exist in PN allergy. This study utilized a 4-week inhalation mouse model …

European House Borer Regulations, Department Of Primary Industries And Regional Development, Western Australia

Biosecurity factsheets

Pinewood movement restrictions

To minimise the spread of EHB in Western Australia (WA), restrictions on the movement of pinewood were implemented in 2006, and currently apply to areas where EHB occurs. By restricting the movement of pinewood from EHB infested areas, EHB has been contained to Restricted Movement Zones (RMZs) in the greater Perth metropolitan area.

The restrictions are described in the Agriculture and Related Resources Protection (European House Borer) Regulations 2006.

The regulations allowed for the establishment of quarantine zones, Priority Management Zones (PMZs) and RMZs, and placed restrictions not only on untreated pinewood movement from PMZs and RMZs …

Glutathione And Glutaredoxin In Redox Regulation And Cell Signaling Of The Lens, Marjorie F. Lou

School of Veterinary and Biomedical Sciences: Faculty Publications

The ocular lens has a very high content of the antioxidant glutathione (GSH) and the enzymes that can recycle its oxidized form, glutathione disulfide (GSSG), for further use. It can be synthesized in the lens and, in part, transported from the neighboring anterior aqueous humor and posterior vitreous body. GSH is known to protect the thiols of the structural lens crystallin proteins from oxidation by reactive oxygen species (ROS) so the lens can maintain its transparency for proper visual function. Age-related lens opacity or senile cataract is the major visual impairment in the general population, and its cause is closely …

A Case Study Investigating Perceptions Of The Covid-19 Vaccine In Cato Manor And Chesterville, Caitlin Chan

Independent Study Project (ISP) Collection

Despite countries all over the world transitioning to life post COVID-19, there are still many aspects of the pandemic that remain controversial and hot topics of debate. Perhaps among one of the most debated subjects is the question of whether vaccinations are necessary and if they truly had an impact on eliminating the virus. The concept of vaccine hesitancy has become a growing concern and threatens the health of communities around the world.

This project employed a mixed-methodology research design to investigate attitudes towards the COVID-19 vaccine constructed by community members living in the townships of Cato Manor and Chesterville. …

Elucidating The Mechanisms Underlying How Vmp1 Regulates Inflammatory Responses, Stephanie Zack

Dissertations

autophagy, inflammation, mitochondria, NLRP3 inflammasome, SERCA, VMP1