We have developed an experimental infection model in which previously infected yearling sheep acquired a MK-2206 clinical trial substantial degree of protective immunity to T. circumcincta compared to naïve animals undergoing a primary infection (5,10,14,15). In this paper, we have repeated these experiments in 5-month-old lambs, to compare the responses of the two age groups. This investigation was motivated by the fact that age-related immunity to gastrointestinal nematode parasites has been widely documented in sheep, yet the underlying reasons are poorly understood. Thus, compared to adult sheep,

lambs develop impaired immunity to natural nematode infections or following immunisation with irradiated larvae (16–22), despite being capable of mounting protective immune responses to a variety of vaccines including ones containing nematode intestinal antigens (23). More specifically, prior experiments with a very similar Teladorsagia/gastric lymph model showed that young lambs were more susceptible than yearlings to infection and mounted measurably lower secondary immune responses (5,11). Two experiments were carried out involving Daporinad cell line a total of 66 lambs aged 5 months at time of challenge. All had been reared indoors

under conditions designed to exclude accidental infection with nematode parasites. Infective larvae were from an anthelmintic susceptible T. circumcincta isolate which had been passaged through sheep at Moredun Research Institute

for a number Bumetanide of years. Larvae were stored for up to 1 month at 4°C prior to administration. All infective larvae used within each experiment were derived from the same batch. The common gastric lymph duct, which contains efferent lymph draining all four stomachs, was cannulated as detailed elsewhere (24). The sheep were fitted with an indwelling venous catheter placed in the posterior vena cava. Collection, sampling and re-infusion of lymph, and post-mortem procedures were carried out as previously reported (10). Worm counts were carried out as detailed elsewhere (10). A random sample of approximately 50 parasites obtained from each animal killed on day 10 of Experiment 6 was measured by a Camera Lucida under 10× magnification. Sexually undifferentiated worms measuring <1·5 mm were classified as EL4, longer parasites were designated developing worms. Arithmetic means with standard errors are shown throughout. Parasite counts and percentage EL4 were compared by Student’s t-test. Frequency distributions of male and female worm lengths were made for individual sheep and group means were calculated from these. Immunoglobulin concentrations and cell numbers were compared using Student’s t-test, and, after log transformation, by repeated measures (Genstat).