Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.776450
Title: Studies on the mechanism of anaphylaxis in cattle
Author: Aitken, Maureen MacKenzie
Awarding Body: University of Glasgow
Current Institution: University of Glasgow
Date of Award: 1970
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Abstract:
Although hypersensitivity may play a part in diseases of cattle the mechanisms of hypersensitivity reactions have been investigated in detail only in laboratory animals and the relative importance of endogenous pharmacologically active substances, namely histamine, 5-hydroxytryptamine, kinins and SRS-A in such reactions has been found to vary in different species. Ayrshire and Friesian calves were sensitised to ovalbumin and horse serum. One intravenous injection of ovalbumin was adequate but two, separated by an interval of 7 hays, were required of horse serum. Challenge by intravenous injection of the appropriate antigen after a latent period of at least 7 days, resulted in the immediate onset of acute systemic anaphylaxis from which animals either died within 10 min. or recovered in most cases within 50 min. to 2 hr. Anaphylaxis was characterised by respiratory distress, coughing, apnoea, systemic hypotension, pulmonary hypertension, bradycardia, leucopenia, neutropenia and haemoconcentration. Necropsy revealed severe pulmonary oedema, emphysema and intra-alveolar haemorrhage. Diarrhoea occurred 48 to 72 hr. after non-fatal reactions. The severity of the symptoms depended on the challenge dose. A course of weekly intramuscular injections of ovalbumin with complete Freund's adjuvant also resulted in sensitisation to ovalbumin. Animals sensitised in this way showed similar symptoms on challenge but reacted to doses of ovalbumin 50 times smaller. These animals also reacted non-specifically on challenge with horse albumin or horse serum. Administration of histamine, 5-hydroxytryptamine or bradykinin produced effects similar to those of anaphylaxis. 5-Hydroxytryptaraine differed in that even lethal doses did not result in pulmonary oedema. All the effects of these substances were reduced in the presence of their specific or selective antagonists with the exception of the apnoeic effect of 5-hydroxytryptamine which persisted in the presence of methysergide and BW5OIC67. Vagotomy did not alter the effects of histamine or 5-hydroxytryptamine. In vitro bovine tracheobronchial smooth muscle and pulmonary vascular tissue contracted in response to histamine, 5-hydroxytryptamine and bradykinin. These responses were abolished by the appropriate antagonists. Vascular perfusion rate of isolated lobes of lung was reduced and air perfusion pressure increased by these substances. Apart from a reduction in lacrimal secretion no modification of anaphylaxis was observed in animals pretreated with antihistamines or atropine. Meclofenaraate, a selective antagonist of kinins, SRS-A and ATP prevented the respiratory changes and reduced the circulatory changes in animals sensitised without Preund's adjuvant. This suggested that kinins and/or SRS-A and ATP might be important as mediators. The compound BW5OIO67, had a modifying effect on anaphylaxis. However, this appeared to be unrelated to its activity as an antagonist of 5-hydroxytryptamine. The occurrence of apnoea during anaphylaxis was prevented or delayed in vagotomised animals. Haematological changes were unmodified after pretreatment with antagonists. The protective effect of meclofenamate, in animals sensitised using Freund's adjuvant, was limited to inhibiting mild reactions only. Responses of pulmonary tissues to antigen in vitro were shown Oiily by tissues removed from animals sensitised using Freund's adjuvant, Schultz-Dale reactions were elicited from intestinal tissue of animals sensitised without adjuvant. Antigen failed to release histamine in vitro from chopped lung, pleura or liver capsule of sensitised animals. Some release of histamine from chopped skin did occur. Concentrations of histamine in the tissues of animals which died during or after anaphylaxis tended to be higher than in control animals. Plasma free histamine levels were elevated following anaphylaxis but serial blood samples showed great variation in plasma histamine levels. Perfusion of isolated lung with ovalbumin resulted in the presence of histamine, bradykinin and possibly other spasmogenic substances in the perfusate. Perfusate from the lungs of sensitised animals had a higher content of active substances than did that from the lungs of unsensitised animals. Serum of animals sensitised using Freund's adjuvant had the property of sensitising the skin of other calves for PCA which could.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.776450  DOI: Not available
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