Immunology and Infectious Disease Commons^™

Visualization And Characterization Of The Immunological Synapse Between Chlorotoxin Chimeric Antigen (Cltx-Car) Redirected T Cells And Targeted Glioblastoma Tumors, Arianna Livi

CMC Senior Theses

Chimeric Antigen Receptor T (CAR-T) cells have demonstrated anti-tumor activity against aggressive and invasive cancers such as glioblastoma (GBM); however, clinical response rates remain low in clinical trial studies. Tumor heterogeneity and tumor microenvironment conditions pose significant challenges for treatment of GBM, thus continuous optimization of CAR-T cell therapies and identification of novel, widely expressed, and highly specific GBM antigens are vital to better patient outcomes. A newly developed CAR-T cell construct incorporating chlorotoxin (CLTX) as the targeting domain exhibited broad GBM-targeting capabilities and elicited potent cytotoxic effects during preclinical studies and is currently being tested in a phase I …

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.

Multipatch Stochastic Epidemic Model For The Dynamics Of A Tick-Borne Disease, Milliward Maliyoni, Holly D. Gaff, Keshlan S. Govinder, Faraimunashe Chirove

Biological Sciences Faculty Publications

Spatial heterogeneity and migration of hosts and ticks have an impact on the spread, extinction and persistence of tick-borne diseases. In this paper, we investigate the impact of between-patch migration of white-tailed deer and lone star ticks on the dynamics of a tick-borne disease with regard to disease extinction and persistence using a system of Itô stochastic differential equations model. It is shown that the disease-free equilibrium exists and is unique. The general formula for computing the basic reproduction number for all patches is derived. We show that for patches in isolation, the basic reproduction number is equal to the …

Anti-Tick Vaccine Candidate Subolesin Is Important For Blood Feeding And Innate Immune Gene Expression In Soft Ticks, Krittika Nandy, Comfort Tamakloe, Daniel E. Sonenshine, Hameeda Sultana, Girish Neelakanta

Biological Sciences Faculty Publications

Subolesin is a conserved molecule in both hard and soft ticks and is considered as an effective candidate molecule for the development of anti-tick vaccine. Previous studies have reported the role of subolesin in blood feeding, reproduction, development, and gene expression in hard ticks. However, studies addressing the role of subolesin in soft ticks are limited. In this study, we report that subolesin is not only important in soft tick Ornithodoros turicata americanus blood feeding but also in the regulation of innate immune gene expression in these ticks. We identified and characterized several putative innate immune genes including Toll, Lysozyme …

Corrigendum: Characterization Of A Novel Transitional Group Rickettsia Species (Rickettsia Tillamookensis Sp. Nov.) From The Western Black-Legged Tick, Ixodes Pacificus, David T. Gauthier, Sandor E. Karpathy, Stephanie L. Grizzard, Dhwani Batra, Lori A. Rowe, Christopher D. Paddock

Biological Sciences Faculty Publications

No abstract provided.

Investigating The Relationship Between Metabolic Reprogramming And Peripheral Cd4+ T-Cell Inflammation In Human Type 2 Diabetes Pathogenesis, Gabriella Kalantar

Theses and Dissertations--Microbiology, Immunology, and Molecular Genetics

Chronic, low-grade systemic inflammation rises in obesity and promotes type 2 diabetes (T2D). Circulating immune cells are key indicators of obesity and T2D pathogenesis. T cells outnumber monocytes, in blood, suggesting that T cells might fuel peripheral inflammation in obesity/T2D. Our lab’s work supports this idea by identification of a Th17 cytokine profile in T2D from T-cell stimulated peripheral blood mononuclear cells. Work described herein further supported this work by demonstrating that T cells dominate peripheral inflammation over monocytes across the spectrum of obesity and glycemic control. Our lab has also recently shown that inflammation changes during prediabetes (preT2D), identified …

Relative Adrenal Insufficiency In Sepsis, Dan Hao

Theses and Dissertations--Pharmacology and Nutritional Sciences

Sepsis is a leading cause of death in children. Glucocorticoid (GC) therapy had been strongly recommended for the pediatric sepsis (grade 1A). However, the recommendation was changed to grade 2C in 2020 due to weak evidence. Relative adrenal insufficiency (RAI) is a condition characterized by impaired inducible glucocorticoid (iGC) production in response to stress. It develops in 32.8% of pediatric septic patients. Unfortunately, little is known about the pathogenesis of RAI in pediatric sepsis, and whether GC therapy should be based on the status of RAI is controversial. In this study, we utilized 21-day-old SF1CreSRBI^fl/fl mice as the first …

Receptor Usage And Infection Biology Of Influenza D Virus, Tirth Uprety

Theses and Dissertations--Veterinary Science

Influenza D virus (IDV) utilizes bovines as a primary reservoir with periodical spillover to other hosts. We have previously demonstrated by the traditional hemagglutination assay coupled with sialoglycan microarray and functional assays that IDV can recognize and bind both 9-O-acetylated N-acetylneuraminic acid (Neu5,9Ac₂) and 9-O-acetylated N-glycolylneuraminic acid (Neu5Gc9Ac). Agricultural animals such as cattle can produce both Neu5,9Ac₂ and Neu5Gc9Ac, while humans are genetically unable to synthesize Neu5Gc9Ac. The bifunctional enzyme, glucosamine (UDP-N-acetyl)-2-epimerase/N-acetylmannosamine kinase (GNE) is a master regulator of de-novo sialic acid synthesis while 9-O-Acetylation of sialic acids is catalyzed by …

Examining The Immune Regulation Of Nlrp12 Through Novel Protein Interactions, Catherine Rippe

Graduate Theses/Dissertations

NOD-like receptors (NLRs) are intracellular proteins that play an important role in the regulation of the innate immune response to pathogens. Since being identified, various functions for NOD-like receptor pyrin domain containing 12 (NLRP12) have been suggested. It has been shown to negatively regulate the inflammatory response through canonical and noncanonical NF-kB signaling pathways, control tumorigenesis and gut homeostasis and exacerbate inflammation through the formation of a multi-protein complex called an inflammasome. Due to the varying roles established for NLRP12, the mechanisms by which it functions remain poorly understood. In this study, I sought to confirm a novel protein-protein interaction …

Investigating Mirna Regulation Of The Human Apobec3 Enzymes, William Dietrich

All Graduate Theses, Dissertations, and Other Capstone Projects

The human apolipoprotein B mRNA editing enzyme catalytic polypeptide 3 (APOBEC3, A3) are a family of proteins consisting of seven enzymes, A3A, B, C, D, F, G and H, which function as cytosine deaminases. The enzymes’ purpose in the cell is to mutate viral DNA during infection hindering or stopping replication of viruses such as human papillomavirus, herpes simplex virus, and HIV-1. Several of the A3 enzymes have also been implicated in contributing to cancers such as head and neck and breast cancers by mutating cellular genomic DNA, making the ability to control A3 expression an attractive target for cancer …

Odd Bedfellows & Marriage Of Necessity: Public Health And Politics In American Federalism, Gabriella Victoria Chianese

Honors Theses and Capstones

In the wake of the coronavirus disease 2019 (COVID-19) pandemic, while the public disagrees over mask mandates, required vaccinations, and social distancing, it seems like one common sentiment exists – a distaste for the odd bedfellows of politics and public health. There are those who cry for the compartmentalization of the science of public health and the art of politics to rectify this situation. In the wake of so much confusion and chaos, it is not unjustified to demand the depoliticization of public health; however, this response is unrealistic given the modern political climate, demonstrates a narrow understanding of the …

Vitamin D Enhanced Vitamin D Receptor (Vdr) Inhibition Of Nlrp3 Inflammasome Activation Can Attenuate The Development Of Autoimmune Thyroiditis, Alexzon Mandac

Capstone Showcase

Autoimmune Thyroiditis (AIT) is a prevalent autoimmune disease affecting approximately 2% of the population. Characterized by the gradual loss of thyroid function through an autoimmune attack on the thyroid gland, the disease manifests symptoms that negatively affect one’s quality of life. The mechanisms behind the disease’s pathophysiology are not fully understood; however, researchers are examining the involvement of the NLRP3 inflammasome in the disease. This thesis will address the question of whether Vitamin D can act as an inhibitor of the NLRP3 inflammasome and attenuate the progression of AIT in mouse model. Current investigations explore the effects of NLRP3 inhibition …

What Costimulatory Domains In Chimeric Antigen Receptor T Cells Induce The Strongest Killing Response And Increase Serial Killing Efficacy Against Pediatric Rhabdomyosarcomas And Osteosarcomas?, Kristen Wilkins

Longwood Senior Thesis Proposal

No abstract provided.

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’ …

Complex Narratives Of Individuals Living With Alpha-Gal Syndrome (Ags). A Mixed-Methods Investigation: Examined Through Self-Reported Data, In-Person Interviews, And A Group Body Mapping Art Therapy Intervention, Sylvan Streightiff

Art Therapy | Master's Theses

Alpha-gal (galactose-α-1,3-galactose) Syndrome or AGS is an under-recognized chronic condition which coincides with tick-bite exposure, resulting in a unique allergy to non-primate mammalian products and byproducts (in addition to other items caring the α-gal epitope such as carrageenan, agar-agar, and nori). This paper explores the experiences of individuals with this illness, establishing psychological context for expressed symptomatology, while emphasizing the complex trauma rooted in the population’s experiences of the life-altering and life-threatening contexts associated with managing AGS. This research is structured with Acceptance and Commitment Therapy (ACT) theory and utilizes a mixed-methods approach to arts-based research with the goal of …

Intestinal Parasite Infection In Tibetan Macaques (Macac Thebetana) In Eastern China, Miarisoa Ramilison

All Master's Theses

Grooming is one of the crucial social behaviors of primate species that functions to remove parasites and maintain social bonds. Although, much data exists to support the idea that grooming is essential in forming and sustaining social bonds among individuals, there is a lack of information about the extent to which it removes ectoparasites or contributes to the spread of internal parasites. To fill this gap in the literature, we investigated the relationship between social contact behavior including grooming and intestinal parasite infection in Tibetan macaques (Macaca thibetana). This species lives at Mt. Huangshan in China. We used …

Meta-Narrative Review Of Pd-L1 By Immunotherapy On Triple-Negative Breast Cancer, Hannah Lazo, Tyler Harris, Hao Truong, Alina Masroor

Research Methods Poster Session 2023

Triple-negative breast cancer (TNBC) is an aggressive form of subtype breast cancer and there are currently new treatments being discovered such as the combination of immunotherapy and chemotherapy. In immunotherapy against triple-negative breast cancer, checkpoint inhibitors like PD-1/PD-L1 treat TNBC by blocking the “off” signal that prevents T-cells from killing cancer cells. As a group, we conducted a meta-narrative review collecting results from primary sources such as clinical trials and human experimental studies to support our research question on how PD-L1 inhibitor treatments compare to other treatments in patients with TNBC. The review included articles searched from Embase, Pubmed, EMBASE, …

Evaluation Of Leishmanicidal Activities Of 4-Thiazolidinones Against Leishmania Major, The Causative Agent Of Human Cutaneous Leishmaniasis, Kiera Bush

All Master's Theses

The leishmaniases are a group of vector-borne parasitic diseases that affect many developing countries including parts of Africa, India, and the Middle East in addition to Southern Europe and the Americas. It is estimated that worldwide, there are about 3 million new cases of leishmaniases each year leading to as many as 50,000 fatalities annually. The parasites that cause leishmaniasis belong to the genus Leishmania spp and are transmitted by the female phlebotomine sand fly. There are three clinical forms of the infection: visceral, mucocutaneous, and cutaneous. However, the focus of this paper is on cutaneous leishmaniasis that causes skin …

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 …

Localized Delivery Of Gm-Csf In The Regulation Of Breast Tumor Oxygen And Anti-Tumor Immunity Through Macrophages, Nicole E. Mihalik

Graduate Theses, Dissertations, and Problem Reports (ETD)

GM-CSF has been employed as an adjuvant to cancer immunotherapies in solid tumors due to its ability to drive immune stimulatory macrophages and other myeloid cells that promote anti-tumor responses. However, GM-CSF does not always exert immune stimulatory effects on myeloid cells, and sometimes even drives immune suppressive phenotypes. GM-CSF effects on myeloid cells and the tumor microenvironment (TME) appear to vary across dosages and even cancer types. However, an optimal dosing regimen for GM-CSF has yet to be determined to-date, and this is further complicated by the fact that GM-CSF is often administered via oncolytic viruses or tumor vaccines …

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 …

The Development Of A New Pertussis Booster Formulation Via The Implementation Of New Adjuvants And Utilization Of Alternate Routes Of Administration, Megan Ashley Dejong

Graduate Theses, Dissertations, and Problem Reports (ETD)

Pertussis (whooping cough) is a respiratory disease caused by airborne transmission of the Gram-negative bacterium, Bordetella pertussis. Prior to the development of the first pertussis vaccines (whole cell (wP) vaccines), the incidence of pertussis was in the hundreds of thousands of cases per year, which led to the death of many children, as the infection is most severe in younger populations. Thankfully, the wP formulation resulted in a dramatic decrease in the number of annual pertussis cases, nearly eradicating the disease. However, as wP contained the whole B. pertussis bacterium (and its lipooligosaccharide (LOS)), reactogenicity issues became apparent, leading …

Mechanistic Insights Into The Therapeutic Potential Of Adjunctive Thymosin Beta-4 Treatment In Pseudomonas Aeruginosa-Induced Keratitis, Yuxin Wang

Wayne State University Dissertations

Tβ4, a naturally occurring 43-amino acid protein, has been found to promote wound healing and reduce corneal inflammation. Topical Tβ4 as a therapeutic agent in conjunction with ciprofloxacin improves the outcome of Pseudomonas aeruginosa-induced keratitis by regulating the cellular functions of PMNs and MΦs and enhancing the production of SPMs. Understanding the mechanisms of Tβ4 provides valuable insights and novel therapeutic potential for resolving disease pathogenesis not only in the cornea but also in other infectious and immune-regulated inflammatory conditions.

Intercontinental Comparisons Of Subterranean Host-Parasite Communities Using Bipartite Network Analyses, Altangerel Tsogtsaikhan Dursahinhan, Sebastian Botero-Cañola, Scott L. Gardner

Scott L. Gardner Publications

Rodents living in a subterranean ecotope face a unique combination of evolutionary and ecological pressures and while host species evolution may be driven by the selective pressure from the parasites they harbour, the parasites may be responding to the selective pressures of the host. Here we obtained all available subterranean rodent host-parasite records from the literature and integrated these data by utilizing a bipartite network analysis to determine multiple critical parameters to quantify and measure the structure and interactions of the organisms present in host-parasite communities. A total of 163 species of subterranean rodent hosts, 174 parasite species, and 282 …

Host-Genetic-Based Outcome Of Co-Infection By Pcv2b And Prrsv In Pigs, Christian W. Eaton, Hiep Vu, Arabella L. Hodges, Seth P. Harris, Stephen D. Kachman, Daniel C. Ciobanu

School of Veterinary and Biomedical Sciences: Faculty Publications

Replication of porcine circovirus type 2 (PCV2), an important worldwide swine pathogen, has been demonstrated to be influenced by host genotype. Specifically, a missense DNA polymorphism (SYNGR2 p.Arg63Cys) within the SYNGR2 gene was demonstrated to contribute to variation in PCV2b viral load and subsequent immune response following infection. PCV2 is known to induce immunosuppression leading to an increase in susceptibility to subsequent infections with other viral pathogens such as porcine reproductive and respiratory syndrome virus (PRRSV). In order to assess the role of SYNGR2 p.Arg63Cys in co-infections, pigs homozygous for the favorable SYNGR2 p.63Cys (N = 30) …

The Influence Of Decorin, A Potential Pro-Inflammatory Stimulant, On The Mechanical Properties Of The Annulus Fibrosus, Sabrina Sinopoli

Theses and Dissertations (Comprehensive)

Previous literature has investigated the biomechanical properties of various animal models, but few have studied an isolated and intact rat tail annulus fibrosus. Decorin, a class 1 small leucine-rich protein (SLRP) has the potential to trigger an inflammatory environment as previous research has shown that it may stimulate inflammation via the toll-like receptor (TLR) pathway. An increased inflammatory environment can have biomechanical implications for the disc, and so the ability of decorin to stimulate an environment that alters the mechanical properties of the disc was investigated.

The purpose of this study was to investigate the potential of decorin, a proteoglycan …

Natural Variation In Temperature-Modulated Immunity To Pseudomonas Syringae Pv. Tomato (Pst Dc3000) In Arabidopsis Thaliana Plants, Christina A. M. Rossi

Theses and Dissertations (Comprehensive)

Studies conducted on the model plant-pathogen system Arabidopsis thaliana-Pseudomonas syringae pv. tomato (Pst) showed that elevated temperature suppresses the pathogen-induced production of salicylic acid (SA), which is a key plant defence hormone. This increased host vulnerability at higher temperatures is due to downregulated expression of CALMODULIN BINDING PROTEIN 60-LIKE G (CBP60g) and SYSTEMIC ACQUIRED RESISTANCE DEFICIENT 1 (SARD1), which encode master regulators of SA production. Collectively, these previous studies only focused on one natural accession of Arabidopsis called Columbia-0 (Col-0). However, the intraspecific variation in Arabidopsis immunity phenotypes under elevated temperature remains unknown. To fill this critical knowledge gap, my …

Promiscuous Feeding Across Multiple Honey Bee Hosts Amplifies The Vectorial Capacity Of Varroa Destructor, Zachary S. Lamas, Serhat Solmaz, Eugene V. Ryabov, Joseph Mowery, Matthew Heermann, Daniel Sonenshine, Jay D. Evans, David J. Hawthorne

Biological Sciences Faculty Publications

Varroa destructor is a cosmopolitan pest and leading cause of colony loss of the European honey bee. Historically described as a competent vector of honey bee viruses, this arthropod vector is the cause of a global pandemic of Deformed wing virus, now endemic in honeybee populations in all Varroa-infested regions. Our work shows that viral spread is driven by Varroa actively switching from one adult bee to another as they feed. Assays using fluorescent microspheres were used to indicate the movement of fluids in both directions between host and vector when Varroa feed. Therefore, Varroa could be in either …

Frankenbacteriosis Targeting Interactions Between Pathogen And Symbiont To Control Infection In The Tick Vector, Lorena Mazuecos, Pilar Alberdi, Angélica Hernández-Jarguín, Marinela Contreras, Margarita Villar, Alejandro Cabezas-Cruz, Ladislav Simo, Almudena González-García, Sandra Díaz-Sánchez, Girish Neelakanta, Sarah I. Bonnet, Erol Fikrig, José De La Fuente

Biological Sciences Faculty Publications

(Summary) Tick microbiota can be targeted for the control of tick-borne diseases such as human granulocytic anaplasmosis (HGA) caused by model pathogen, Anaplasma phagocytophilum. Frankenbacteriosis is inspired by Frankenstein and defined here as paratransgenesis of tick symbiotic/commensal bacteria to mimic and compete with tick-borne pathogens. Interactions between A. phagocytophilum and symbiotic Sphingomonas identified by metaproteomics analysis in Ixodes scapularis midgut showed competition between both bacteria. Consequently, Sphingomonas was selected for frankenbacteriosis for the control of A. phagocytophilum infection and transmission. The results showed that Franken Sphingomonas producing A. phagocytophilum major surface protein 4 (MSP4) mimic pathogen and reduce infection …

Interactions Between Hiv And Opioids On Antiretroviral Accumulation, The Blood Brain Barrier, And The Inflammatory Response In The Brain., Kara Rademeyer

Theses and Dissertations

The complex mechanisms related to HIV infection, neurodegeneration, and chronic neuroinflammation collectively describe neuroHIV (Hauser et al. 2007; Chang et al. 2014; Smith et al. 2014). Specifically, opioid abuse, poor penetration of antiretroviral (ARV) drugs, chronic inflammation and neuronal injury/degeneration are all implicated in neuroHIV (Fantuzzi et al. 2003; Letendre et al. 2004; Verani et al. 2005; Duncan and Sattentau 2011; Hong and Banks 2015; Simoes and Justino 2015; Olivier et al. 2018; Murphy et al. 2019; Osborne et al. 2020). For the first time, we demonstrate that morphine, fentanyl, and methadone in vivo alter the brain accumulation of ARVs, …