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Full-Text Articles in Life Sciences

The Characterization Of Inflammatory Extracellular Vesicles, Barak Balva Jan 2020

The Characterization Of Inflammatory Extracellular Vesicles, Barak Balva

Master's Theses

One of the driving factors behind innate immunity is the early response of inflammation. While beneficial in controlling infections, when uncontrolled it can lead to a plethora of disorders. Thus, it is essential to understand the driving factors behind inflammation. a cell's ability to recycle, discard, or transfer proteins is integral for survival and intercellular communication. It has been appreciated that inflammatory components, such as caspase-1, play a huge role in driving protein secretion. Thus, inflammation also plays a role in the distribution of proteins released from cells. These proteins are released via non-conventional secretory pathways, and our lab is …


Characterization Of Caspase 1 Substrate Specificity Utilizing Luminescent Reporter Constructs, Nicholas Rohlfes Jan 2020

Characterization Of Caspase 1 Substrate Specificity Utilizing Luminescent Reporter Constructs, Nicholas Rohlfes

Master's Theses

Inflammation is the bodies first response to defend itself against foreign pathogens and damage. Cellular sensors are constantly monitoring the body and checking for homeostatic disruption. Microbial pathogens and tissue damage are sensed by pattern recognition receptors (PRRs), which sense pathogen associated molecular patterns and damage associated molecular patterns, termed PAMPs and DAMPs respectively. Within the family of PRRs are sensors that can induce the formation of the multi-protein complex termed the inflammasome following activation. the inflammasome complex is a molecular platform for which caspase 1, a cysteine protease, is incorporated and is responsible for the maturation of pro-inflammatory cytokines …


Suffocated Cd8 T Cells In The Hypoxic Tumor Microenvironment, Lourdes Beatriz Plaza Rojas Jan 2020

Suffocated Cd8 T Cells In The Hypoxic Tumor Microenvironment, Lourdes Beatriz Plaza Rojas

Dissertations

Hypoxia is a common feature of solid tumors that plays an important role in angiogenesis, malignant progression and metastatic development. However, its impact on T cell anti-tumor responses is less known. We determined that CD8 tumor infiltrating lymphocytes (TILs) tend to localize to non-hypoxic tumor areas, suggesting a susceptibility to tumor-associated hypoxia. This led us to further study the effects of hypoxia in vitro by culturing spleen-derived mouse T cells in a humidified chamber at 0.5% O2, 5% CO2 and 37 °C. We found that T cell proliferation and effector function are reduced by hypoxia, severely affecting inflammatory cytokine production. …


Determining The Genetic And Phenotypic Profile Of Cord Blood Derived T Regulatory Cells And The Effect Of Calcitriol On Immune Suppression, Anya Nikolai-Yogerst Jan 2020

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 …


Induction Of Zika And Dengue Virus-Specific Cd8+ T Cells By Means Of Dna Vaccine, Natalie Jachym Jan 2020

Induction Of Zika And Dengue Virus-Specific Cd8+ T Cells By Means Of Dna Vaccine, Natalie Jachym

Master's Theses

Zika virus (ZIKV) and Dengue virus (DENV) are flaviviruses that circulate in the same endemic regions and can co-infect the same individual. While primary infection by DENV leads to life-long immunity to the infecting serotype, it does not provide immunity to other serotypes. Moreover, ZIKV and DENV antibodies can be cross-reactive and potentially enhance infection of the other virus through a process known as antibody-dependent enhancement (ADE). In this mechanism, antibodies weakly bind the infecting virus and direct virions to immunoglobulin Fc receptors on macrophages. This promotes viral uptake and infection rather than neutralize the virus. Due to this mechanism, …


Enabling The Clinical Detection Of Human Papilloma Virus (Hpv) To Enhance Effective Diagnosis And Research, Jennifer Sackey Jan 2020

Enabling The Clinical Detection Of Human Papilloma Virus (Hpv) To Enhance Effective Diagnosis And Research, Jennifer Sackey

Master's Theses

Human Papilloma Virus (HPV) is one of the most common sexually transmitted infections. There are over 150 different genotypes of HPV. Some cause benign warts, while others cause several types of cancer. Subunit vaccines comprised of the capsid protein from an increasing number of HPV genotypes have been developed; however, the vaccines are prophylactic and are documented to protect against only 9 of the HPV genotypes. Importantly, there are also significant limitations in the clinical detection of HPV. Current clinical tests can only specifically identify HPV16 and HPV18. One of the test also detects 12 of the other high-oncogenic risk …


Transforming Growth Factor Beta Suppression Of Cd8+ T Cell Proliferation, Shena Geisinger Jan 2020

Transforming Growth Factor Beta Suppression Of Cd8+ T Cell Proliferation, Shena Geisinger

Master's Theses

Transforming Growth Factor Beta (TGF-beta) is highly suppressive to both CD4+ and CD8+ T cell proliferation and function. in tumor microenvironments, TGF-beta has been described as immune suppressive, particularly to CD8+ T cells, however, the molecular mechanism behind how TGF-beta signaling controls T cell growth is not fully understood. Here, we report that TGF-beta inhibits CD8+ T cell proliferation and reduces expression of the CARMA1/BCL10/MALT1 (CBM) signalosome complex in activated CD8+ T cells. the CBM signalosome is an essential scaffold that forms after T cell receptor (TCR) stimulation, leading to the activation of NF-kB and AP-1. This observed reduction in …


Developing Caspase-1 Biosensors To Monitor Inflammation In Vitro And In Vivo, Sarah Talley Jan 2020

Developing Caspase-1 Biosensors To Monitor Inflammation In Vitro And In Vivo, Sarah Talley

Dissertations

Inflammation is central to the pathogenesis of numerous human diseases. in many contexts, inflammation drives immune responses which are critical to protection against many pathogens. However, uncontrolled inflammation can drive the pathology of numerous diseases, including neurodegenerative diseases, intestinal disorders, cancer, and autoimmune diseases. a primary mediator of inflammation is the inflammasome complex, which drives the release of inflammatory mediators through caspase-1 activation. Our goal was to develop a tool that would allow us to monitor caspase-1 activation in vitro and ultimately in vivo. to this end, we employed a circularly permuted form of luciferase in which the N- and …