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Title:   Author  item
                                            Palmer, Mitchellitem
                                            Waters, Wadeitem
                                            Thacker, Tyleritem
                                            Whipple, Diana
  Submitted to: International Conference on Mycobacterium bovis
                                    Publication Type: Abstract Only
                                    Publication Acceptance Date: 8/22/2005
                                    Publication  Date: 8/22/2005
                                    Citation: Palmer, M.V., Waters, W.R., Thacker, T.C., Whipple, D.L. 2005. Lesion Development and Immunohistochemical Changes in Cattle Experimentally Infected with Mycobacterium bovis [abstract]. International Conference on Mycobacterium bovis. p. 70.Interpretive Summary:
                                Technical Abstract: Mycobacterium bovis, the causative agent of bovine tuberculosis is known to persist within granulomas, distinct lesions represented by a caseonecrotic core surrounded by epithelioid macrophages, T-lymphocytes, B-lymphocytes, Langhans-type multinucleated giant cells and fibroblasts. Formation of granulomas involves a complex array of immune activation and cellular migration. To examine temporal changes in granuloma development, 32 cattle were inoculated with M. bovis. Tissues from four calves each were examined microscopically at 2, 4, 6, 8, 12, 24, 36 and 52 weeks after inoculation. Immunohistochemistry for iNOS, CD68, CD4, CD8 and gamma/delta T-lymphocytes was performed. Immunoreactivity for iNOS was present with the appearance of the first microscopic lesions at PID 28. iNOS positive cells consisted of epithelioid macrophages and multinucleated giant cells surrounding central areas of caseous necrosis. Abundant iNOS immunoreactivity was associated with granulomas through PID 90, but was minimal from PID 180 to the termination of the experiment. CD68 positive cells were a prominent feature of granulomas at all time-points examined. Lesions at all time-points contained large numbers of CD4+ T-lymphocytes with lesser numbers of CD8+ T-lymphocytes and few gamma/delta T-lymphocytes. The relative number of different lymphocyte subsets remained constant throughout the experiment. Nitric oxide (NO), the product of iNOS, and other related nitrogen intermediates are powerful oxidants. Activated macrophages producing NO are capable of killing members of the M. tuberculosis complex. Diminished expression of iNOS late in the progression of bovine tuberculous granulomas may represent a failure of the host response to control infection.


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