Medicine and Health Sciences Commons^™

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 …

Rumen-Protected Methionine Supplementation Improves Lactation, Oxidative Status, And Immune Response During A Subclinical Mastitis Challenge In Lactating Dairy Cows., Anita Paz Lopez

Electronic Theses and Dissertations

Mastitis is a significant problem in the dairy industry, posing numerous challenges for dairy farmers worldwide. Mastitis refers to the inflammation of the mammary gland, primarily caused by bacterial infections. This condition affects the health and well-being of dairy cows and has severe economic implications for farmers and overall dairy production. The prevalence of mastitis substantially threatens milk quality, productivity, and profitability, making it a top concern in the dairy industry. Preventing mastitis in cows is crucial for maintaining the herd's health and ensuring highquality milk production. Nutritional strategies have recently gained greater attention due to a direct impact on …

The Walking Well: Effects Of Hypothalamic Amenorrhea On Athletic Performance, Annalise H. Lau

Doctor of Medical Science (DMSc)

Hormonal balance and normal menstrual cycles are key factors in athletic performance. Unfortunately, female athletes themselves are often under the impression that a lighter weight will improve their performance. Even many healthcare providers do not emphasize or are unaware of the health consequences of prolonged irregular menstruation. The main purpose of this article is to review the health consequences hypothalamic amenorrhea has on female athletes and to provide education for healthcare providers regarding the importance of recovery. A literature search was conducted utilizing PubMed, Scopus, PLOS One and EBSCO. The following keywords were input into the search bar: hypothalamic amenorrhea, …

Modeling Of Cns Cancer With A Focus On The Immune Component, Daniel Zamler

Dissertations & Theses (Open Access)

The knowledge surrounding cancers of the central nervous system remains poorly developed, in particular with regard to the immune component. The works contained in this thesis look at craniopharyngioma, glioblastoma, and several forms of brain metastasis. While some attention is given to the tumor cells themselves, as well as the patient setting which these studies model, the immune component of disease progression and treatment plays a strong role in each and is the primary focus of the works contained.

Craniopharyngioma is a relatively rare tumor in adults. Although histologically benign, it can be locally aggressive and may require additional therapeutic …

Testing For Transferred Immunity Of A Universal Influenza Vaccine In Pigs, Rachel Marie Sestak

Honors Thesis

Influenza causes high numbers of illnesses and deaths annually (CDC, 2020). Influenza vaccines prevent these complications by reducing the risk of flu illness between 40-60% (CDC, 2021). However, no vaccination exists for infants under six months old so other methods, such as passive immunity, must be explored. To determine how infants can be protected, we tested the passive transfer of a universal influenza vaccine using a pig model and researched the mechanism of transfer. Four pregnant pigs were vaccinated one time with PBS and one time with HA-129 vaccine and four were vaccinated twice with the HA-129 vaccine. After farrowing, …

Testing For Transferred Immunity Of A Universal Influenza Vaccine In Pigs, Rachel Marie Sestak

Honors Thesis

Influenza causes high numbers of illnesses and deaths annually (CDC, 2020). Influenza vaccines prevent these complications by reducing the risk of flu illness between 40-60% (CDC, 2021). However, no vaccination exists for infants under six months old so other methods, such as passive immunity, must be explored. To determine how infants can be protected, we tested the passive transfer of a universal influenza vaccine using a pig model and researched the mechanism of transfer. Four pregnant pigs were vaccinated one time with PBS and one time with HA-129 vaccine and four were vaccinated twice with the HA-129 vaccine. After farrowing, …

The Investigations Of Nps Modulated Immunity And Immunometabolism, Brittney Leigh Ruedlinger

Biomedical Sciences Theses & Dissertations

Cancers remain in the top noncommunicable diseases responsible for premature mortality. The heterogeneity among cancers and within tumors makes treating them ever more challenging. Our misfortune for developing cures is mocked by cancer, with the lowest probability of success (PoS) through clinical trials and FDA approval. At the basic level, there are generally two broad gaps impeding cancer eradication: the unidentified shared mechanism(s) exploited by all cancers and the therapeutic approach to intervene. Nanosecond pulse stimulation (NPS) offers a unique approach since its broad impacts intersect those often hijacked by oncogenesis. Metabolic pathways, known for dysfunctions among cancers, share a …

Characterizing The Role Of Necroptosis Of Airway Epithelial Cells In The Immune Response To Respiratory Pathogens, Ashleigh Nichole Riegler

All ETDs from UAB

Necroptosis, a programmed form of lytic cell death, is initiated by various viral and bacterial pathogens through irreparable ion dysregulation and energy depletion. This cellular damage results in the activation of the cellular kinases RIPK1 and RIPK3, consecutively, and the activation and membrane targeting of MLKL, the latter responsible for lysis. Here we have demonstrated that necroptosis of airway epithelial cells is key in the development of the adaptive immune response to asymptomatic colonization by Streptococcus pneumoniae (Spn). Briefly, necroptotic deficient animals or wildtype animals colonized with Spn lacking the necroptosis-triggering pneumolysin toxin, failed to recruit CD11c+ leukocytes to the …

The Enzymatic Function Of The Tir Domain: From Axon Degeneration To Innate Immunity, Kow Essuman

Arts & Sciences Electronic Theses and Dissertations

The Toll/Interleukin-1 Receptor (TIR) domain is an evolutionarily ancient protein domain conserved from bacteria to eukaryotes, and is an essential signaling component of innate immunity pathways. In animal innate immunity, TIR domains have primarily been described for their scaffolding function in assembling protein complexes in host defense. In plant immunity, TIR domains are key components of the intracellular Nucleotide Binding Leucine rich repeat (NLR) immune receptors that confer resistance to pathogens. These NLR receptors trigger cell death and an immune response upon activation, but their mechanism has remained elusive. In bacteria, TIR domain proteins have been suggested to function as …

Tetanus Immunity Among Adults In The Democratic Republic Of The Congo, Sue K. Gerber

Walden Dissertations and Doctoral Studies

Although tetanus is not a contagious disease, it can be deadly for people who are exposed and do

not have protective immunity against tetanus, which can be acquired only through vaccination.

Most studies on adult tetanus protective immunity are from high-income countries; limited

studies occur in Africa, and none has been reported from the Democratic Republic of the Congo

(DRC). This study sought to determine protective immunity against tetanus among adults in

DRC in relation to their age, sex, place of residence, and for women, antenatal care. The primary

purpose of this observational cross-sectional study using a nested serosurvey within …

T Cell Immunity In Pancreatic Cancer Is Undermined By Dendritic Cell Dysfunction, Samarth Hegde

Arts & Sciences Electronic Theses and Dissertations

Pancreatic cancer carries a dismal prognosis, and desperately needs viable therapeutic interventions beyond chemo-radiation. T cell-dependent immunotherapies have shown great promise in several tumor types, but have not been effective for the vast majority of pancreatic cancer patients. This is, in part, due to our limited understanding of how antigenicity of pancreatic lesions is recognized, and how adaptive immunity is overcome in this disease. We sought to study tumor-immune interactions and identify mechanisms for this immune-failure using several spontaneous and unperturbed mouse models of pancreatic adenocarcinoma. We found that early pancreatic lesions fail to elicit tumor-limiting CD4+ TH1 and CD8+ …

Modulation Of Autophagy And Senescence To Enhance The Response To Therapy In Triple Negative Breast Cancer, Liliya Tyutyunyk-Massey

Theses and Dissertations

Abstract

Although great strides have been made over the decades in development and optimization of anti-cancer therapies, even highly effective drugs often fail to completely eliminate tumors. Residual tumor cells can enter into a state of dormancy for prolonged periods of time but eventually are able to regain proliferative capacity and reemerge as chemotherapy-resistant disease. Because recurrent disease is a leading contributor to patient’s mortality, it is paramount to identify strategies for effectively destroying residual tumor cells.

Cytotoxic drugs and ionizing radiation are used as standard therapies in a variety of cancers. These modalities induce apoptosis, autophagy and senescence. Senescence …

Investigating The Effect Of Sodium Benzoate On Immune Cells And Microbial Populations In The Small Intestine Of Murine Species., Shelby Pedigo

Senior Honors Projects, 2010-2019

Dietary ingredients can influence the mucosal surface morphology and mucosal immunity of the gastrointestinal tract. Additional health concerns and behavioral changes have been attributed to the consumption of foods containing preservatives and additives. Sodium benzoate (SB) is a commonly used bacteriostatic in food and beverages. This study investigates the effects of SB on the gut bacteria and mucosal health in the gastrointestinal tract of laboratory mice. The extent of lymphocytic infiltration in intestinal villi and granular density of Paneth cells in the ileum were used as evaluators of mucosal immunity. Adult C57BL/6 mice were randomly assigned to two …

Effect Of Bacterial Superantigens On The Magnitude And Breadth Of Influenza-Specific Cd8+ T Cell Responses, Courtney Meilleur

Electronic Thesis and Dissertation Repository

Severe cases of influenza A virus (IAV) infection are often complicated by concomitant bacterial pneumonia or sepsis. Many bacterial species are capable of producing potent immunomodulators called superantigens (SAgs), which have the potential to interfere with cell-based antiviral immune mechanisms. I asked what effects bacterial SAgs have on both the magnitude and the breadth of antiviral CD8⁺ T cell (TCD8⁺) responses. Surprisingly, administration of SAgs to mice shortly before or after vaccination with IAV increased the number of primary TCD8⁺ responding to select IAV-derived epitopes. T cell receptor staining of these SAg-augmented populations revealed expression of …

Heme Peroxidase Hpx-2 Protects Caenorhabditis Elegans From Pathogens, Yi Liu

Dissertations & Theses (Open Access)

Heme-containing peroxidases are important components of innate immunity. Many of them functionally associate with NADPH oxidase (NOX)/dual oxidase (DUOX) enzymes by using the hydrogen peroxide they generate in downstream reactions. In Caenorhabditis elegans, a ShkT-containing peroxidase, SKPO-1, and the dual oxidase, BLI-3, contribute to resistance against the human pathogen Enterococcus faecalis, likely functioning in conjunction with each other. However, the exact mechanism(s) by which peroxidases and NOX/DUOXs contribute to pathogen resistance remain unclear. Here, we demonstrated that another peroxidase, HPX-2 (Heme-PeroXidase 2), is required for resistance against some, but not all pathogens. Tissue specific …

The Role Of Adam10 And Adam17 In Humoral And Type 2 Immunity, Joseph C. Lownik

Theses and Dissertations

The proper regulation of inducible costimulator (ICOS) and its ligand (ICOSL) have been shown to be essential for maintaining immune homeostasis. Loss of either protein results in defective humoral immunity, and overexpression of ICOS results in aberrant antibody production resembling lupus. How ICOSL is regulated in response to ICOS interaction is still unclear. We demonstrate that ADAM10 is the primary physiological sheddase of ICOSL in both mouse and human. Using an in vivo system in which ADAM10 is deleted only on B cells (ADAM10^B-/-), elevated levels of ICOSL were seen. This increase is also seen when ADAM10 is …

Development Of Cellular Assays To Monitor Enzymatic And Biological Activity Of Cd73: A Key Modulator Of Anti-Tumor Immune Response, Alexandra Fanuka

Graduate School of Biomedical Sciences Theses and Dissertations

Ecto-5’-nucleotidase, known as CD73, is an extracellular enzyme that converts adenosine monophosphate (AMP) to adenosine and has recently been identified as a potential drug target for cancer immunotherapy. Its immunosuppressive effects, mediated by the activity of adenosine, are associated with higher rates of tumor invasion and metastasis, as well as poorer prognoses overall in many cancer types. CD73 is often co-expressed with ectonucleoside triphosphate diphosphohydrolase-1 (CD39), which catalyzes the conversion of adenosine triphosphate (ATP) to adenosine diphosphate (ADP), and ADP to AMP on the surface of tumor cells. Dual expression further propagates immunosuppressive effects of adenosine in the tumor microenvironment. …

Quantitation Of Anti-Pythium Insidiosum Antibodies Before And After Immunotherapy In Healthy Dogs, Carmen Beatriz Arsuaga

LSU Master's Theses

Pythium insidiosum is an aquatic oomycete that causes invasive, progressive granulomatous lesions of the skin in dogs, horses, and cats, and of the gastrointestinal tract in dogs. Quantitation of anti-P. insidiosum IgG antibodies can be used in dogs to both confirm a suspected diagnosis and to monitor response to therapy. Recently, an immunotherapeutic product (IP) has been marketed for the treatment of pythiosis in dogs, horses, and people. The aim of this study was to evaluate the effect of administration of this product on anti-P. insidiosum IgG concentrations in dogs. The IP was administered to seven, healthy hound mixes on …

“Nothing But Blows”: Herman Melville And The Contagion Of Authority, Conrad Irving Brittenham

Senior Projects Spring 2016

In Chapter Thirty Six of Moby Dick, “The Quarter Deck,” captain Ahab rallies the Pequod’s crew behind his hunt for Moby Dick, met with no opposition other than from the ship's first mate, Starbuck. After heatedly bickering for some time, Ahab mentions in an aside, “Something shot from my dilated nostrils, he has inhaled it in his lungs. Starbuck now is mine; cannot oppose me now, without rebellion” (168). What follows is Starbuck’s “tacit acquiescence” to Ahab’s demands. Though it is unclear exactly what the “something” is that comes out of Ahab’s nose, it is clear that this one-track-mind captain …

Antibody-Mediated Immunity To Vibrio Cholerae At Epithelial Surfaces, Kara Jeanette Levinson

Legacy Theses & Dissertations (2009 - 2024)

Vibrio cholerae, the causative agent of the severe diarrheal disease cholera, has an estimated worldwide disease burden in the millions and remains a significant public health threat. Immunity to V. cholerae is primarily antibody-mediated and though V. cholerae colonization evokes a mucosal immune response, it is the secretory IgA (SIgA) antibodies produced against bacterial surface antigens, specifically lipopolysaccharide (LPS) that confer protective immunity. SIgA antibodies are thought to function by inhibiting colonization by cross-linking and agglutination of pathogens, thereby limiting access to the epithelium, a process known as immune exclusion. Recent studies in other enteric pathogens have demonstrated that SIgA …

Immunomodulation Of Myeloid-Derived Suppressor Cells By Particulate B-Glucan In Cancer., Sabrin Husein Albeituni

Electronic Theses and Dissertations

Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of immature myeloid cells that promote tumor progression. In this study, we investigated the effect of dectin-1 stimulation by yeast-derived particulate β-glucan in MDSC function and differentiation in cancer. In vivo treatment of mice bearing lewis lung carcinoma and mammary cell carcinoma with particulate β-glucan decreased tumor weight and splenomegaly, and reduced the accumulation of polymorphonuclear-MDSC (PMN-MDSC) but not monocytic-MDSC (M-MDSC) in the spleen and tumor. In addition, particulate β-glucan differentially modulated the function of different MDSC subsets; it enhanced PMN-MDSC respiratory burst and apoptosis, and induced the differentiation of M-MDSC into …

Characterization Of Host Immune Responses To Eimeria Adenoeides Infection In Turkey Poults, Ujvala Deepthi Gadde

Graduate Theses and Dissertations

Coccidiosis is a common enteric disease of turkeys that is caused by protozoan parasites belonging to the genus Eimeria. There are about seven species of Eimeria that affect turkeys and of these E. adenoeides is the most pathogenic and commonly recognized. Infection with Eimeria is known to induce a long lasting protective immunity in chickens, but nothing is known regarding the acquisition of immunity to Eimeria in turkeys. The experiments reported here were aimed at investigating the biological and cellular immune response to E. adenoeides in turkey poults under different conditions of exposure. In experiment 1 (Chapter II), 20 …

The Genetic Complexity Of The Human Fc-Gamma Receptor 1q23 Locus And Its Relationship To Autoimmunity, Travis Samuel Ptacek

All ETDs from UAB

The human immune system must be able to adapt to a wide spectrum of invading pathogens in order to keep the human body alive. This variation includes directed recombination and mutation at the level of the individual and genetic variation and natural selection at the population level. A direct consequence of the adaptability of the immune system is autoimmunity: as the immune system adapts to a shifting spectrum of antigens, it can shift to self-antigens, and therefore attack the body and cause disease. Since genetic factors are part of this adaptability, they are also connected with autoimmune disease. SLE is …

Induction Of Stronger And Long Lasting Vaccine Immunity To Tuberculosis, Pearl Bakhru

Dissertations & Theses (Open Access)

Tuberculosis is a major cause of death due to an infection in mankind. BCG vaccine protects against childhood tuberculosis although, it fails to protect against adult tuberculosis. BCG vaccine localizes to immature phagosomes of macrophages, and avoids lysosomal fusion, which decreases peptide antigen production. Peptides are essential for macrophage-mediated priming of CD4 and CD8 T cells respectively through MHC-II and MHC-I pathways. Furthermore, BCG reduces the expression of MHC-II in macrophages of mice after infection, through Toll-like receptor-1/2 (TLR-1/2) mediated signaling. In my first aim, I hypothesized that BCG-induced reduction of MHC-II levels in macrophages can decrease CD4 T cell …

Enhancing The Immune Response Through Ikkbeta-Induced Activation Of Nf-Kappab, Emily Hopewell

USF Tampa Graduate Theses and Dissertations

Nuclear factor-κB (NF-κB) is one of the main regulators of inflammatory and immune responses. It is a family of transcription factors composed of five members: RelA, RelB, cRel, NF-κB1 (p105/p50), and NF-κB2 (p100/p52). Homo- and hetero-dimers of family members are inhibited by inhibitor of &klappaB (IκB) family members and activated by IκB kinase (IKK) family members. The IKK family is comprised of IKKα, IKKΒ, and IKKγ. The focus of my dissertation delves into the role of NF-κB activation by IKKΒ in both an immunotherapy setting and its role in T cell mediated anti-tumor immune responses.

A central focus of immunotherapy …

Crosstalk Between Gastrointestinal Epithelial Cells And Resident Microbiota Promotes Immune Homeostasis, Eric William Rogier

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

The gastrointestinal tract houses one of the most dense and diverse communities of bacteria on the planet. The mutualistic relationship between the host and commensal microbe permits the microbe an ideal environment to grow and provides the host with increased caloric intake, maturation of the adaptive immune system, and resistance against invading pathogens. To maintain a system in which both parties benefit, the epithelium has evolved numerous strategies to ensure epithelial cells respond to microbes appropriately and that potentially hazardous commensals remain distanced from the soma proper. Breakdown of these propitiating mechanisms elicits unchecked inflammation and can lead to pathology …

The Effect Of Total Work Performed During Acute Heavy Resistance Exercise On Circulating Lymphocytes In Untrained Men, Neil A. Kelly Jr

Master's Theses

Lymphocytes are one of many leukocytes which exert a biphasic response to acute intense resistance exercise. Exercise volume (i.e. total work) has been shown to have an immunomodulatory effect. This study evaluates the effect of total work performed during an intense resistance exercise protocol on lymphocyte concentrations in the circulation. Untrained, college-aged (18-35) males who performed high amounts of work (HW) were compared to those who performed low amounts of work (LW). Resistance exercise testing consisted of 6 sets of 10 repetitions of the squat exercise with 2 minutes rest between sets. Both HW and LW performed the same relative …

Defensins In Ocular Immunity, Minhao Wu

Wayne State University Dissertations

Corneal infection with P. aeruginosa results in corneal perforation in susceptible

B6, but not resistant BALB/c mice. This study explored their role mBD 1-4 in corneal

infection, and their potential synergy. Immunostaining and real-time RT-PCR data

demonstrated that their expression was either constitutive (mBD1 and mBD2) or

inducible (mBD3 and mBD4) in normal BALB/c and B6 corneas, and disparately

regulated in BALB/c vs B6 corneas after infection. Knock down studies using siRNA

treatment indicated that mBD2 and mBD3, but neither mBD1 nor mBD4, is required in

ocular defense. Moreover, in vivo studies demonstrated individual and combined effects

of mBD2 and …

The Development Of Humoral And Cellular Responses To Plasmodium Falciparum Malaria In The Hypoendemic Peruvian Amazon And Potential Clinical Protection, Eva Helen Clark

All ETDs from UAB

Each year 300-500 million cases of Plasmodium falciparum malaria occur, leading to more than 1 million deaths. In high malaria transmission regions, development of immunity from severe infection requires 2-10 years of persistent parasitemia. This delay has been attributed to difficulties in the development of protective humoral responses. Indeed, anti-malarial antibody responses tend to be short-lived, and immunologic memory seems to be dysfunctional in high-transmission regions. In contrast, in the low-transmission Peruvian Amazon >60% of infections are asymptomatic, suggesting that clinical immunity occurs despite low parasite exposure. To analyze more precisely the naturally-acquired humoral responses to malarial antigens and their …

Mechanisms Of Major Outer Membrane Protein (Momp)-Vaccine Induced Protective Immunity Against Chlamydia Muridarum Genital Infection, Christina M. Farris

All ETDs from UAB

Urogenital infection with Chlamydia trachomatis is the most common bacterial sexually transmit-ted disease with an estimated 90 million new infections occurring each year worldwide. In women infection with C. trachomatis can result in serious complications including ectopic pregnancy, pelvic inflammatory disease and tubal factor infertility. Despite very effective antimicrobial chemotherapy, control of the infection will likely require an effective vaccine. We have assessed the protective effect of an outer membrane based vaccine using a murine model of chlamydial genital tract infection. Female mice were vaccinated with C. muridarum major outer membrane protein (MOMP) plus the immunostimulatory adjuvants CpG-1826 and Montanide …