W.D. Smith

Age immunity to Ostertagia circumcincta: comparison of the local immune responses of 4 1/2- and 10-month-old lambs.

In 2 experiments, the local immune response to infection with 50,000 O. circumcincta was monitored in 4 1/2-month-old previously infected lambs by following changes in the composition of gastric lymph. The previously infected lambs were partially resistant to the challenge in that they harboured a greater proportion of early fourth stage parasites and that the developing larvae recovered from them were distinctly shorter than those present in controls. They also exhibited a secondary local immune response in the gastric lymph consisting of increases in the output of lymphoblasts and IgA cells which peaked 3 to 5 days after challenge, followed by increases in lymph IgA and IgA anti-larval antibody on days 6 and 7. The size of the total IgA response in a sheep was highly correlated with the degree of stunting of its larvae, suggesting that IgA antibody can reduce the growth of developing Ostertagia. When compared with the results of 2 identically designed experiments carried out previously in 10-month-old sheep, the younger lambs were measurably less resistant to challenge and most aspects of the magnitude of the local immune response were significantly depressed, although the timing of the response was similar. It is suggested that this poorly developed ability to mount a secondary mucosal immune response may explain the relative failure of the younger lamb to develop resistance to gastro-intestinal nematodes.

Manifestations of resistance to ovine ostertagiasis associated with immunological responses in the gastric lymph

Groups of previously infected and worm-free sheep were serially killed up to 10 days after challenge with 50 000 Ostertagia circumcincta larvae. Two similar groups of sheep were killed 10 days after challenge with 1000 larvae. The previously infected sheep were resistant to the smaller challenge dose in that fewer, stunted worms were recovered from them than from controls. However, this resistance was not as marked as that observed in the previously infected sheep which received the large challenge, because proportionally fewer worms were recovered after the 50000 dose and the great majority of these were arrested at the early fourth stage. The gastric lymph ducts of 6 previously infected sheep were cannulated successfully and a marked local immune response was detected in 3 sheep which were challenged with 50 000 larvae. No response was detected in 3 cannulated sheep challenged with 1000 larvae. In the lymph of the 50 000 dose group, a temporary increase in pepsinogen activity suggested that a hypersensitivity reaction related to the presence of large numbers of mucosal mast cells began between 24 and 48 h after challenge. This was followed by marked increases in the cellular and IgA content of lymph, which reached peaks on days 3 and 6, respectively. It is suggested that the response detected in the gastric lymph reflected aspects of a local immune reaction in the abomasal mucosa and that this reaction accounted for the enhanced degree of resistance to the larger challenge dose.

Local immunity and Ostertagia circumcingta: Changes in the gastric lymph of immune sheep after a challenge infection

Immunity to Ostertagia circumcincta was demonstrated in 5 previously infected sheep which were killed 10 days after challenge with 50 000 larvae. This immunity was expressed as a reduction in the number as well as the degree of development of the surviving parasites compared with those found in 6 control sheep. Gastric lymph was sampled from the immune group from 2 days before till 10 days after challenge and a secondary local immune response was detected. The main features of this response were a large increase in cell output in the lymph, especially in lymphoblasts and IgA-containing cells, which reached a peak on day 4 or 5, followed by a ten-fold increase in IgA immunoglobulin and IgA anti-worm antibody which reached a peak 7 or 8 days after challenge. The timing of these events suggested that the cellular, but not the IgA, response could have been involved in a putative mechanism which caused arrested development, although both components could have been implicated in mechanisms which may have caused expulsion of developing larvae.

Studies on the local immune response of the lactating ewe infected with Ostertagia circumcincta

Changes in the flow and composition of gastric lymph were monitored in groups of lactating and non-lactating ewes which were repeatedly infected with Ostertagia circumcincta. As judged by faecal egg counts and worm burdens the lactating group was more susceptible than the non-lactating controls to the challenge infection. Increased amounts of pepsinogen as well as larger numbers of eosinophils and neutrophils entering the gastric lymph indicated considerable abomasal damage and inflammation in the lactating ewes. However, measurement of the flow of lymphocytes as well as the amount of IgA and IgA antibody in the lymph did not indicate that these aspects of the local immune response were impaired during lactation; in fact the output of IgA-containing lymphocytes as well as IgA itself was usually raised in the lactating sheep. Lymph flow was increased and lymph globulin concentrations proportionally decreased in lactating ewes, irrespectively of whether they were infected with worms. It is suggested that these changes were caused by the increase in voluntary food intake which occurs during lactation.

Local immunity and Ostertagia circumcingta: Changes in the gastric lymph of sheep after a primary infection

Some aspects of the kinetics of the primary local immune response to O. circumcincta were studied by monitoring the flow and composition of gastric lymph from 4 sheep for 3 weeks after infection with 50 000 larvae. A significant increase in the frequency of lymphoblasts in the lymph showed that all the sheep were responding immunologically to the parasites from day 8 onwards. However, considerable individual variation in degree and timing was evident in other aspects of the immune response; 2 animals responded with large increases in lymphocyte output which reached a peak on day 5 or day 10, whereas the main response in the other 2 sheep appeared to be inflammatory in nature, with large increases in lymph flow and eosinophil output which occurred during the third week of infection. No significant changes in the content of IgA or IgA anti-worm antibody were detected in the lymph, but pepsinogen concentrations were significantly raised from day 12 onwards.

Changes in the flow and composition of gastric lymph in sheep repeatedly infected with Ostertagia circumcincta

Abstract A technique is described for catheterizing the gastric lymph duct of sheep, together with a reinfusion apparatus which continuously samples the lymph. The flow and composition of lymph sampled from 9 worm-free sheep was compared with that of 6 sheep which had been repeatedly dosed with Ostertagia larvae and which were showing signs of resistance to reinfection. Lymph flow was increased almost 2-fold in the infected sheep, and although the concentrations of IgG and IgM were similar in both groups, the amount of IgA was significantly raised in the immune animals. The lymph:serum ratios for IgA, IgG and IgM were 2·69, 0·59 and 0·17, respectively, indicating that the bulk of IgA was locally produced. The rate of output of IgA was about 5 times higher in the infected group. Radioimmunoassays revealed large amounts of IgA and IgG anti-larval antibody in the immune lymph but IgM from both groups was bound to the antigen. Total lymphocyte output was about 1·5 times greater in the lymph of the infected sheep but the output of large cells was unchanged. IgA was the predominant type of immunoglobulin-containing cell in all sheep and the rate of output of these cells was raised about 9 fold in the infected animals. IgM- and IgG-containing cells were always relatively rare (

Centrifugation studies on the infectivities of cellular fractions derived from mouse brain infected with scrapie (Suffolk strain).

SUMMARY: Cellular components in homogenates of brain tissue from scrapieaffected mice have been separated by centrifugation in sucrose and caesium chloride density gradients with the objective of location of the scrapie agent and concentration of scrapie activity. Improvements in the relative activity of the fractions removed from sucrose gradients were small but recovery was high in the material sedimented through 0.88 M-sucrose. No peak of activity was observed in zones removed from a caesium chloride gradient and activity throughout remained strongly associated with particulate matter. Ultrasonic disruption had little effect on scrapie activity. Concentrated preparations of sufficient potency for characterization of virus particles by electron microscopy were not obtained. From various experimental evidence the scrapie agent, if a virus, appears to be of small size. The strong association of the agent with tissue debris suggests that the presence of a tissue component may be necessary in the experimental transmission of the condition.

Determination of the dosage-response curve of mice inoculated with scrapie.

Abstract The reproducibility of titration of scrapie activity in mice has been tested using as criteria the histological examination of affected brains six months after intracerebral inoculation. Although heterogeneity of response to the inoculum, derived from Suffolk sheep, is known to occur probit analysis of the data has demonstrated equality of variance of response in the titration groups tested according to these criteria. Titres should differ by at least 0·8 log unit to be significant.

Immunoglobulins, antibodies and inhibitors of parainfluenza 3 virus in respiratory secretions of sheep.

SummaryVirus neutralising and haemagglutination inhibiting (HI) activities were monitored in the serum, nasal secretions and tracheo-bronchial secretions of lambs infected with Parainfluenza virus type 3 (PI3). HI activity was found in the secretions of both control and infected lambs, whereas neutralising antibody was found only in nasal secretions from infected lambs. Fractionation revealed that most of the HI activity in the secretions was due to a large molecular weight protein which also inhibited the haemagglutination (HA) of Parainfluenza virus type 1 (PI1) and type 2 (PI2) and Newcastle disease virus (NDV). This inhibitory activity was partially sensitive to receptor destroying enzyme (RDE). IgA antibodies specific for PI3 were also found in the respiratory secretions. However no increase in IgA levels was detected in the nasal secretions of the infected lambs. It is suggested that in certain reports non-specific inhibitors present in the nasal secretions of calves, may have been confused with PI3 specific IgA antibody.