A study on variation in immune responses and protective mechanisms to Ostertagia circumcincta and their relationship with parasitological parameters in Scottish blackface sheep

The aim of this study was to examine the variation in immunological control of Ostertagia circumcincta, following natural exposure of sheep by grazing contaminated pasture, and relate this variation to that in parasitological parameters. Selection of sheep by faecal egg count resulted in different results in two consecutive years, in the first year those sheep with higher faecal egg counts had more adult female worms, in the second those sheep with higher faecal egg counts had longer, more fecund worms. These observations are consistent with earlier studies showing that faecal egg count is a function of worm burden and worm fecundity. Immunophenotyping of peripheral blood revealed that lymphocyte subset percentages are repeatable and that lymphocyte numbers were greater in grazing lambs. A negative association between worm burden and B cell percentage representation of peripheral blood lymphocytes was observed, possibly as a result of immune modulation, whilst immunophenotyping of cells from lambs given a deliberate challenge provided further evidence of immune-modulation by O. circumcincta. Following natural infection those sheep with a larger abomasal nodes had shorter worms, suggesting that the magnitude of the immune response was important. Proliferation assays emphasised the importance of the local immune response by showing that responses to antigen were greater in lymphocytes from local tissues. Lymphocyte responses were dependent on previous exposure. Negative associations were observed between worm burden and proliferative responses, and because there was no evidence of active control of worm burden the results also provided further evidence of immune modulation. Enumeration of mast cells and globule leucocytes showed that there was a marked increase in the density of these cells following exposure to O. circumcincta, and although there was no evidence that these cells were involved in the control of worm burden there was a relationship between the globule leucocyte density and worm length that suggest this cell type may have a direct role in restricting or controlling worm length. The observation that lambs were able to mount a vigorous mast cell and globule leucocyte response although there was no evidence that they were able to control worm burden raises the possibility that these cell types may have a direct role in the control of the O. circumcincta burden. Parasite specific IgA responses were investigated and shown to increase with exposure and a positive association was observed between worm burden and local IgA activity following deliberate infection. The study provided further evidence that parasite-specific IgA activity has a role in regulating worm length. In conclusion the work in this thesis demonstrated considerable individual variation in the mechanisms of immunological control and host protection. The results provided further evidence of the role of limiting worm length and fecundity in the genetic control of O. circumcincta. Many of the findings could best be explained by suggesting immune modulation of the host by the parasite. It is likely that further studies on how O. circumcincta attempts to modulate the immune response, and whether or not the host can resist these attempts, will greatly increase our understanding of the host-parasite interface