Some factors affecting the immune response to helminth infections

Sivanathan, Sivaja (1982) Some factors affecting the immune response to helminth infections. PhD thesis, University of Glasgow.

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The original objective of this study was to investigate further, the observation of Benitez-Usher and his colleagues (1977) that when an anthelmintic was administered shortly after each of two immunising infections of irradiated Haemonchus contortus larvae lambs failed to express any immunity to subsequent challenge with normal larvae. Unfortunately this aim was not achieved due to the fact that the H. contortus irradiated larval vaccine failed to confer protection to subsequent challenge. This result was totally unexpected as in all previously published reports a similar regimen of vaccination was highly successful. Following this finding it was decided to undertake an investigation of the reasons for the failure of the H. contortus larval vaccine (Section 1) and to use the rat/Nippostronqylus brasiliensis model system to study the original objective i.e. the effect of anthelmintics on the immune response (Section 2). In examining the possible reasons for the failure of the H. contortus vaccine, the following factors were considered to be most likely. Firstly, a technical error in the preparation of the vaccine: this was discounted due to the fact that on retrospective checking no errors could be detected. In addition, a research scientist in another institute was found to be currently experiencing similar difficulties with the larval vaccine despite previous success. The second possibility was that the larvae, due to continuous passage under laboratory conditions, had developed an increased radiosensitivity leading to over-attenuation with resultant loss of both infectivity and immunogenicity. This seemed unlikely since the worm burdens of the vaccinated groups contained significant numbers of sterile female worms derived from the irradiated larvae. Also, no increased radiosensitivity was observed in an irradiation dose titration experiment in which larvae were irradiated at 40 kr and 60 kr in a 0Co source and administered on a single occasion. to lambs. The resultant number of sterile female worms found at necropsy of these lambs v/hen compared with the original vaccine studies carried out in the 1960's, did not indicate any change in the radio-sensitivity of the larvae. The third possibility that the Glasgow strain of H. contortus had lost its immunogenicity was then examined. It was found in two experiments that infection with normal larvae failed to confer the anticipated degree of protection against challenge. It seemed therefore that the strain had lost its immunogenicity, although this conclusion must be tempered by the fact that small groups of lambs were used in these experiments. Subsequent studies were concerned with a comparison of larvae irradiated at 40 kr and 60 kr in either a 0Co source or an X-ray unit. It was found that irradiation at 40 kr from either source completely restored the immunogenicity of the vaccine to that previously reported i.e. around 95%. However, in the final experiment, irradiation at 60 kr also produced a successful result in that the challenge worm burdens were reduced by 76%. Future experiments are necessary to establish the reason for the inconsistency of the 60 kr vaccine but it is suggested that irradiation at 60 kr is perhaps borderline for the retention of immunogenicity: it is also possible that this variation in results might be associated with the physiological state and innate infectivity of various batches of larvae before being subjected to irradiation. (Abstract shortened by ProQuest.).

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Additional Information: Adviser: J L Duncan
Keywords: Animal diseases, Pharmacology, Parasitology
Date of Award: 1982
Depositing User: Enlighten Team
Unique ID: glathesis:1982-71982
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 17 May 2019 13:32
Last Modified: 17 May 2019 13:32

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