Immunology and Infectious Disease Commons^™

Importance Of Specific Nk Cell Subsets For Antitumor Immunity In Hpv+ Cancers, Madison O'Hara

Dissertations & Theses (Open Access)

High-risk type human papillomaviruses (HPV) are associated with genital and oral cancers, and the incidence of HPV+ head and neck squamous cell cancers is fast increasing worldwide. Survival rates for patients with locally advanced disease are poor and variable after standard of care (SOC) treatment. Identifying the antitumor host immune mediators important for treatment response and designing strategies to promote them are essential for improving clinical outcome. The natural killer (NK) cells are a critical component for antitumor innate effector immunity. Among the multitude of activation and inhibitory receptors on immune cells, HLA-DR is recognized as an important activation marker …

The Role Of B Cell Activation State And Sex In Aryl Hydrocarbon Receptor Mediated Induction Of Chemokine Receptor 9 And Alpha4beta7 Expression In Vitro, Logan Bauerle

Master's Theses

Defense of mucosal tissues from microbial infection and allergy is reliant on continual production of antibodies. The aryl hydrocarbon receptor (AhR) is known to regulate B cell development and is associated with suppression of systemic humoral immunity. Recent attention has been paid to the role of the AhR in altering expression of cell adhesion molecules (CAMs). B cells express CAMs and chemokine receptors to migrate around the body for localized secretion of antibodies. AhR agonists promote B cell migration to the small intestine through upregulation of chemokine receptor 9 (CCR9) and integrin α₄β₇. Both the AhR …

Antimicrobial Activity Of Cat Flea (Ctenocephalides Felis) Gut Proteins On Different Days After Blood Feeding, Dhruva K. Karnik

Honors College Theses

Cat fleas (Ctenocephalides felis) are a blood-feeding ectoparasitic insect and a common domestic pest found throughout the world. Because of their reliance on host blood, fleas are exposed to blood-borne pathogens; however, the flea gut lumen is a hostile environment for microbial colonization. For example, the gut epithelia differentially express immune genes in response to feeding. In the present study, we measured the antimicrobial activity of gut proteins from cat fleas at different days after feeding (2, 5, 7, and 14). Dissected flea guts were homogenized, passed through a syringe filter, and measured in a protein assay kit. …

Cultivating Excellence: A Literature Review On Harnessing The Power Of The Gut Microbiome For Athletic Performance, Maya Katharine Dean

Honors Projects

The interplay between our gut microbiome and health is immense. This literature review analyzes the current research assessing the interplay between gut microbiome and athletic performance. Knowing how to improve gut microbial diversity via nutrition and supplementation can take athletic performance to the next level; namely improvements in immune, mental, and physical health.

The Sex Chromosome Complement And Gut Microbiome Act Independently And Collaboratively To Impart Sex Dimorphisms In Humoral Immunity, Carly J. Amato-Menker

Graduate Theses, Dissertations, and Problem Reports

Sex dimorphisms in immunity are well-documented and have significant clinical implications. While the immunomodulatory effects of sex hormones have been extensively documented, recent recognition of the nuanced contributions of the sex chromosome complement (XX vs. XY) and the gut microbiome to immune sex dimorphisms underscores the need for a more comprehensive understanding. Within this context, the work herein focuses on unraveling the individual and collaborative impacts of the sex chromosome complement and gut microbiota on humoral immune activation. We assessed humoral immune responses to immunization with heat-killed Streptococcus pneumoniae (HKSP) in Four Core Genotype (FCG) mice and found elevated IgM-secreting …

The Influence Of Intracellular Photosymbiosis On The Evolution And Function Of Cnidarian Immunity, Madison A. Emery

Biology Dissertations

Intracellular photosymbiosis with Symbiodiniaceae is facilitated by cnidarian immunity as it is required for symbiont recognition and is subsequently suppressed to maintain stable intracellular symbiosis. To date, it is unclear how the cnidarian-Symbiodiniaceae symbiosis influences immune gene repertoires, immune gene expression, and disease pathology across its independent evolutions. To address these knowledge gaps, my dissertation approaches studying the cnidarian-Symbiodiniaceae symbiosis through a comparative lens to determine how it shapes immune gene evolution and immune responses in divergent symbiotic cnidarian species. In chapter two I survey eight non-symbiotic and seven symbiotic cnidarians proteomes for four families of pattern recognition receptors (PRRs) …

The Characterization Of Vig-1’S Expression Patterns In Ipnv-Infected, Or Dsrna-Treated, Rainbow Trout Cells, Samantha Lum

Theses and Dissertations (Comprehensive)

In Canada, annual trout production is valued at over $60M with approximately 10,000 tonnes of trout produced per year. Rainbow trout (Oncorhynchus mykiss) are one of the most commonly farmed fresh-water fish in Canada. The high-density farming practices involved in aquaculture increase rainbow trout susceptibility to aquatic viruses such as infectious pancreatic necrosis virus (IPNV). The innate antiviral immune response in rainbow trout is poorly characterized, and the functions of numerous interferon stimulated genes (ISG) in rainbow trout remain unclear. One such gene, virus-induced gene 1 (vig-1) has been poorly studied; however, the human orthologue for vig-1 …

Immune Outcomes Affected By Selection For Parasite Resistance In Katahdin Sheep, Kelsey Lynne Bentley

Graduate Theses, Dissertations, and Problem Reports

Our understanding of the complex connection between selection for parasite resistance and the overall health outcomes in livestock is unclear. This study investigates the impact of post-weaning fecal egg count (PFEC) estimated breeding values (EBV) on health outcomes and immune responses in Katahdin sheep. Selection for PFEC, favoring Low-PFEC lambs, not only affects survivability to weaning but also suggests broader implications for immunity beyond parasite resistance. The effect of PFEC EBV on antibody production in response to vaccination against Clostridium perfringens type C&D and tetanus toxoid (CD&T) revealed a stepwise decrease in immunoglobin (IgG) from Low-PFEC to High-PFEC groups upon …

Effect Of Macrophage Expressed Α7 Nicotinic Acetylcholine Receptor (Α7nachr) On Migration Of Macrophages During Inflammation, Kasey Keever

Electronic Theses and Dissertations

Sepsis is a life-threatening condition characterized by overwhelming inflammation, resulting in organ system damage, leading to a high mortality rate. Care in the clinical setting is supportive, and there are no approved sepsis-specific treatments. In septic mice, activation of the cholinergic anti-inflammatory pathway decreases cytokine secretion by leukocytes and improves survival. The cholinergic anti-inflammatory pathway is a reflex of the parasympathetic nervous system, converging on the α7 nicotinic acetylcholine (α7nAChR) at the surface of macrophages. Signaling through the receptor blocks NF-kB activation, thus cytokine secretion. Receptor activation has other effects on macrophages, including modulating their migration to …

The Role Of The Mek1/2-Erk-Rsk Signalling Axis In Innate Immune Memory, Rachel Low

Electronic Thesis and Dissertation Repository

Macrophages are innate immune cells that change their cellular states in response to different stimuli. This process is referred to as “innate immune memory” which can render two polarizing states: hyporesponsive (tolerated) or hyperresponsive (trained) states. To date, epigenetic modifications were shown to play a key role in innate immune memory. However, the signalling that induces memory is poorly understood. In this study, I examined the effects of various inhibitors targeting key signalling molecules involved in the activation of macrophages by the Gram-negative cell wall component lipopolysaccharide. I found that prolonged inhibition of the MEK1/2-ERK-RSK signalling axis prevented tolerance and …

Evaluating The Role Of The Bovine Vaginal Microbiome In Neonatal And Maternal Health Outcomes, Riley D. Messman

Theses and Dissertations

The dam vaginal microbiota is the first major microbial inoculating community within the neonate. The composition of the dam vaginal microbiota has implications in calf commensal microbiota development. Alterations of the dam microbial community prior to parturition could alter inoculating communities and immune responses in both the dam and calf. Thus, authors aimed to elucidate the microbial community composition of the bovine dam vaginal and calf nasal microbiota post-partum after utilizing betadine lavages (BL). The dam vaginal and calf nasal microbial communities and immune responses were evaluated at 0-, 15-, 30- and 60-day post-partum. Microbiota composition of the dam haircoat, …

The Role Of Lkb1 Spliceoforms In Itreg-Th17 Plasticity And Their Interactions With Pkcθ And Sirt1 Downstream Of Il-6 Signaling, Deeksha Mohan

Doctoral Dissertations

Following activation, CD4 T cells undergo metabolic and transcriptional changes as they respond to external cues and differentiate into T helper (Th) cells. T cells exhibit plasticity between Th phenotypes in highly inflammatory environments, such as colitis, in which high levels of IL-6 promote plasticity between regulatory T (Treg) cells and Th17 cells. Protein Kinase C theta (PKCθ) is a T cell-specific serine/threonine kinase that promotes Th17 differentiation while negatively regulating Treg differentiation. Liver kinase B1 (LKB1), also a serine/threonine kinase and encoded by Stk11, is necessary for Treg survival and function. Stk11 can be alternatively spliced to produce a …

Investigating The Distinct Role Of Pd-L2 In Modulating Human T Cells Responses, Anupallavi Srinivasamani

Dissertations & Theses (Open Access)

INVESTIGATING THE DISTINCT ROLE OF PD-L2 IN MODULATING HUMAN T CELL RESPONSES

Anupallavi Srinivasamani, M.S.

Advisory Professor: Michael A. Curran, Ph.D.

Therapeutic blockade of the Programmed cell death-1 (PD-1) receptor and its ligand Programmed death ligand-1 (PD-L1) has revolutionized the treatment of multiple cancers and made durable tumor regression a possibility in the clinic. PD-1 blockade prolonged progression-free survival and overall survival with lesser high-grade toxicity in patients with advanced melanoma when compared to the other FDA-approved checkpoint blockade target, CTLA-4. Unlike CTLA-4, PD-1 is unique in its ability to regulate T cell functions in lymphoid tissues as well as …

Characterization Of The Immunoglobulin Lambda Chain Across Diverse Human Populations., William Gibson

Electronic Theses and Dissertations

The adaptive immune system relies on a diverse set of over one hundred immunoglobulin (IG) genes across three genomic loci that are variably combined to form antibodies (Ab). The IG Lambda locus is one of two loci which encodes the IG light chain. The complexity of the IGL locus severely limits the effective use of standard short-read sequencing, limiting our knowledge of population diversity in these loci. We leveraged single molecule real-time (SMRT) long-read sequencing in conjunction with IGL-targeted DNA capture to develop the method IG-Cap for accurate and high-throughput sequencing of the IGL locus. We benchmarked this method using …

Effects Of 11-Kt And Prolactin On Gene Expression, Parental Care Behaviour And Immune Response In Male Bluegill Sunfish., Adriano A P Da Cunha

Electronic Thesis and Dissertation Repository

Parental care is very critical for reproduction in species that provide it. Hormones such as prolactin and androgens play a crucial role in parenting and reproductive behaviours. In mammals and birds, prolactin’s role in parental care is well-established; it stimulates milk production and stimulates attachment to newborns by its release in the preoptic area of the hypothalamus (POA), among other functions. Androgens, on the other hand, are commonly associated with male secondary sex characteristics, territoriality, and aggressiveness in mammals and birds. There are similar reports of prolactin and androgen effects in fish, but there are fewer studies. I investigated if …

Novel Natural Compounds Derived From Tcm In The Treatment Of Food Induced Anaphylaxis, Ibrahim Musa

NYMC Student Theses and Dissertations

Food allergy is a highly prevalent disease affecting about 30 million people in the U.S. It is managed primarily by food avoidance due to lack of promising treatment options. ASHMI (anti-asthma herbal intervention) which consists of three components, Sophorae flavescentis, Ganoderma lucidum, Glycyrrhiza uralensis has been shown to inhibit allergic lung inflammation in antigen sensitized and challenged mice. In this study we isolate and identify the active compound in Sophorae flavescentis, characterized the mechanism of IgE inhibitory effect, biomarkers and potential to prevent food anaphylaxis.

To separate and identify the compounds we used column chromatography, high-performance liquid chromatography, mass …

Effects Of Cyclic Heat Stress On The Acute Inflammatory Response In Broilers, Alessandro J. Rocchi

Poultry Science Undergraduate Honors Theses

Heat stress (HS) is a growing concern in broiler production due to increasing environmental temperatures. Little is known of the overall effect of HS on innate immunity. Lipopolysaccharide (LPS), an outer membrane component of Gram-negative bacteria, is commonly used to study the inflammatory response. In avian species, the local tissue and systemic inflammatory activities in response to LPS may be determined concurrently, over time, in an individual, using the growing feather (GF) pulp dermal test along with blood measurements (dual-window approach). To examine the effect of cyclic HS on the local and systemic acute inflammatory responses, Cobb 500 male broiler …

Adipocytes And Innate Immunity In Systemic Sclerosis, Nancy Wareing

Dissertations & Theses (Open Access)

Systemic sclerosis (SSc; scleroderma) is a chronic systemic autoimmune and connective tissue disorder characterized by vasculopathy, autoimmune phenomena, and widespread fibrosis. Skin thickening and tightening is the cardinal feature of SSc and is responsible, in part, for the considerable morbidity of this disease. There are currently no targeted treatments for skin manifestations in SSc, primarily due to our fragmented understanding of its pathophysiologic mechanisms. In PART I, we report a previously unappreciated link between aberrant expression of the developmental gene sine oculis homeobox homolog 1 (SIX1) in skin-associated adipocytes in SSc skin and the early loss of dermal white adipose …

Tgf-B Signaling Mechanisms In Caenorhabditis Elegans Response To Bacterial Pathogens, Emma J. Ciccarelli

Dissertations, Theses, and Capstone Projects

When exposed to infection, the nematode C. elegans mounts an innate immune response through secretion of antimicrobial peptides (AMPs). Different signaling pathways in the worm regulate release of these AMPs. One highly conserved pathway is the C. elegans BMP like pathway – regulated by the ligand DBL-1. The DBL-1 pathway is noted for its significant role in development but has also been shown to regulate many post-developmental processes within the worm, including the immune response. We are interested in determining how DBL-1 signaling can mediate a response specific to immunity, separate from its other functions in the worm. Through survival …

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

Doctoral Dissertations

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

The Impacts Of Immune Challenges On Fish Behavior And Physiology, Teisha King

LSU Doctoral Dissertations

For species living in dominance hierarchies, social rank dictates access to resources and often contributes to reproductive success. To ensure survival, individuals constantly evaluate trade- offs between crucial biological systems, like the reproductive and immune systems, depending on their social rank and physiological state. Little is known about how social species balance interactions between immune system function, fluctuations in social status and reproductive fitness, and the performance of behaviors necessary for maintaining social status when sick, particularly in fishes, the largest and most diverse group of vertebrates. My dissertation research uses a whole animal approach to examine how physiological profiles …

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 …

Sex-Dependent Effects Of Induced Acute Inflammation On Glucose Homeostasis And Rna Editing Enzymes, Christian A. Rivas

MSU Graduate Theses

The first line of defense against bodily insults, like pathogen invasion, is the innate immune system. Innate immunity sets in motion countless cascades that result in inflammation. Inflammation simultaneously affects multiple biological processes like metabolism and gene expression. Males and females react differently to inflammation. To understand both molecular and physiological sex differences in inflammation, we examined how inflammation affects gene expression and glucose metabolism. Adenosine deaminase acting on RNA (ADAR1) is upregulated by inflammation and catalyzes RNA editing, a process where nucleotides encoded by the genome are modified. ADAR1 also controls the innate immune reaction by decreasing activity of …

Cluster Homolog Of Immunoglobulin-Like Receptor Genes In Chicken Immune Responses, Brandi A. Sparling

Graduate Theses, Dissertations, and Problem Reports

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 …

Tissue And Sex-Dependent Regulation Of Innate Immunity And Rna Editing In Mice, Kelsey R. Kendrick

MSU Graduate Theses

Inflammation occurs as a result of insult or infection within the body. Individual cells respond to inflammation by upregulating genes that help mediate the immune response, such as ADAR1. ADAR1 helps regulate the immune response but also catalyzes a process called RNA editing. RNA editing alters the sequence of select mRNAs to alter the encoded proteins. The result is altered function of the encoded protein, which is often beneficial for the cell. Our goal was to determine how inflammation affects the function of ADAR1. Since we know that the effects of inflammation vary between different organs and sexes, we examined …

Characterizing The Function Of B Cells That Accumulate In The Inflamed Central Nervous System In Anti-Myelin Autoimmunity, Lika Chowdhury

Electronic Thesis and Dissertation Repository

While the role of autoimmune T cells has been extensively studied in anti-myelin

autoimmunity, little is known about the function of B cells in multiple sclerosis (MS), a chronic inflammatory disease of the central nervous system (CNS). B cells form clusters with T cells in the meninges directly adjacent to demyelinating lesions. Previous studies have shown that disease progression is dependent on the depletion of specific populations of B cells, but it is not clear which contributes to pathology or how. The purpose of this thesis is to characterize the population of meningeal B cells to determine how they differ …

A Novel Transmembrane Ligand Inhibits T Cell Receptor Activation, Yujie Ye

Doctoral Dissertations

T lymphocytes (T cells) play essential roles in the adaptive immune system. Each mature T cell expresses one type of functional T cell receptor (TCR). The TCR recognizes antigens bound to the major histocompatibility complex (MHC) in antigen presenting cells. The resulting stimulation signal crosses the transmembrane domain of TCR and initiates downstream signaling cascades. The human immune system relies on TCRs to recognize a variety of pathogens. Normally, TCR can distinguish the self-antigens from pathogenic antigens. However, dysfunction or aberrant expression of TCRs causes different inflammatory and autoimmune diseases, which afflict millions of people annually (Chapter I). Current treatments …

Doxorubicin-Induced Cardiotoxicity Is Mediated By Neutrophils Through Release Of Neutrophil Elastase, Anchit Bhagat

Dissertations & Theses (Open Access)

Doxorubicin (Dox) is one of the most effective chemotherapy agents that is used for the treatment of childhood cancer. Unfortunately Dox treatment can cause damage to the heart. Indeed, childhood cancer survivors are at a higher risk of developing a cardiovascular disease at an earlier age. The mechanisms by which Dox causes acute and late cardiotoxicity are not completely understood. One understudied area in Dox-induced cardiotoxicity is the contribution of inflammation and innate immune cells, in particular neutrophils. Recognizing that neutrophils have been implicated in a number of heart diseases, we evaluated the role of neutrophils in Dox-induced cardiotoxicity. Here, …

Comparison Of The Humoral Immune Response Following Both Bacterial Challenge And Rnai Of Major Factors On Proliferation Of Bartonella Quintana In The Human Louse, Jake Zina

Masters Theses

Human body lice, Pediculus humanus humanus, and head lice, Pediculus humanus capitis, have been hematophagous ectoparasites of humans for thousands of years. Despite being ecotypes, only body lice are known to transmit bacterial diseases to humans, and it appears that lower humoral and cellular immune responses allow body lice to possess a higher vector competence. We previously observed that the transcription level of the defensin 1 gene was up-regulated only in head lice following oral challenge of Bartonella quintana, a causative agent of trench fever, and also that body lice excreted more viable B. quintana in their …

Chemical Biology Approaches For Tracking And Manipulation Of Macrophage Phenotypes, Javier A. Mas Rosario

Doctoral Dissertations

Macrophages are white blood cells of the innate immune system that have the ability to change phenotypically depending on the stimuli present in their surroundings through a process commonly referred to as polarization. Macrophage phenotypes broadly range from pro-inflammatory, anti-tumor (M1) to immune-suppressing (M2). Of particular interest to this work, breast cancer progression and metastasis rely on the presence of M2-like tumor-associated macrophages (TAMs). While many studies have shown the involvement of macrophages in tumor progression and metastasis, there remains a need to further explore these interactions and the polarization process, including tracking of macrophage subtypes. Toward this end, I …