Immunity Commons^™

Elucidating The Roles Of Il-15 In The Tumor Microenvironment, Rosa Maria Santana Carrero

Dissertations and Theses (Open Access)

ELUCIDATING THE ROLES OF IL-15 IN THE TUMOR MICROENVIRONMENT

Rosa M. Santana Carrero, B.S.

Advisory Professors: Shao-Cong Sun, Ph.D. & Kimberly S. Schluns, Ph.D.

Interleukin-15 (IL-15) is a factor that promotes activation, proliferation, cytotoxicity, and survival of CD8 T cells and NK cells, and has been shown to have anti-tumor effects. Moreover, loss of IL-15 expression in human colorectal tumors correlates with increased risk of relapse, diminished survival, decreased density and proliferation of T cells. All together these findings suggest that IL-15 expressed locally in the tumor microenvironment (TME) is an important mediator of anti-tumor responses by tumor infiltrating lymphocytes …

Micrornas Associated With Melanoma Inflammation And Response To Pd-1 Inhibition, Robert Szczepaniak Sloane

Dissertations and Theses (Open Access)

Melanoma is an aggressive malignancy of melanocytes with historically poor outcomes. Melanoma therapy has improved markedly over the past decade with advances in molecularly targeted agents and immunotherapies. Immune checkpoint inhibitors achieve T-cell mediated anti-tumor efficacy by blocking engagement of inhibitory checkpoints on T-cells to overcome immunosuppressive signals from tumor cells and the broader microenvironment. Despite these advances, there are a significant proportion of patients who do not benefit from existing immunotherapy strategies making it a priority to identify and target the mechanisms that confer resistance to therapy. We demonstrate that microRNAs are accurate markers of microenvironment composition with prognostic …

Fibroblast Heterogeneity In Pancreatic Cancer Immunity, Josephine Darpolor

Dissertations and Theses (Open Access)

Fibroblasts are a unique cell type defined by their mesenchymal phenotype and exclusion from epithelial, immune, and endothelial cell subsets. Although well studied in wound healing, cancer associated fibroblasts (CAFs) are incredibly heterogeneous, leading to contradictions as to the roles CAFs play in the tumor microenvironment (TME). CAFs were thought to be a barrier to treatment of pancreatic ductal adenocarcinoma (PDAC). However, general stromal targeting strategies have largely failed in the clinic likely due to the heterogeneity of CAFs in the TME. Therefore, our groups and others have worked to unravel the heterogeneity of CAFs in PDAC. In the works …

Applying Immuno-Epidemiology Principles To Violence, Anna H. Sisk, Nina H. Fefferman, Judy Day, Patricia Bamwine

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Mucosal Immune System Of African Lungfish, Ryan D. Heimroth

Biology ETDs

Conquering land was an apex moment in the evolution of vertebrates. Physiologically, the first vertebrates to transition to life on land had to adapt in order to survive in an oxygen-rich environment where gravitational forces and limited water prevailed. Several extant vertebrates including anurans and lungfish, survive droughts by undergoing aestivation. Unfavorable environmental conditions trigger lungfish to aestivate. Aestivation is a process of metabolic torpor wherein the fish will encase itself in a mucus cocoon and not move until favorable environmental conditions (food and water) are reintroduced. Aestivation can be reproduced in laboratory settings and, thus, lungfish can be used …

Neutrophil-To-Lymphocyte Ratio: A Biomarker To Monitor The Immune Status Of Astronauts, Amber M. Paul, Siddhita D. Mhatre, Egle Cekanaviciute, Ann-Sofie Schreurs, Candice G.T. Tahimic, Ruth K. Globus, Sulekha Anand, Brian E. Crucian, Sharmila Bhattacharya

Publications

A comprehensive understanding of spaceflight factors involved in immune dysfunction and the evaluation of biomarkers to assess in-flight astronaut health are essential goals for NASA. An elevated neutrophil-to-lymphocyte ratio (NLR) is a potential biomarker candidate, as leukocyte differentials are altered during spaceflight. In the reduced gravity environment of space, rodents and astronauts displayed elevated NLR and granulocyte-to-lymphocyte ratios (GLR), respectively. To simulate microgravity using two well-established ground-based models, we cultured human whole blood-leukocytes in high-aspect rotating wall vessels (HARV-RWV) and used hindlimb unloaded (HU) mice. Both HARV-RWV simulation of leukocytes and HU-exposed mice showed elevated NLR profiles comparable to spaceflight …

Genomic And Transcriptomic Alterations In Metabolic Regulators And Implications For Anti-Tumoral Immune Response, Ryan J. King

Theses & Dissertations

Metabolic and immune alterations are ubiquitous hallmarks of cancer that are established during the foundational mutations and are further selected upon to generate highly aggressive tumors. Recent evidence suggests that cancer cells employ an altered metabolism to induce immune evasion. To further discover the relationship between metabolism and immunity in cancer, this thesis aimed to discover potential candidates of interest by first examining the mucin family for differences, as they exert a wide range of activities in cancer, including altered metabolism and immune alterations. Unique differences lead to further profiling in pancreatic and esophageal cancer. In pancreatic cancer, CD73 was …

Development, Expansion And Role Of Myeloid-Derived Suppressor Cells In Post-Sepsis Immune Suppression, Tuqa Alkhateeb

Electronic Theses and Dissertations

Myeloid-derived suppressor cells (MDSCs) numbers increase significantly in sepsis and are associated with high mortality rates. These myeloid cell precursors promote immunosuppression, especially in the late (post sepsis) stage. However, the mechanisms that underlie MDSC expansion and programming are not completely understood. To investigate these mechanisms, we used a cecal-ligation and puncture (CLP) mouse model of polymicrobial sepsis that progresses from an early/acute proinflammatory phase to a late/chronic immunosuppressive phase. Previous studies in our laboratory showed that microRNA (miR)-21 and miR-181b elevate levels of the transcription factor nuclear factor 1 (NFI-A) that promotes MDSC expansion. We report here that miR-21 …

Investigating The Role Of Quaking In Antigen Uptake And Cross-Presentation By Dendritic Cells, Yating Li

Dissertations and Theses (Open Access)

Dendritic cells (DCs) are considered the most potent antigen presenting cells (APC) due to their superior capability of cross-presenting exogenous antigens to CD8⁺ T cell for strong adaptive immune responses. They internalize foreign antigens by phagocytosis, endocytosis or macropinocytosis, which are then processed in endosomal compartments and loaded onto MHC Class I molecules. However, the molecular mechanisms regulating exogenous antigen uptake and cross-presentation by DCs are not fully understood.

In this study, we discovered that an RNA-binding protein, Quaking (QKI) plays a pivotal role in antigen uptake by DCs. Our previous studies in neural stem cells and microglia have …

Quercetin And Vitamin C: An Experimental, Synergistic Therapy For The Prevention And Treatment Of Sars-Cov-2 Related Disease (Covid-19), Ruben Manuel Luciano Colunga Biancatelli, Max Berrill, John D. Catravas, Paul Ellis Marik

Bioelectrics Publications

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) represents an emergent global threat which is straining worldwide healthcare capacity. As of May 27th, the disease caused by SARS-CoV-2 (COVID-19) has resulted in more than 340,000 deaths worldwide, with 100,000 deaths in the US alone. It is imperative to study and develop pharmacological treatments suitable for the prevention and treatment of COVID-19. Ascorbic acid is a crucial vitamin necessary for the correct functioning of the immune system. It plays a role in stress response and has shown promising results when administered to the critically ill. Quercetin is a well-known flavonoid whose antiviral properties …

Modulating Matrix Metalloproteases And Inflammation In Huntington’S Disease, Alejandro Lopez Ramirez

Natural Sciences and Mathematics | Biological Sciences Master's Theses

Huntington’s disease (HD) is a rare and incurable autosomal neurodegenerative disease affecting 1-10 in every 100,000 people in the world. There is no cure for HD and treatments available alleviate certain symptoms for short periods of time. Evidence suggests that neuropathology of HD begins with the proteolysis of the mutated Huntingtin (mHTT) protein. A variety of proteases, like the matrix metalloproteases, cleave mHTT creating proteinaceous fragments that are thought to be neurotoxic. As these fragments increase in the brain, the damage to neurons also increases, leading to chronic inflammation due to hyper reactive microglia and astrocytes attempting to minimize and …

Modeling Vaccination Strategies To Control White-Nose Syndrome In Little Brown Bat Colonies, Eva Cornwell, David Elzinga, Shelby R. Stowe, Alex Capaldi

Biology and Medicine Through Mathematics Conference

No abstract provided.

In Silico Mouse Model Of Infection And Immunity, Daniel Jonas, Michael Kirby, Alan R. Schenkel

Biology and Medicine Through Mathematics Conference

No abstract provided.

The Critical Role Of Tnf Receptors Versus Nadph Oxidase In Controlling Babesia Microti Infection, Amal Balahmar

NYMC Student Theses and Dissertations

Babesia microti is an apicomplexan parasite transmitted by tick bite that infects red blood cells. It is increasingly associated with transfusion-transmitted infections including fatal infection as the parasite survives blood banking procedures. The infection can range from asymptomatic to fatal. The parasite can persist in relatively asymptomatic individuals for up to two years. The host and parasite determinants of severity of infection and/or parasite clearance remain largely unknown. However, asplenic and immune suppressed individuals including the very young and relatively old, greater than 50 years of age, are more vulnerable to severe disease. The goal of the current research is …

The Relationship Between Glucocorticoids And The Humoral Immune Response To Mycoplasma Gallisepticum Challenges In Eastern Bluebirds, Joshua Smith

Honors Theses

Numerous studies have examined relationships between adrenal glucocorticoids and the immune system’s ability to fight disease. The relationship can vary, with glucocorticoids having either stimulatory or inhibitory effects. The pathogenic bacterium Mycoplasma gallisepticum (MG) elicits an adaptive immune response in birds, in which B cells produce MG-specific antibodies to fight the infection and prevent reoccurrence. Previous research found that Eastern Bluebirds that produce the most antibodies in response to MG infection also have the highest glucocorticoid levels. This finding led to the current study investigating whether corticosterone, the primary glucocorticoid in birds, stimulates production of antibodies in response to immune …

Development Of An Attenuated Zika Virus By Editing The 5’ Untranslated Region, E. Ashley Thompson

Master's Theses

Zika Virus (ZIKV) is a mosquito-transmitted flavivirus that usually causes no symptoms to mild febrile in humans, and it has been regarded as an insignificant pathogen to public health. However, recent outbreaks of ZIKV infection have revealed that ZIKV can cause severe neurological effects in adults, such as Guillain-Barre Syndrome (GBS), and in infants whose mothers acquired the virus during pregnancy, causing Congenital Zika Syndrome (CZS). Currently, no approved vaccine is available and there is a critical need to develop an effective and safe vaccine. While most vaccine developmental strategies target the viral prM-E protein of ZIKV, we aimed to …

The Autoimmune System: The Effect Of Physiological Stressors On Autoantibody Glycosylation And Fidelity Of Autoantibody Profiles, Rahil Kheirkhah

Graduate School of Biomedical Sciences Theses and Dissertations

The presence of thousands of autoantibodies (aABs) in the human sera is typical, and therefore it is possible to identify an aAB profile for each individual. In the first part of this thesis, we will show the cerebrospinal fluid also exhibits an extraordinarily complex immunoglobulin G aAB profile that is composed of thousands of aABs. We show that the pattern of expression of individual aABs in CSF closely mimics that in the blood, indicative of a blood-based origin for CSF aABs. In addition, using longitudinal serum samples obtained over a span of nine years, we show remarkable stability in aAB …

How Nutrition Can Help To Fight Against Covid-19 Pandemic, Faseeha Aman, Sadia Masood

Section of Internal Medicine

Currently Covid-19 pandemic is a leading challenge across the globe. It is mandatory to attain and maintain good nutritional status to fight against virus. Nutritional status of individual is affected by several factors such as age, sex, health status, life style and medications. Nutritional status of individuals has been used as resilience towards destabilization during this COVID-19 pandemic. Optimal nutrition and dietary nutrient intake impact the immune system, therefore the only sustainable way to survive in current context is to strengthen the immune system. There is no evidence found that supplement can cure the immune system except Vit C, which …

Exosomal Communication By Metastatic Osteosarcoma Cells Modulates Alveolar Macrophages To An M2 Tumor-Promoting Phenotype And Inhibits Tumoricidal Functions, Kerri Wolf

Dissertations and Theses (Open Access)

Osteosarcoma metastasizes to the lung, and there is a link between the predominance of tumor promoting immunosuppressive M2 macrophages in the metastases and poor patient survival. By contrast, M1macrophage predominance correlates with longer survival. M2 macrophages can be induced by various stimuli in the tumor microenvironment, including exosomes, which are 40- to 150-nm vesicles that are involved in intercellular communication and contribute to tumor progression and immune evasion. Recognizing that tumor cells can influence the tumor microenvironment to make it more permissive and because of the link between M2 dominance and curtailed patient survival, we evaluated the effect of …

Loss Of Caspase-8 Function In Combination With Smac Mimetic Treatment Sensitizes Head And Neck Squamous Carcinoma To Radiation Through Induction Of Necroptosis., Burak Uzunparmak

Dissertations and Theses (Open Access)

Caspase-8 (CASP8) is one of the most frequently mutated genes in Head and Neck Squamous Carcinomas (HNSCC), and mutations of CASP8 are associated with poor overall survival. The distribution of these mutations in HNSCC suggests that they are likely to be inactivating. Inhibition of CASP8 has been reported to sensitize cancer cells to necroptosis, a unique cell death mechanism. Here, we evaluated how CASP8 regulates necroptosis in HSNCC using cell line models and syngeneic mouse xenografts. In vitro, knockdown of CASP8 rendered HNSCCs susceptible to necroptosis induced by a second mitochondria-derived activator of caspase (SMAC) mimetic, Birinapant, when combined …

Effects Of Individual Orsay Virus Proteins On The Intracellular Pathogen Response Of C. Elegans, Barbara Chen, Jessica N. Sowa

Biology Student Work

In order to cause infection, pathogens must avoid destruction by the host immune system. However, how pathogens evolved to evade host immunity is not fully understood. Mammals have two systems of immunity, innate and adaptive, which are regulated by complex interactions between the two systems. In order to study innate immunity exclusively, the roundworm C. elegans is a useful invertebrate model because it lacks adaptive immunity and the complexities that arise from interactions between the two types of immunity. The goal of this project is to investigate whether the individual expression of the Orsay virus capsid and delta-fusion proteins can …

Identifying Novel Triggers Of The Intracellular Pathogen Response (Ipr) In C. Elegans, Catherine T. Byrnes, Jessica N. Sowa

Biology Student Work

The intracellular pathogen response (IPR) is a cell signaling pathway found in C. elegans that is triggered when pathogenic microorganisms invade, and immune responses attempt to eliminate the threat. Due to the relative simplicity of C. elegans, they are an excellent model organism to analyze the cell signaling pathways triggered by various pathogens. They lack the complex immune systems of larger organisms, making it easier to study the involved cell signaling pathways. Past studies have shown that the IPR can also be triggered via intestinal wounding. Heat stress, viral infection, and proteasome stress are all known triggers of the IPR. …

Immunotherapy: Therapy Vs. Enhancement, Mariah Daly

Honors Program Theses

The battle against cancer is a long-standing struggle that has resulted in new information and the development of novel medical technologies. Current research aims to figure out a way to reprogram cells and bodily mechanisms to eliminate those cells that are cancerous without destroying healthy cells in the process. Methods which use the body’s own mechanisms, such as immunotherapy, have shown and continue to show potential for specifically targeting cancer cells. Adoptive T cell therapy is one form of immunotherapy that has gained significant attention and focus in the field. Therapies improve conditions up to the normal state of being, …

Haemonchus Contortus Antigen Identification And Use Of Tropomyosin In Ovine Vaccine Development, Brynnan P. Russ

Graduate Theses, Dissertations, and Problem Reports (ETD)

Globally, the small ruminant industry loses hundreds of millions of dollars due to parasitism by the gastrointestinal nematode Haemonchus contortus. This parasite feeds on blood in the host’s abomasum leading to disease including anemia, hypoproteinemia, lethargy, and death. There have been exhaustive efforts to manage this parasite including different management applications, anthelmintic treatment, and now integration of resistance genetics into a flock. Like antibiotics, overuse of anthelmintics has led to resistance of H. contortus to these drugs. Therefore, other methods of control are the main focuses of many research initiatives. St. Croix are a resistant breed of sheep that mount …

Augmenting Guadecitabine To Promote Anticancer Immunity In Murine Breast Cancer, Timothy M. Smith Jr.

Theses and Dissertations

In immune-competent individuals, tumor growth occurs due to a failure of the immune system to recognize and destroy malignant cells. Immune surveillance can be curtailed by the presence of immunosuppressive cells such as myeloid-derived suppressor cells (MDSCs) and T-regulatory cells (Tregs) which both serve to dampen antitumor immunity. These studies utilize a metronomic low-dose therapeutic approach to examine the effects of anticancer drugs against murine breast cancer and the effects on the immune cell compartments. The focus of these studies revolve around the drug guadecitabine (guad), a second-generation DNA methyl-transferase inhibitor (DNMTi). DNMTi’s have been shown to dysregulate the methylation …

Using Phytoglycogen-Based Nanoparticles To Enhance Inosine Monophsophate Delivery Using Rainbow Trout And Bovine Models, Kristof Jenik

Theses and Dissertations (Comprehensive)

Recently, there has been interest in the use of nucleotides in industrials feeds, with inosine monophosphate showing the most promising effects on growth and immunity. Rainbow trout and Alberta cattle are two of Canadas most profitable farmed animals, if their growth rates and immunity could be enhanced this would further improve their value. The impacts of IMP, a phytoglycogen-based nanoparticle (NP) and inosine monophosphate cationically bound to the phytoglycogen-based nanoparticle (IMP-NP) were characterized in rainbow trout in vivo and in vitro and in vitro in bovine cells. Rainbow trout that were fed an IMP-NP containing feed on average had higher …

Pulmonary Immune Responses To Respirable Elongate Mineral Particles Of Asbestiform And Non-Asbestiform Morphologies, Timur Khaliullin

Graduate Theses, Dissertations, and Problem Reports (ETD)

Inhalation exposure to asbestiform elongate mineral particles (EMPs) may cause pulmonary fibrosis, lung and pleural cancer. At the same time, epidemiological evidence for non-asbestiform EMP pathogenicity is scarce, with little if any risk of cancer, but consistent findings of pneumoconiosis and increased mortality. Globally, conditions caused by asbestos exposures contribute most to the occupational cancer burden and are responsible for the increasing mortality for occupational respiratory diseases. Immunological components of the fiber-induced lesions are extremely understudied, partly due to the lack of comparable test articles. In this study I utilized respirable preparations of asbestiform and non-asbestiform riebeckite and tremolite to …

Assessment Of The Immune Response To Posthodiplostomum Minimum Infection In Bluegills, Olamide S. Olayinka

Masters Theses

Bluegills (Lepomis macrochirus) are common intermediate hosts for white grub (Posthodiplostomum minimum). They tolerate heavy infections with minimal effect on condition and continue to accumulate metacercariae as they age. This suggests that any immune response to this parasite might not be effective. This study was conducted to better understand the immune mechanisms underlying P. minimum infection in bluegills.

Infected organs (liver, kidney, and heart) were examined histologically, and serum from infected fish was tested for antibodies to white grub. Juvenile flukes were recovered from isolated metacercarial cysts. Polyclonal antibodies were produced in mice against white grub …

Investigation Of Rna Interference (Rnai)-Mediated Gene Silencing In Rainbow Trout, Sarah Au

Theses and Dissertations (Comprehensive)

RNA interference (RNAi) was first characterized in plants and invertebrates as an antiviral innate immune response. It is a natural antiviral defence mechanism to degrade viral RNA by virus-induced gene silencing. Studies showed synthetic long double-stranded RNA (dsRNA; >30bp) degraded Caenorhabditis elegans messenger RNA (mRNA) transcripts, resulting in sequence-dependent gene silencing. Currently, there is only limited research on RNAi in fish, particularly the use of long dsRNA to trigger sequence-specific gene silencing. This is because studies have shown long dsRNAs trigger interferon response that could mask gene-specific RNAi effects. This thesis explored long dsRNA-mediated RNAi pathways in rainbow trout cells …

Basigin As An Immune Mediator In The Cns, Alicia Gonzalez

UNF Graduate Theses and Dissertations

Chronic inflammation is a hallmark of many neurodegenerative disorders. Although the central nervous system (CNS) can stave peripheral pathogens from crossing the blood-brain barrier (BBB) through a network of continuous endothelia, astrocytes, and pericytes, prolonged exposure to a pathogen can comprise this barrier. Basigin, a cell adhesion molecule, is found on the surface of endothelial cells and has been demonstrated to interact with toll-like receptor 4 (TLR4). TLR4 recognizes lipopolysaccharide (LPS), found on the outer membrane of Gram-negative bacteria. The activation of TLR4 produces pro-inflammatory cytokines, like IL-6. The present study aims to address the expression pattern of Basigin gene …