Immunity Commons^™

The Association Between Aerobic Exercise And Changes In Hdl Quality Induced By Egg Consumption – A Post-Hoc Analysis Of A Randomized, Controlled, Crossover Dietary Intervention Study, Rachael Woodruff, Catherine J. Andersen

Honors Scholar Theses

Abstract

Objective: Daily intake of whole eggs and aerobic exercise have independently been shown to increase high-density lipoprotein cholesterol (HDL-C) and measures of HDL function, suggesting cardioprotective effects of these lifestyle interventions. However, it is unknown whether exercise volume can synergistically or differentially impact diet responses and egg effects on HDL. Therefore, we evaluated whether exercise volume was associated with distinct effects of consuming different egg-based diets on measures of HDL size, function, and composition.

Methods: Twenty-six healthy men and women completed a 16-week randomized, controlled, crossover intervention study which aimed to investigate the effects of egg-free, egg-white, and whole-egg …

Mismatch Repair Deficient Neoantigen And Associated Circulating T-Cell Receptor Repertoires In Lynch Syndrome, Ana Bolivar

Dissertations and Theses (Open Access)

Lynch Syndrome (LS) is the most common inherited colorectal cancer (CRC) syndrome. It constitutes the perfect model to understand DNA mismatch repair deficient (MMRd) carcinogenesis, which underlies 15% of early-stage CRC. LS patients develop MMRd tumors with high loads of shared neoantigens (neoAgs), which are recognized by the immune system. Previous research has concentrated on discovering neoAgs and their potential as targets for vaccines in LS patients. However, these studies have primarily identified shared neoAgs from cancers, lacking detailed information on targetable neoAgs present in precancerous lesions. Understanding this landscape of pre-cancer derived neoAgs is crucial for intercepting cancer development …

The Role Of Oncomodulin In The Central Nervous System Inflammation, Evan Paltjon

Honors Theses

Acoustic overexposure in mice leads to an excess of calcium influx in outer hair cells (OHCs) and causes permanent hearing loss due to death of OHCs. Oncomodulin is a parvalbumin calcium buffering protein located in OHCs of the cochlea. Early pilot studies indicate that genetic deletion of OCM results in immune-related pathology throughout the cochlea. Why and how this occurs is unknown. Studies in wild type (WT) and OCM knockout (KO) mice demonstrate greater numbers of immune cells are associated with noise exposure in an OCM knockout than in WT. Expression of toll-like receptor 4 (TLR4) leads to the recruitment …

Hierarchal Single-Cell Lineage Tracing Reveals Differential Fate Commitment Of Cd8 T-Cell Clones In Response To Acute Infection., Leena Abdullah

Dartmouth College Ph.D Dissertations

Generating balanced populations of CD8 effector and memory T cells is necessary for immediate and durable immunity to infections and cancer. Yet, a definitive understanding of CD8 differentiation remains unclear. Here we used CARLIN, a processive lineage recording mouse model with single-cell RNA-seq and TCR-seq to track endogenous antigen-specific CD8 T cells during acute viral infection.

Transcriptional profiling of antigen-specific T cells at the peak of the effector response to Vesicular stomatitis virus uncovered a diverse repertoire of expanded antigen-specific T-cell clones represented by seven transcriptional states. TCR enrichment analysis identified TCR clones with differential memory- or effector-fate biases during …

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

Dissertations and 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 …

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.

Regulation And Therapeutic Targeting Of Virus-Specific Resident Memory T Cells, Jordan Fredriksen Isaacs

Dartmouth College Ph.D Dissertations

CD8+ T cells are critical to the immune response to pathogens, as they kill infected cells and generate immunologic memory. Following infection, antigen-specific T cells expand approximately 10,000-fold and migrate to sites of inflammation in order to clear the pathogen. Once infection is resolved, a small pool of memory T cells persist in circulation and within tissues ready to respond rapidly upon re-exposure. Given the importance of CD8+ T cells, significant efforts have been made over the years to better understand how different memory T cell subsets are established, maintained, and regulated. The most recently identified subset, resident memory T …

Heterogeneity And Plasticity Of The Naïve Cd4+ T Cell Compartment, Alia Sajani

Dartmouth College Ph.D Dissertations

Recent studies have illuminated unexpected heterogeneity in the naïve T cell compartment. Using single cell RNA sequencing of mouse naïve CD4⁺ T cells, we identified 5 unique transcriptional subsets within the naïve CD4⁺ T cell compartment. These include a quiescence cluster (T^Q) marked by Klf2, Klf6, Jun and Btg2, a memory-like cluster (T^MEM) marked by Ccr7, Il7r and Tcf7, a TCR reactive cluster (T^TCR) marked by Cd5, Cd6 and Nr4a1, an IFN responsive cluster (T^IFN) marked by Stat1, Irf7 and Ifit1 and …

The Conceptual Foundations Of Innate Immunity: Taking Stock 30 Years Later, Thomas Pradeu, Bart P.H.J. Thomma, Stephen E. Girardin, Bruno Lemaitre

Presidential Fellows Articles and Research

While largely neglected over decades during which adaptive immunity captured most of the attention, innate immune mechanisms have now become central to our understanding of immunology. Innate immunity provides the first barrier to infection in vertebrates, and it is the sole mechanism of host defense in invertebrates and plants. Innate immunity also plays a critical role in maintaining homeostasis, shaping the microbiota, and in disease contexts such as cancer, neurodegeneration, metabolic syndromes, and aging. The emergence of the field of innate immunity has led to an expanded view of the immune system, which is no longer restricted to vertebrates and …

Large-Scale Phenotyping Of Patients With Long Covid Post-Hospitalization Reveals Mechanistic Subtypes Of Disease, Felicity Liew, Claudia Efstathiou, Sara Fontanella, Matthew Richardson, Ruth Saunders, Dawid Swieboda, Jasmin K Sidhu, Stephanie Ascough, Shona C Moore, Noura Mohamed, Jose Nunag, Clara King, Olivia C Leavy, Omer Elneima, Hamish J C Mcauley, Aarti Shikotra, Amisha Singapuri, Marco Sereno, Victoria C Harris, Linzy Houchen-Wolloff, Neil J Greening, Nazir I Lone, Matthew Thorpe, A A Roger Thompson, Sarah L Rowland-Jones, Annemarie B Docherty, James D Chalmers, Ling-Pei Ho, Alexander Horsley, Betty Raman, Krisnah Poinasamy, Michael Marks, Onn Min Kon, Luke S Howard, Daniel G Wootton, Jennifer K Quint, Thushan I De Silva, Antonia Ho, Christopher Chiu, Ewen M Harrison, William Greenhalf, J Kenneth Baillie, Malcolm G Semple, Lance Turtle, Rachael A Evans, Louise V Wain, Christopher Brightling, Ryan S Thwaites, Peter J M Openshaw, Phosp-Covid Collaborative Group, Isaric Investigators

Faculty, Staff and Student Publications

One in ten severe acute respiratory syndrome coronavirus 2 infections result in prolonged symptoms termed long coronavirus disease (COVID), yet disease phenotypes and mechanisms are poorly understood1. Here we profiled 368 plasma proteins in 657 participants ≥3 months following hospitalization. Of these, 426 had at least one long COVID symptom and 233 had fully recovered. Elevated markers of myeloid inflammation and complement activation were associated with long COVID. IL-1R2, MATN2 and COLEC12 were associated with cardiorespiratory symptoms, fatigue and anxiety/depression; MATN2, CSF3 and C1QA were elevated in gastrointestinal symptoms and C1QA was elevated in cognitive impairment. Additional markers …

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

Biology Dissertations - Archive

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) …

Revolutionizing Our Understanding Of Specific Platelet-Pathogen Interactions, Hammodah Rawhi Hammodah Alfar

Theses and Dissertations--Molecular and Cellular Biochemistry

Aside from their classical role in maintaining hemostasis, platelets are considered first-line vascular guardians that influence both the innate and adaptive immune systems. This is mediated by either direct interactions with immune cells or through the release of pre-stored cytokines and chemokines upon interacting with pathogens such as viruses. While this establishes platelets as potential players in the response to pathogens, it remains unclear what platelets can do with pathogens and how important that is to immune responses, especially against viruses. Most systemic viremias, such as HIV-1, present with mild thrombocytopenia, which is mediated through several mechanisms such as a …

Coral Scar Investigation: An Application Of Machine Learning And Computational Biology Methods To Understand Coral Holobiont Response To Various Tissue Loss Diseases, Emily W. Van Buren

Biology Dissertations - Archive

Coral disease is one of the biggest challenges facing coral reefs that actively changes biodiversity resulting in coral decline. With the rising threat of diseases, corals require biomarkers that reflect the immune systems and differences between common coral tissue loss diseases to best assist in coral restoration efforts. To obtain these biomarkers, my dissertation leverages two previously published datasets from two tissue loss disease exposure studies to investigate genes that are relevant for coral immune pathways, disease susceptibility, and classification between the diseases. In Chapter 2, I use comparative computational biology tools and protein assays to identify the melanin cascade …

Effects Of Pancreatic Amylin On The Peripheral And Cns Immune Response In A Model Of Type-2 Diabetic Brain Injury, Edric Da'shon Winford

Theses and Dissertations--Neuroscience

Type-2 diabetes (T2D) is a metabolic disorder that increases the risk for cerebrovascular disease and dementia and is associated with the progression of Alzheimer's Disease; however, the mechanisms responsible for T2D-associated dementia are still poorly understood. T2D leads to alterations of the innate and adaptive immune response that contribute to its progression, but how these cells contribute to cognitive decline during T2D is unknown. As there are no approved therapeutics for T2D that modulate the immune response, it is important that we investigate how peripheral immune cells contribute to cognitive decline during T2D. Amylin is an amyloidogenic hormone synthesized and …

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

Graduate Theses, Dissertations, and Problem Reports (ETD)

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 …

Terminally Differentiated Effector Memory T Cells Associate With Cognitive And Ad-Related Biomarkers In An Aging-Based Community Cohort, Edric Winford, Jenny Lutshumba, Barbara J. Martin, Donna M. Wilcock, Gregory A. Jicha, Barbara S. Nikolajczyk, Ann M. Stowe, Adam D. Bachstetter

Markey Cancer Center Faculty Publications

Background and purpose: The immune response changes during aging and the progression of Alzheimer’s disease (AD) and related dementia (ADRD). Terminally differentiated effector memory T cells (called TEMRA) are important during aging and AD due to their cytotoxic phenotype and association with cognitive decline. However, it is not clear if the changes seen in TEMRAs are specific to AD-related cognitive decline specifically or are more generally correlated with cognitive decline. This study aimed to examine whether TEMRAs are associated with cognition and plasma biomarkers of AD, neurodegeneration, and neuroinflammation in a community-based cohort of older adults.

Methods: Study participants from …

Case Report: P40phox Deficiency Underlying Pediatric-Onset Systemic Lupus Erythematosus, Alejandro Nieto-Patlán, Natalia S Fernández Dávila, Yuqing Wang, Michelle Zelnick, Eyal Muscal, Martha Curry, James R Lupski, Steven M Holland, Bo Yuan, Douglas B Kuhns, Tiphanie P Vogel, Ivan K Chinn

Faculty, Staff and Students Publications

Introduction

Systemic lupus erythematosus is a multi-faceted autoimmune disorder of complex etiology. Pre-pubertal onset of pediatric systemic lupus erythematosus (pSLE) is uncommon and should raise suspicion for a genetic driver of disease. Autosomal recessive p40^phox deficiency is a rare immunologic disorder characterized by defective but not abolished NADPH oxidase activity with residual production of reactive oxygen species (ROS) by phagocytic cells.

Case presentation

We report the case of a now 18-year-old female with pSLE onset at 7 years of age. She presented with recurrent fever and malar rash. Aspects of her immune dysregulation over time have included typical pSLE …

Atm-/-Ung-/- Mice Present Reduced Levels Of Switched Immunoglobulin Isotypes Igg1 And Igg3, Lyric M. Haughton

Dissertations and Theses

B cells excise and recombine the immunoglobulin heavy chain gene locus during class switch recombination (CSR). CSR is mediated by activation induced cytidine deaminase (AID) and results in a new immunoglobulin isotype that B cells will secrete and present. AID produces mutations that convert cytosines to uracils within the intronic switch regions that precede and follow the target immunoglobulin isotype coding sequence. To resolve the mutations, B cells conduct either base excision repair (BER) or mismatch repair (MMR). Inactivating genetic mutations in BER or MMR reduce CSR. For example, a knock-out of uracil DNA glycosylase (UNG) causes a 50% reduction …

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 (ETD)

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 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 …

Sars-Cov-2 Immunogenicity Models Inform Novel Strategies That Can Improve Mrna Vaccines, Katherine S. Lee

Graduate Theses, Dissertations, and Problem Reports (ETD)

The onset of the 2020 COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, issued a call to action in the fields of biomedical science and public health to implement strategies to contain and protect against the viral threat. In record times, pharmaceutical companies produced antiviral therapies and novel mRNA vaccines that were approved by the FDA for human use. With time, these vaccines were able to assist in ending the pandemic. However, time also showed the limits of mRNA vaccine induced immunity. Despite antibody responses being initially robust, titers dramatically wane with time and are limited in cross-neutralizing ability. As …

Elucidating Mechanisms Of Enhanced Dsrna-Nanophytoglycogen Innate Immune Responses In Healthy Human Cells, Nicholas Jadaa

Theses and Dissertations (Comprehensive)

Immunostimulatory nucleic acids, such as long double-stranded RNA (ds)RNA, can stimulate innate immune responses in a non-sequence specific manner. These molecules are recognized by pattern-recognition receptors in the cytoplasm, endosome, and on the cell surface. Activation leads to the production of mediators of innate immune pathways, including type I interferon and proinflammatory cytokines. Although these receptors are present in all cells, their role in non-immune cells is often overlooked due to their lower level of responsiveness. Nanocarriers can enhance these nucleic acid-mediated responses, allowing for exploration of innate immune pathways in non-immune cells. Nanoparticles as carriers of nucleic acids can …

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 …

Sars-Cov-2: Tale Of A Microscopic Murderer, Josiah P. Garner

Quest

Independent Study

Research in progress for BIOL1406: Biology for Science Majors I

Faculty Mentor: Amina Tassa, Ph.D.

I am delighted to introduce Josiah Garner’s “SARS-CoV-2: Tale of a Microscopic Murderer.” This independent study assignment explores the impact of a novel, deadly, and worldwide virus. The assignment also examines the fast development of vaccines to control the spread and reduce the symptoms of the virus.

Josiah’s paper focuses on the early history of the emergence of COVID-19, the world response, and vaccine development. He demonstrates critical thinking skills and effectively utilizes various research methods to obtain and communicate his information. Josiah …

Molecular Mechanisms Governing The Generation Of Tissue Resident Memory Cd8 T Cells In The Setting Of Cancer, Nikhil Khatwani

Dartmouth College Ph.D Dissertations

Although there has been extensive research on T-cell responses to cancer immunotherapy, the understanding of long-lasting memory in visceral organs remains less well understood. Among these, a population of Trm cells was discovered that reside durably within tumor draining lymph nodes (TDLN) and plays a crucial role in protecting against invading melanoma cells, uncovering a new role for Trm cells at critical metastatic sites. However, little is known about the molecular mechanisms promoting Trm establishment in tissues where cancer can develop and metastasize. Here, employing longitudinal T cell receptor (TCR)-lineage-tracing and single-cell transcriptomics, we find that TDLN contain Teff cells …

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, …

Multiphasic Molecular Mechanisms Regulate Expression Of Interleukin 1Β, As Well As Other Immediate-Early Genes, In Monocytes And Macrophages, David Macar

Electronic Theses and Dissertations

Interleukin 1β (IL-1β), an important cytokine in both health and disease, functions as a major proinflammatory mediator of pathological challenges, including involvement in the cytokine storm associated with Macrophage Activation Syndrome, Hemophagocytic Lymphohistiocytosis and the severe secondary effects of SARS-CoV-2 infection. Therapeutic approaches to limiting the effects of IL-1β protein have focused either on specific protein neutralization before release from activated macrophages (by general metabolic inhibitors and inflammasome inhibition) or after release by ligand and receptor obstruction (e.g., Canakinumab, Anakinra and Rilonacept). Although these approaches are efficacious, they inhibit steps after gene expression. Since a single gene expresses …

Functional Analysis Of Two Campoletis Sonorensis Ichnovirus Vinnexins In Drosophila Melanogaster, Peng Zhang

All Dissertations

Campoletis sonorensis Ichnovirus (CsIV) is produced by the ichneumonid parasitoid Campoletis sonorensis (the primary host). Female parasitoid wasps restrictedly replicate viruses in their ovaries and inject them into a larval lepidopteran (secondary host) during oviposition. This symbiotic virus of C. sonorensis is essential for successful parasitization. CsIV is characterized by having a large, segmented double-stranded DNA genome with a large number of genes, many of which are associated with one of five multigene families. The CsIV vinnexin gene family is one of them and has four members, including CsIV-vnxD and CsIV-vnxG. Vinnexins are homologues of insect Innexins, which form gap …

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 …