Browsing by Subject "Immune system"
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Item Cold water stress and immunological responsiveness(Texas Tech University, 1996-05) Howard, Kevin RAnimal models can advance the knowledge of how neuroendocrine-mediated host stress responses modulate immune cell function. These animal models can be used to evaluate whether immunological perturbations following exposure to acute and chronic stressors are of clinical significance in resistance to infectious and neoplastic diseases. In the present study, we evaluated parameters of immunological structure and function in mice exposed to cold water stress. We exposed young adult male BDFl mice to 4°C water for 1 minute at 0900 and 1600 on each of 4 consecutive days. The treatment regimen invokes a complex paradigm of anxiety, forced exercise and hypothermia. Glucocorticoid production was enhanced on days 2 (P=0.011) and 3 (P=0.026). Exposure to the cold water stress regimen did not result in atrophy of or leukopenia in the spleen or thymus. Single fluorescence flow cytometric analysis revealed profiles of CD3, CD4, and CD8 populations in the spleen and thymus were not altered following exposure to the cold water stress treatment. Exposure to the stressor inhibited concanavalin A (ConA)-stimulated lymphocyte blastogenic potential in thymocytes (P=0.024) but not splenocytes (P>0.050). Profiles of IL-2 production (P=0.031; as measured by ELISA), but not IFN production (P>0.050; as measured by bioassay) were altered by exposure to the cold water stressor. Exposure to the stressor did not inhibit profiles of immune responses to the immunogen cholera toxin binding fragment (CTB), as revealed by splenocyte proliferation, IL-2 and EFN production, and titers of anti-CTB antibody. Collectively, these results indicate that exposure to acute periods of cold water stress can result in mild immunomodulatory effects in mice which are not sufficient to impair response to the protein antigen CTB.Item Determining the interactions between serum proteins of the complement system and outer membrane proteins in avian pathogenic Escherichia coli(2017-11-08) Botero, Cindy; Lynne, Aaron M.Eschericia coli is a well-known member of the intestinal flora of mammals and birds. However, there exist pathogenic strains capable of causing disease. One strain comes from the O-serogroup of E. coli, APEC O2 (+/+), and causes millions of dollars of global losses annually. The elucidation of the mechanisms of complement avoidance in pathogenic strains could potentially provide vital information to understanding bacterial pathogenicity and assist in the future development of a vaccine. The bacterial strains used were APEC O2, an iss+/bor+ strain, and DH5α, a iss-/bor+ strain. Mutant strains were created from a knockout of iss in APEC O2 (+/+) to create APEC O2∆iss (-/+), and a knockout of the gene bor to create DH5α∆bor (-/-). In order to determine how Iss and Bor assist each other in surface exclusion tactics and in serum resistance, each strain was subjected to a complement consumption assay, which measured the amount of complement consumed by each strain, the bactericidal assay, which determined the amount of cell death in response to complement, ELISA, which measured the amount of terminal complement complex remaining after exposure of bacteria to serum, and immunofluorescent microscope visualization, which visually showed the bound C5b-9 terminal complement complex to the outer membrane of the bacterial strains. The results of this study determined that the role the protein Bor has on assisting Iss with serum resistance may not be as significant as previously thought. There may also be something other than the gene bor assisting iss in the prevention of cell death due to the attachment of membrane attack complex (MAC) on the cell wall. This study expands on our previous understanding of how proteins of the outer bacterial cell membrane cooperate in order to provide resistance to complement proteins in the immune system.Item Dietary lipid modulation of immune parameters in burn and sepsis(Texas Tech University, 1994-12) Penturf, Mary Ellen HiseTwo experiments were conducted to obtain further information on dietary lipid modulation of immune function in metabolic stress conditions. In the first experiment, the objective was to modify dietary lipid composition of animal diets in order to evaluate plasma membrane changes and immunological parameters during sepsis. The second experiment was conducted to determine the effect of an essential fatty acid deficient diet on immunological response during postburn injury.Item Immunomodulation of macrophage function by recombinant human myeloperoxidase(Texas Tech University, 1995-12) Castro, AaronRegulation of the immune response is necessary for protection of the host as well as the avoidance of autoimmune diseases. The regulation of macrophage function by myeloperoxidase is a previously unrecognized function of this enzyme. A recombinant form of myeloperoxidase, an enzyme commonly found in neutrophils, was used to study the effects of this enzyme on certain macrophage capacities and functions. Both neutrophils and macrophages are present at the site of either inflammation or infection. Stimulation of macrophages by pathogens such as bacteria and fungi, results in production of reactive oxygen intermediates. This study showed that myeloperoxidase induced the production of these reactive oxygen intermediates. Myeloperoxidase was shown to increase the uptake and subsequent killing of a common fungal pathogen, Candida albicans, demonstrating its ability to alter the macrophage response. In addition, these same intermediates act on surrounding tissue and cause damage observed with diseases such as rheumatoid arthritis. The interaction of myeloperoxidase and macrophages at the site of inflanunation could result in the observed chronic inflammatory state seen in rheumatoid arthritis patients. Studies by other investigators have detected myeloperoxidase in the synovial fluids of patients with rheumatoid arthritis. Evidence for the establishment of macrophage-mediated chronic inflammation was provided by studies demonstrating the de novo synthesis and secretion of cytokines by macrophages after exposure to myeloperoxidase. The production of macrophage-derived cytokines, which are powerful mediators of inflammation as well as the immune system, provides further evidence for the macrophage myeloperoxidase interaction in chronic inflanmiation. The role of myeloperoxidase in mediating the immune response, both in a protective function as well as a potentially destructive role, is novel in the study of chronic inflammation.Item The role of aging T-lymphocytes in prostate cancer development(2014-12) De Angulo Soriano, Alejandra; DeGraffenried, Linda; Jolly, Christopher A; Daniel, Benjamin A; Sanders, Bob G; Sun, LuZheAge is the single greatest factor associated with increased risk for prostate cancer development. Evidence implicates progressive age-related immune dysfunction with increased prostate cancer incidence. The aged T cell response is characterized by increased production of pro-inflammatory cytokines, which could significantly contribute to prostate tumorigenesis through induction of key pro-survival factors. The objective of these studies was to determine how age-related changes in T-lymphocyte function contribute to prostate tumorigenesis. The hypothesis that age-related changes in T-lymphocyte function to a pro-inflammatory phenotype promote prostate cancer development was tested using the glycerol-3-phosphate acyltransferase-1 (GPAT-1) knock-out mouse, which mimics many of the characteristics of an aged immune system. T cells from old (24-month) mice and aging-mimic T cell GPAT-1 [superscript -/-] mice generate more pro-inflammatory cytokines than T-lymphocytes from wild type mice. These cytokines turn on inflammatory pathways that stimulate proliferation, tissue disruption, and tumor growth. Initial studies showed that secreted factors from aging and T cell aging mimic GPAT-1 [superscript -/-] mice produce circulating factors that induce pro-inflammatory pathways in prostate cells, most notably the nuclear factor kappa-light-chain-enhancer of activated B cells (NF- [subscript K] B). Additionally, results from recent experiments demonstrate that serum from the GPAT-1 [superscript -/-] mice induce protein expression of downstream targets of NF- [subscript K] B in the prostate, most notably factors that induce macrophage infiltration and key pro-survival proteins. Furthermore, my experimental results suggest that the increased production of interleukin 17 (IL-17) by aged T cells play a role in the induction of proinflammatory pathways in the prostate. Based on these findings additional studies were design to determine if the increased production of pro-inflammatory cytokines by aging T-lymphocytes contributes to a more malignant phenotype in the prostate. Finally, the inter-relationship between an aging immune system and the aging tissues in the body was explored. Findings from these studies provide evidence that the dysregulation of cytokine production seen in aged T cells may directly contribute to the increased risk for prostate cancer in the elderly. This new perspective regarding the role of the aging immune system in cancer development opens new avenues for development of potential preventive interventions and screening biomarkers.Item T-cell activation by ethanol: a possible mechanism for immunosuppression(2007-12) Naqvi, Hassan Raza, 1976-; Poenie, Martin F.Alcohol abuse has been commonly associated with enhanced susceptibility to pathogens. Studies on the effects of ethanol on the immune system are complicated by a lack of consensus on whether ethanol activates, inhibits or has no effect on immune cells. We present data showing that acute exposure of T cells to ethanol elicits responses that broadly parallel responses seen in normally stimulated T cells such as the formation of the immune synapse, polarization of the microtubule organizing center (MTOC) to the synapse and tyrosine phosphorylation of signaling proteins as seen when the T cell Receptor (TcR) engages antigen-MHC. However, incomplete activation of the T cell signaling program leads to unresponsive or anergic T cells. Our data suggests the hypothesis that ethanol can activate T cells in a manner that leads to anergy. We have found that ethanol triggers calcium signaling and this has provided one of the primary tools for analyzing the effects of ethanol on T cells. Ethanol induced calcium transients are dose-dependent and are comparable to those triggered by low doses of anti-TcR antibody. This is important because it allows us to compare ethanol dependent signaling to that normally triggered through stimulation of the T cell receptors. Analysis of the calcium signaling pathway indicates that ethanol-stimulated calcium transients depend on calcium entry and are likely due to opening of CRAC type calcium channels. The observed calcium transients go a long way towards explaining how ethanol may stimulate T cells and provides a mechanism for immune suppression through the observed translocation of NF-AT in ethanol pulsed cells. The translocation of NF-AT is particularly important because of reports that it plays a crucial role in triggering anergy and immunosuppression. Taken together, these data can help explain how ethanol can both activate T cells and cause immunosuppression.