Browsing by Subject "Department of Veterinary and Biomedical Sciences"
Now showing 1 - 3 of 3
Results Per Page
Sort Options
Item In situ analysis of perforin expression in SIV-specific CD8 T cells in tissues from rhesus macaques vaccinated with live-attenuated SIVΔnef and challenged with SIVmac251(2011-04-13) Wagstaff, ReeceHuman immunodeficiency virus (HIV) was identified as the cause of acquired immunodeficiency syndrome (AIDS) in the 1980s, and since then it has proliferated into one of the most vexing pandemics of its time, if not all of human history. As of today, there is still no known cure for HIV, although numerous strategies are currently being pursued to confer immunity. Vaccines represent one of those strategies, and are a plausible method for bestowing resistance to HIV and other lentiviruses. Currently, research exists to show that attenuated vaccines created from simian immunodeficiency virus (SIV), an HIV analogue present in simians such as the Rhesus Macaque, provide suitable resistance for that disease in the simian model. Being that the SIV genome is sufficiently similar to the HIV genome, there is a good probability that an attenuated vaccine created from HIV could produce comparable immunity in humans, however, the mechanism by which SIV vaccines confer resistance is still not well understood and needs to be studied further if attenuated HIV vaccines are ever to be presented in human clinical trials. My hypothesis is that an early, robust, SIV-specific CD8 T cell response in lymph nodes and in the site of infection is responsible for the protection induced from live-attenuated SIV vaccines. To test this hypothesis I quantified perforin assays in lymphatic tissues of immunized macaques that have been challenged with pathogenic SIV. The assays were created by immunohistochemistry staining techniques, including in-situ tetramer staining, and evaluated via scanning confocal microscopy.Item The location, abundance, and proliferation status of SIV-specific CD8 cells in rhesus macaques vaccinated with live attenuated SIVΔnef and challenged with the pathogenic SIVmac251(2011-04-13) Nguyen, Tammy TranOver 30 million people are infected with HIV/AIDS today. There is an urgent need to develop an effective vaccine. Simian immunodeficiency viruses (SIVs) in rhesus macaques serve as a valuable animal model of HIV infection. Live attenuated SIVs provide protection in SIV infected rhesus macaques challenged with highly pathogenic SIV. The goal of this experiment is to identify correlations of protection that is provided by SIVΔnef vaccination. Here I determined the abundance, location and activation/proliferation status of SIV-specific CD8 T-cells in lymph nodes and spleen from SIVΔnef vaccinated rhesus macaques before and after challenge with the pathogenic SIVmac251. Confocal images were obtained from tissues stained with MHC-tetramers that stain SIVspecific CD8 T cells and Ki67 antibodies that stain proliferating cells and activated T cells. We found similar numbers of SIV-specific CD8 T cells, and similar percentages of SIV-specific CD8 T cells before and after challenge. These results demonstrate that 1) SIV-specific CD8 T cells were present in lymphoid tissues at the time of challenge, and 2) no expansion of SIV-specific CD8 T cells in lymph nodes and spleen was required for protection. This study yields insights into CD8 T cell responses that are likely needed to be induced by a successful HIV vaccine.Item Role of CD38/cyclic-ADP-ribose in Human Asthma(2009-04-08) Smelter, Dan F.CD38 is a cellular protein found throughout the mammalian body. It is involved in calcium signaling and innate immunity. Its expression is augmented by the presence of multiple contractile agonists that occur in the development of asthma, and it is implied that CD38 expression is involved in the pathogenesis of asthma. However, CD38's role in human asthma has not been described. In my studies, I wanted to determine whether CD38 expression is involved in human asthma. To test this, I studied the effects of TNF-alpha-induced augmented CD38 expression in airway smooth muscle cells obtained from asthmatics compared to non-asthmatics. Also, I tested the intracellular calcium response to contractile agonists in cells from asthmatics and non-asthmatics following exposure to TNF-alpha.