Abstract
The aim of the current study was to investigate the pathogenesisis of M. bovis pneumonia, using novel vaccines, and correlating any pathological changes with immunological parameters, and to develop a reproducible experimental model of M. bovis infection in young calves. Four experimental infections and two laboratory investigations were carried out. The first study aimed to develop an reproducible model of M. bovis infection in young calves that mimics naturally occurring disease, and investigated the effect of immunising 18 calves with an M. bovis extract consisting largely of hydrophobic variable membrane lipoproteins (vsp). The calves were subsequently challenged, and killed at 14-16 days post inoculation (d pi). The results were disappointing, as the study failed to demonstrate a clear difference between principal and control calves. The variation in the response of calves within the immunised and control group may either have been due to the presence of pre-existing infection in the calves at the time of challenge, or to natural variation between calves. Nevertheless, this study formed the basis of a further investigation, which examined the relationship between immunodiagnostic indicators and the stage of lesion development, and describes the key stages of the disease process. Some of the weaknesses described in Chapter 3 were addressed. The majority of the calves were purchased directly from farms, and the age of calves was similar in all three Groups. However potential prior infection was again a complicating factor in interpreting results. In this second study, 24 calves were immunised, infected and subsequently killed between 3 and 27 dpi. This study suggested that priming the immune system with a hydrophobic M. bovis extract, shortened the advent of clinical disease and induced more severe lesions earlier in the disease process.A third study, involving nine calves, examined the effect of priming with a hydrophilic M. bovis extract. Although the pathological changes induced in all calves were limited in extent, the results suggested that vaccination with a hydrophilic M. bovis extract neither provided protection, nor enhanced disease.
A fourth study involving 18 calves investigated the effect of different routes of immunisation, and investigated the role of local immunity. Results of this fourth study were inconclusive as the lung pathological findings in several calves were inconsistent with the time span of the infection period. One possibility is that the immunising agent itself stimulated pathological changes in the lung; another, more probable explanation is that there were pre-existing lung lesions in these calves.
In all four experiments immunological parameters were measured and attempts were made to relate these to pathological changes. In none of the experiments could the peripheral immune response be correlated with pathological changes, and no difference in peripheral immune parameters was detected between calves with different degrees of pathological changes.
The calves in all four experiments, with their diverse genetic background, management history and potential exposure to other respiratory pathogens, were a realistic sample of the general calf population. Thus it would not be unexpected to see variation between calves, in the response to the same stimulus. Using gnotobiotic calves would have eliminated some of the variables seen in this experiment, and may have produced cleaner results. Alternatively increasing the number of calves in the experiments would have reduced the impact of anyone calf's result; however it would have been difficult to justify using larger numbers of animals in these experiments, and it would also have been logistically impossible.
A fifth study was undertaken to investigate whether any correlation could be identified between the expression of certain membrane vsp and pathological changes in the lung. Lung sections from 36 field cases of calf pneumonia and 31 experimentally infected calves were selected for immuno-histochemical examination. The criteria used for selection was a clinical history and pathological changes in the lung suggestive of M. bovis infection. All those selected had lung lesions, which, were suggestive of M. bovis pneumonia and M. bovis was identified in lung tissue by sandwich enzyme linked immunosorbent assay (sELlSA). Histopathological results demonstrated evidence of variation in expression of vsp's, and suggested that this variation is random and not correlated with pathological changes.
The final study concentrated on the local immune response, and the Iymphocyte populations recruited at various stages of disease development in seven experimentally infected calves. Results suggested that both the innate and the acquired immune response participate in the development of M. bovis induced lesions, and indicated a role for C04, COS, yc T cells, and B cells in the pathogenesis of M. bovis pneumonia.
| Date of Award | 2013 |
|---|---|
| Original language | English |
| Awarding Institution |
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| Supervisor | David Bryson (Supervisor) & Hywel J. Ball (Supervisor) |
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