Gnotobiotic lambs were protected against rotavirus infection by the presence in the gut at the time of infection of colostrum or serum containing antibodies to rotavirus. This protection was observed even when passively-acquired antibody was not present in the serum of the infected lamb. Infection under these conditions may have conferred immunity to subsequent challenge.

Summary1. Acute systemic anaphylaxis in calves was characterized by marked systemic hypotension; hypertension in the pulmonary arteries and abdominal vena cava, and transient apnoea. Calves responded with a second reaction to antigen, but a third anaphylactic response could not be evoked. 2. Suppression of systemic anaphylaxis could not be effected with mepyramine, whereas methysergide or diethylcarbamazine each suppressed anaphylaxis by 50%. Disodium cromoglycate alone did not inhibit anaphylaxis: however, when disodium cromoglycate was combined with diethylcarbamazine almost total suppression (85%) was achieved. Sodium meclofenamate also was a powerful inhibitor of anaphylaxis (80%). It is tentatively suggested that slow reacting substance (SRS-A) may be an important mediator of bovine anaphylaxis. 3. Bilateral vagotomy did not modify the circulatory responses to injected histamine, 5-hydroxytryptamine (5-HT) or antigen, whereas the effects of these agents on ventilation (apnoea) were abolished by vagotomy. 4. Plasma histamine concentration was increased during anaphylaxis, whereas plasma 5-HT was not. Whole blood histamine concentration fell sharply and remained depressed during 20 min of anaphylactic shock. Reduced whole blood histamine levels probably reflect the severe leucopoenia in the calves. 5. Histamine concentrations in six tissues taken from calves subjected to anaphylaxis were not different from those in control calves; mast cells were of similar numbers to controls, but showed some swelling, granular spilling and metachromasia.6. Histamine, 5-HT, bradykinin and antigen caused increased pulmonary artery perfusion pressure and ventilation resistance in isolated lungs from sensitized calves. However, there was no difference in histamine and 5-HT concentration in perfusates obtained during antigen infusion of sensitized and control lungs. 7. Systemic anaphylaxis of calves may result from the interaction of histamine, 5-HT and SRS-A. The present data implicate (by indirect measurement) SRS-A as an important mediator of anaphylaxis in this species.

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The level and specificity of antibody responses elicited in cattle by irradiated non-infective Trypanosoma brucei were examined and related to the development of protective immunity. These responses were compared with those induced by infection and by inoculation with purified variable surface glycoprotein (VSG) in adjuvant. It was found that 10(7) or more irradiated trypanosomes inoculated intravenously into cattle conferred complete protection against challenge with 10(3) homologous trypanosomes 14 days later. Animals immunized with 10(6) organisms showed partial protection. Of the assays used for detection of antibody, neutralization of infectivity was slightly more sensitive than either the Farr assay or the immunofluorescence test which were both more sensitive than solid-phase radioimmunoassay (RIA). Detection of specific antibody correlated with immunity, in that all animals inoculated intravenously with 10(6) or more trypanosomes developed neutralizing activity in their sera. The antibody responses after intravenous inoculation were consistently superior to those induced by the subcutaneous route. By carrying out blocking assays, most of the antibody elicited by irradiated trypanosomes was found to be specific for antigenic determinants on the VSG exposed on the surface of live trypanosomes. A similar specificity was found for the antibody induced during infection with T. brucei. Conversely, a large component of the antibody induced by purified VSG in adjuvant appeared to be directed against determinants on the VSG which are not exposed on live trypanosomes and are probably not involved in protective immunity.

To examine the influence of an established infection on subsequent challenge with another unrelated trypanosome serodeme, cattle were subjected to two challenges, 5 to 6 wk apart, with unrelated isolates of Trypanosoma congolense. The primary infection inhibited the establishment of the second infection despite the initial absence of detectable antibody to the trypanosomes used for the second challenge. This was true whether the second challenge consisted of bloodstream forms of the parasite or metacyclics from infected Glossina m. morsitans. Rechallenge with bloodstream forms resulted in a slight antibody response, which was only detectable by immunofluorescence and was much less than in the challenge controls. Although animals subjected to the second challenge by tsetse flies showed no appreciable increase in parasitemia and, in most instances, no chancre reaction at the site where the tsetse bit, they developed readily detectable neutralizing antibody to the metacyclic trypanosomes. That this interference effect was not the result of specific immunity and required an active infection was confirmed by the finding that when infected animals were treated with Berenil prior to rechallenge, they were fully susceptible to the infection.

A human stool filtrate containing rotavirus which was administered orally to gnotobiotic lambs caused diarrhea, virus excretion, development of antibodies to rotavirus, and pathological changes in the villi of the small intestine. Thus, lambs may serve as experimental animals for the study of human rotavirus infections. This model system was used to study passive protection. Human immunoglobulin G (IgG) containing antibody to rotavirus was fed to lambs 24 to 78 h after birth, and the lambs were infected with lamb-passaged human rotavirus when 30 h old. The lambs treated with IgG did not develop diarrhea, and virus excretion was delayed in onset and shortened in duration. It may be possible to make similar use of IgG to protect children at risk in a rotavirus outbreak. The treatment did not prevent the lambs developing antibody to rotavirus.

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