Determining The Genetic And Phenotypic Profile Of Cord Blood Derived T Regulatory Cells And The Effect Of Calcitriol On Immune Suppression, 2020 Loyola University Chicago
Determining The Genetic And Phenotypic Profile Of Cord Blood Derived T Regulatory Cells And The Effect Of Calcitriol On Immune Suppression, Anya Nikolai-Yogerst
Dissertations
Recent outbreaks in vertically transmitted viruses, such as Zika virus and HIV, have rejuvenated interest in fetal and neonatal immune tolerance. Babies are susceptible to vertically transmitted viruses because fetal and neonatal immune systems are considered to be immune-privileged and will tolerate antigens presented to them by their mother. Thus, understanding the mechanisms of this tolerance is important to design effective treatments for infected mothers to protect their offspring. Here, I define a novel Treg, a type of T cell that mediates tolerance, named bidirectional T cells (BiT), found in human umbilical cord blood (UCB). These cells are induced by …
Nlrp6 In Gram-Positive Pneumonia And Sepsis, 2019 Louisiana State University and Agricultural and Mechanical College
Nlrp6 In Gram-Positive Pneumonia And Sepsis, Laxman Ghimire
LSU Doctoral Dissertations
Acute lower respiratory infections (pneumonia) and pneumonia-derived sepsis are among the leading causes of death in the world causing 7.8 million deaths annually. In this regard, Methicillin-resistant Staphylococcus aureus (MRSA) is endemic in the US and implicated for causing high mortality-associated necrotizing pneumonia and aggravating viral pneumonia with superinfection. Additionally, sepsis is the 7th leading cause of death among newborns in the US and is responsible for more than 750,000 hospitalization cases every year. Although there is a plethora of research in both pneumonia and sepsis, the detailed pathophysiology still remains elusive. Understanding the host defense mechanism will help …
Intravital Imaging In A Zebrafish Model Elucidates Interactions Between Mucosal Immunity And Pathogenic Fungi, 2019 University of Maine
Intravital Imaging In A Zebrafish Model Elucidates Interactions Between Mucosal Immunity And Pathogenic Fungi, Linda S. Archambault
Electronic Theses and Dissertations
Candida yeasts are common commensals that can cause mucosal disease and life-threatening systemic infections. While many of the components required for defense against Candida albicans infection are well established, questions remain about how various host cells at mucosal sites assess threats and coordinate defenses to prevent normally commensal organisms from becoming pathogenic. Using two Candida species, C. albicans and C. parapsilosis, which differ in their abilities to damage epithelial tissues, we used traditional methods (pathogen CFU, host survival, and host cytokine expression) combined with high-resolution intravital imaging of transparent zebrafish larvae to illuminate host-pathogen interactions at the cellular level …
Il-17-Cxcr2 Axis Promotes Breast Cancer Metastasis And Therapy Resistance, 2019 University of Nebraska Medical Center
Il-17-Cxcr2 Axis Promotes Breast Cancer Metastasis And Therapy Resistance, Lingyun Wu
Theses & Dissertations
Cancer-related fatalities rank as the second leading cause of death in all ages and both genders in the United States. Moreover, breast cancer-related mortality rank as the second leading cause of death in females in the United States in 2019. The main concerns regarding breast cancer management include chemotherapy resistance and metastasis. Thus, the advanced understanding of cancer progression is required to develop improved therapeutic methods for breast cancer patients.
Recent studies demonstrate that neutrophils, as the most abundant leukocytes, play an essential role in breast progression. However, the mechanisms regarding neutrophils recruitment to the tumor sites, and the precise …
Natural Autoantibodies: Origin, Function And Utility For Diagnosis Of Disease, 2019 Rowan University
Natural Autoantibodies: Origin, Function And Utility For Diagnosis Of Disease, Abhirup Sarkar
Graduate School of Biomedical Sciences Theses and Dissertations
Autoantibodies (aAbs) by the simplest definitions have been described as antibodies against self-antigens and were exclusively associated with autoimmune diseases. Eventually, studies demonstrated that they are abundant in the blood of all human sera, regardless of age, gender, or the presence or absence of disease, and were thus named as ‘natural autoantibodies’. The underlying reason for their ubiquity has remained elusive, but we have hypothesized that they are responsible for clearing blood-borne cell and tissue debris generated under conditions of health and disease. To test this, we chose to use two widely different disease model systems, namely neurodegenerative diseases and …
The Distinct Expressions Of Integrins Αdβ2 And Αmβ2 Differently Regulate Macrophage Migration In 3d Matrix In Vitro And In Tissue During Inflammation, 2019 East Tennessee State University
The Distinct Expressions Of Integrins Αdβ2 And Αmβ2 Differently Regulate Macrophage Migration In 3d Matrix In Vitro And In Tissue During Inflammation, Kui Cui
Electronic Theses and Dissertations
Chronic inflammation is an essential mechanism during the development of cardiovascular and metabolic diseases. The outcome of diseases depends on the balance between the migration and accumulation of macrophages in damaged tissues. Macrophage motility is highly regulated by adhesive receptors, integrins. Namely, intermediate expression of integrin supports macrophage migration, while a high integrin density inhibits it. Our studies are focused on evaluation of the contribution of related integrins αDβ2 and αMβ2 to macrophage migration and development of chronic inflammation.
We found that integrin αDβ2 is upregulated on M1-macrophages in vitro and …
Brain-Specific And Systemic Inflammatory Response Following Repetitive Concussive Impact In A Mouse Model, 2019 The University of Western Ontario
Brain-Specific And Systemic Inflammatory Response Following Repetitive Concussive Impact In A Mouse Model, So Young Eo
Electronic Thesis and Dissertation Repository
Concussion is the most common form of mild traumatic brain injury (mTBI). TBI resolution is modulated by neuroinflammation, which is augmented by the infiltration of innate immune cells from the circulation. Peripheral, myeloid immune cells not only invade neural tissues but other organs as well causing local inflammation and tissue damage, known as systemic inflammatory response syndrome. Here, I assessed the temporal and anatomical nature of the neural and systemic cellular inflammatory response to repetitive, mTBI in a 3-hit mouse model of concussion. The results showed significant microglial activity, accumulation of peripheral myeloid cells and prominent axonal damage post-injury. The …
Iiv-6 Inhibits Nf-Kappab Responses In Drosophila, 2019 University of Massachusetts Medical School
Iiv-6 Inhibits Nf-Kappab Responses In Drosophila, Cara C. West, Florentina Rus, Ying Chen, Anni Kleino, Monique Gangloff, Don B. Gammon, Neal S. Silverman
Neal Silverman
The host immune response and virus-encoded immune evasion proteins pose constant, mutual selective pressure on each other. Virally encoded immune evasion proteins also indicate which host pathways must be inhibited to allow for viral replication. Here, we show that IIV-6 is capable of inhibiting the two Drosophila NF-kappaB signaling pathways, Imd and Toll. Antimicrobial peptide (AMP) gene induction downstream of either pathway is suppressed when cells infected with IIV-6 are also stimulated with Toll or Imd ligands. We find that cleavage of both Imd and Relish, as well as Relish nuclear translocation, three key points in Imd signal transduction, occur …
Control Of Antiviral Innate Immune Response By Protein Geranylgeranylation, 2019 Duke University
Control Of Antiviral Innate Immune Response By Protein Geranylgeranylation, Shigao Yang, Zhaozhao Jiang, Katherine A. Fitzgerald, Donghai Wang
Katherine A. Fitzgerald
The mitochondrial antiviral signaling protein (MAVS) orchestrates host antiviral innate immune response to RNA virus infection. However, how MAVS signaling is controlled to eradicate virus while preventing self-destructive inflammation remains obscure. Here, we show that protein geranylgeranylation, a posttranslational lipid modification of proteins, limits MAVS-mediated immune signaling by targeting Rho family small guanosine triphosphatase Rac1 into the mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs) at the mitochondria-ER junction. Protein geranylgeranylation and subsequent palmitoylation promote Rac1 translocation into MAMs upon viral infection. MAM-localized Rac1 limits MAVS' interaction with E3 ligase Trim31 and hence inhibits MAVS ubiquitination, aggregation, and activation. Rac1 also facilitates …
A High Throughput Assay For The Detection Of Stimulator Of Interferon Genes (Sting) Agonists, 2019 Rowan University
A High Throughput Assay For The Detection Of Stimulator Of Interferon Genes (Sting) Agonists, Michael J. Ingling
Graduate School of Biomedical Sciences Theses and Dissertations
The innate immune system includes a menagerie of different cell types, each with a different role in the process of monitoring the body for invaders and presenting gathered debris (antigen) to the adaptive immune system. Somatic cells have intracellular receptors for the same purpose. Cancer cells, however, have avoided these methods of detection despite, in many cases, the tumor’s immunogenic traits. Immuno-oncology is a field dedicated to the immunological traits of tumors, more recently finding ways of instigating an immune response against tumors. In this regard, STING, a receptor of cyclic dinucleotides (CDN), has come to the forefront of immuno-oncology. …
Development Of A Prolyl Endopeptidase Expression System In Lactobacillus Reuteri To Reduce The Clinical Manifestation Of Celiac Disease, 2019 California Polytechnic State University, San Luis Obispo
Development Of A Prolyl Endopeptidase Expression System In Lactobacillus Reuteri To Reduce The Clinical Manifestation Of Celiac Disease, Kara Lynn Jew
Master's Theses
Celiac Disease (CD) is an autoimmune disorder that emerges due to the ingestion of gluten, a protein found in a variety of common grains such as wheat, rye, and barley. Approximately 1 in 100 individuals in the US suffer from CD, making it the most commonly diagnosed gastrointestinal disorder (Ciclitira et. al., 2005). These proline-rich gluten peptides are resistant to proteolysis and accumulate in the duodenum of the small intestine. Once in the duodenum, these peptides illicit an autoimmune response resulting in villous atrophy. Current treatment for CD requires a rigorous adherence to a gluten-free diet. Nevertheless, gluten-containing grains are …
The Wet Bridge Transfer System: An Novel In Vitro Tool For Assessing Exogenous Surfactant As A Pulmonary Drug Delivery Vehicle, 2019 University of Western Ontario
The Wet Bridge Transfer System: An Novel In Vitro Tool For Assessing Exogenous Surfactant As A Pulmonary Drug Delivery Vehicle, Brandon J. Baer
Western Research Forum
Background:
Due to its complex branching structure, direct drug delivery to the remote areas of the lung is a major challenge. Consequently, most therapies, such as those treating pulmonary infection and inflammation, must utilize large systemic dosing, with the potential for adverse side effects. A novel alternative strategy is to use exogenous surfactant, a material capable of distributing throughout the lung, as a pulmonary drug delivery vehicle.
Objective:
Utilize an in vitro transferring system to assess exogenous surfactant (BLES) as a pulmonary delivery vehicle for different therapeutics.
Methods:
An in vitro technique was developed to simultaneously study surfactant delivery and …
Understanding The Role Of Macrophages In Lung Inflammation Through Mathematical Modeling, 2019 Virginia Commonwealth University
Understanding The Role Of Macrophages In Lung Inflammation Through Mathematical Modeling, Sarah B. Minucci
Biology and Medicine Through Mathematics Conference
No abstract provided.
The Cxcr2-Dependent Role Of Cancer-Associated Fibroblasts In Pancreatic Ductal Adenocarcinoma, 2019 University of Nebraska Medical Center
The Cxcr2-Dependent Role Of Cancer-Associated Fibroblasts In Pancreatic Ductal Adenocarcinoma, Mohammad Awaji
Theses & Dissertations
Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer, the fourth leading cause of cancer-related deaths in the USA with over 40,000 deaths per year. Unlike other major cancer types, the progress in dealing with PDAC is plodding, attributed mainly to the asymptomatic nature of the disease, the late diagnosis and the ineffectiveness of current therapies. A better understanding of the biology of the disease could permit the discovery of novel diagnostic and therapeutic tools. With that in mind, we present this dissertation that investigates the tumor-stromal interaction underlined by genetic alterations and inflammation. PDAC develop as …
Constitutive Interferon Signaling Maintains Critical Threshold Of Mlkl Expression To License Necroptosis, 2019 Tufts University
Constitutive Interferon Signaling Maintains Critical Threshold Of Mlkl Expression To License Necroptosis, Joseph Sarhan, Beiyun C. Liu, Hayley I. Muendlein, Chi G. Weindel, Irina Smirnova, Amy Y. Tang, Vladimir Ilyukha, Maxim Sorokin, Anton Buzdin, Katherine A. Fitzgerald, Alexander Poltorak
Katherine A. Fitzgerald
Interferons (IFNs) are critical determinants in immune-competence and autoimmunity, and are endogenously regulated by a low-level constitutive feedback loop. However, little is known about the functions and origins of constitutive IFN. Recently, lipopolysaccharide (LPS)-induced IFN was implicated as a driver of necroptosis, a necrotic form of cell death downstream of receptor-interacting protein (RIP) kinase activation and executed by mixed lineage kinase like-domain (MLKL) protein. We found that the pre-established IFN status of the cell, instead of LPS-induced IFN, is critical for the early initiation of necroptosis in macrophages. This pre-established IFN signature stems from cytosolic DNA sensing via cGAS/STING, and …
Abrogation Of Endogenous Glycolipid Antigen Presentation On Myelin-Laden Macrophages By D-Sphingosine Ameliorates The Pathogenesis Of Experimental Autoimmune Encephalomyelitis, 2019 Weill Cornell Medical College
Abrogation Of Endogenous Glycolipid Antigen Presentation On Myelin-Laden Macrophages By D-Sphingosine Ameliorates The Pathogenesis Of Experimental Autoimmune Encephalomyelitis, Yi Ban, Wenjuan Dong, Lixing Zhang, Tian Zhou, Ahmad Sabri Altiti, Khaleel Ali, David R. Mootoo, Victoria A. Biaho, Timothy Hla, Yi Ren, Xiaojing Ma
Publications and Research
Background: Although myelin is composed of mostly lipids, the pathological role of myelin lipids in demyelinating diseases remains elusive. The principal lipid of the myelin sheath is b-galactosylceramide (b-Galcer). Its a-anomer (a-Galcer) has been demonstrated to be antigenically presented by macrophages via CD1d, a MHC class I-like molecule. Myelin, which is mostly composed of b-Galcer, has been long considered as an immunologically-inert neuron insulator, because the antigen-binding cleft of CD1d is highly a-form-restricted.
Results: Here, we report that CD1d-mediated antigenic presentation of myelin-derived galactosylceramide (Mye-GalCer) by macrophages contributed significantly to the progression of experimental autoimmune encephalomyelitis (EAE). Surprisingly, this presentation …
Pyocyanin, A Virulence Factor Produced By Sepsis-Causing Pseudomonas Aeruginosa, Promotes Adipose Wasting And Cachexia, 2019 University of Kentucky
Pyocyanin, A Virulence Factor Produced By Sepsis-Causing Pseudomonas Aeruginosa, Promotes Adipose Wasting And Cachexia, Nika Larian
Theses and Dissertations--Pharmacology and Nutritional Sciences
Sepsis is a leading cause of death among critically ill patients that results in metabolic alterations including hypercatabolism, lipoatrophy, and muscle wasting, contributing to the development of cachexia. Septic cachexia is associated with loss of body weight, fat mass, and lean mass and dysregulated immune function. There are currently no efficacious treatment strategies for septic cachexia, and nutritional interventions have limited success in preventing hypercatabolic wasting. Pyocyanin is a virulence factor produced by sepsis-causing Pseudomonas aeruginosa that has been shown to activate the aryl hydrocarbon receptor (AhR), increase inflammation, and produce reactive oxygen species. Thus, pyocyanin represents a novel mechanistic …
The Effects Of Heat-Killed Echinostomatid Parasites On Mice Treated With Dextran Sodium Sulfate (Dss), 2019 Minnesota State University, Mankato
The Effects Of Heat-Killed Echinostomatid Parasites On Mice Treated With Dextran Sodium Sulfate (Dss), Natalie Gooder
All Graduate Theses, Dissertations, and Other Capstone Projects
Objective: Autoimmune diseases are chronic, incurable, and affect approximately 50 million Americans. This is a strong need for better ways to treat autoimmune diseases. Parasites and parasite proteins have been observed to protect mice from symptoms of induced colitis in mice treated with dextran sodium sulfate (DSS), a model for inflammatory bowel disease (IBD). I hypothesize that non-living echinostomatid parasites, given during DSS treatment, can decrease intestinal inflammation and weight loss, providing a possible novel treatment for IBD.
Methods: A range of DSS concentrations (0.5%-3%) were delivered to female C57BL/6 mice in their drinking water in order to determine the …
Antibodies In The Diagnosis, Prognosis, And Prediction Of Psychotic Disorders., 2019 King's College London
Antibodies In The Diagnosis, Prognosis, And Prediction Of Psychotic Disorders., Thomas A Pollak, Jonathan P Rogers, Robert G Nagele, Mark Peakman, James M Stone, Anthony S David, Philip Mcguire
Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship
Blood-based biomarker discovery for psychotic disorders has yet to impact upon routine clinical practice. In physical disorders antibodies have established roles as diagnostic, prognostic and predictive (theranostic) biomarkers, particularly in disorders thought to have a substantial autoimmune or infective aetiology. Two approaches to antibody biomarker identification are distinguished: a "top-down" approach, in which antibodies to specific antigens are sought based on the known function of the antigen and its putative role in the disorder, and emerging "bottom-up" or "omics" approaches that are agnostic as to the significance of any one antigen, using high-throughput arrays to identify distinctive components of the …
Evaluating The Effects Of Antibody-Conjugated Multi-Walled Carbon Nanotubes In Combination With Microwave Irradiation, 2019 Georgia Southern University
Evaluating The Effects Of Antibody-Conjugated Multi-Walled Carbon Nanotubes In Combination With Microwave Irradiation, Amy Chall
Electronic Theses and Dissertations
Cancer remains one of the largest public health concerns of our day, particularly in developed countries where technological advances have allowed populations to live well into their eighth decade. In America, those in their 80’s have a 1 in 2 chance of developing cancer in their lifetime. Prostate cancer, specifically is the second leading cause of cancer deaths in males. Traditional cancer therapies cause high levels of toxicity to the patient due to mechanisms of action that often attack cancer cells and healthy cells alike. The holy grail of cancer research is to find a treatment that targets the cancer …