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The Enzymatic Function Of The Tir Domain: From Axon Degeneration To Innate Immunity, Kow Essuman
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 …
T Cell Immunity In Pancreatic Cancer Is Undermined By Dendritic Cell Dysfunction, Samarth Hegde
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+ …