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Disentangling Glial Diversity In Peripheral Nerves At Single Nuclei Resolution, Aldrin Kay Yuen Yim

Arts & Sciences Electronic Theses and Dissertations

The ability to discern gene expression at single cell level is revolutionizing our understanding of both basic biology and human health. Peripheral nerves are essential communicators between the outside world and the CNS, as evidenced by the devastating effects of diseases that disrupt them, such as ALS, Charcot-Marie-Tooth Syndrome and diabetic neuropathy. Understanding peripheral nerve dysfunction at a mechanistic level is of considerable interest due to the increasing prevalence and associated patient care costs of these disorders. Although most research of the peripheral nerve has focused on glial-axonal interactions, the important contributions of other cell types besides Schwann cells, such …

The Immunoregulation Of Autoimmune Diabetes, Hao Hu

Arts & Sciences Electronic Theses and Dissertations

How autoimmune diseases are regulated is a long-term research topic in the autoimmunity field. We use autoimmune diabetes as a model to study this. Autoimmune diabetes is a T cell-dependent autoimmune syndrome. The functions of T cells are regulated during their development and activation. Developmentally, T cells will undergo a stringent thymic selection: a process that self-reactive T cells are tolerized to become thymic derived Tregs or can be deleted by apoptosis based on binding affinity and avidity between the TCRs and self-peptide:MHC complexes. After T cells mature, they can also be tolerized in the periphery in many other ways, …

Peripheral Nerve Macrophages And Their Implications In Neuroimmunity, Peter Leon Wang

Arts & Sciences Electronic Theses and Dissertations

Macrophages are innate immune cells that protect against pathogens and maintain tissue integrity. In vertebrates, macrophages reside in every tissue where they perform specific functions from early development through adulthood. While macrophages provide important functions across all tissues, a major focus in recent years has been the role of resident brain macrophages, known as microglia, in neurodegeneration. As microglia have been shown to affect brain development, homeostasis, and disease, they demonstrate how immune cells critically mediate neurological health and point to the broader significance of neuroimmune interactions, or the coordinated actions of the nervous and immune systems for maintaining tissue …

Examining Early Interactions Between Innate Airway Resident Immune Cells And Mtb-Specific Factors During Pulmonary Infection With Mycobacterium Tuberculosis, Micah D. Dunlap

Arts & Sciences Electronic Theses and Dissertations

Mycobacterium tuberculosis (Mtb) is the leading cause of death by an infectious agent in the world today, infecting roughly one quarter of humans. Despite this, the mechanisms of early pathogenesis and host protective innate immune responses remain poorly understood and uncharacterized.

Lung resident Alveolar Macrophages (AMs) are the first host contact with Mtb bacilli after inhalation and are thus key mediators of the early pulmonary immune response. AMs are generally believed to reside entirely in the airway, but it was recently demonstrated that they have the capacity to egress and enter into granulomas during pulmonary infection with hypervirulent Mtb. Furthermore, …

Norepinephrine Induces Macrophage Polarization Critical To Eliciting Renal Fibrogenesis, Hannah Manoj

Undergraduate Research Symposium Posters

Renal denervation before ischemic injury has been shown to protect against fibrogenesis and the inflammatory response, which are two causes for the progression of chronic kidney disease. However, the administration of norepinephrine (NE) to denervated renal systems induced fibrogenesis and inflammation after ischemic injury. Our previous data indicates that NE-mediated stimulation of the α2-AR receptors is responsible for regulating several of the processes implicated in fibrogenesis and inflammation, including the accumulation, migration, and infiltration of macrophages to the site of injury; this is especially relevant as macrophages have been implicated as one potential cause for the inflammatory response.

Recent studies, …

Characterization And Function Of Islet Antigen Presenting Cells During Nod Diabetes, Stephen Thomas Ferris

Arts & Sciences Electronic Theses and Dissertations

Here we characterized the initial antigen presenting cells (APCs) within the islet of Langerhans to ascertain their identity and functional role as it pertains to autoimmune diabetes. The activation of the adaptive immune system is induced by the innate immune system, and more specifically APCs. Therefore, it is crucial to identify the APCs that are initiating T1D in order to elucidate the break in tolerance and intervene in order to inhibit progression. We have found that there is a resident macrophage that is present in all strains of mice. This islet macrophage has a distinct transcriptional profile that is unique …

Iron Regulation Of Macrophage Responses To Uropathogenic E. Coli, Nana Kwame Owusu-Boaitey

Arts & Sciences Electronic Theses and Dissertations

Uropathogenic E. coli (UPEC) are the principal cause of urinary tract infections (UTIs), one of the most common infections globally. Given the rising incidence of antibiotic resistance among UPEC strains, there is an increasing need to better understand the host response to UPEC and to develop ways to harness the bladder innate immune response that clears infection. In response to infection, the host attempts to limit the ability of UPEC to access iron, a metal critical to UPEC survival. Innate immune cells known as macrophages are known to regulate iron homeostasis through the production of pro-inflammatory cytokines, though it remains …