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Title: Immune responses of sheep to Psoroptes ovis (sheep scab mite)
Author: Van den Broek, Adrianus Hendrikus Marinus
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2003
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Studies were conducted to investigate the immunopathogenesis of cutaneous lesions in sheep scab. The initial studies examined the nature and temporal development of the lesional infiltrate and growth during experimental primary and challenge infestations of sheep with Psoroptes ovis. These demonstrated that granulocyte infiltration was dominated by eosinophils, accompanied by mast cell hyperplasia and degranulation and dermal edema, features characteristic of IgE-mediated Type I hypersensitivity reactions. In primary infestations eosinophil counts and epidermal and dermal pathology were maximal 9 weeks after infestation while in challenge infestations eosinophil counts fell rapidly 3 weeks after challenge, an observation consistent with failure of the mites to become established. Importantly, within 24 hours of primary infestation P. ovis had provoked an intense eosinophil infiltrate and marked degenerative and proliferative epidermal pathology. Immunohistochemistry of primary infestations revealed a massive lesional infiltration of CD4+ and CD45RA+ cells that was accompanied by smaller numbers of y§ T cells and dendritic cells. In primary infestations, lesional growth was exponential during the first 7 weeks and then plateaued. In challenge infestations lesional growth was significantly reduced (p< 0.001), an observation indicative of the development of a substantial protective immunity. Alterations in haematology and serology were investigated in parallel with the initial studies of lesional histopathology. In primary infestations eosinophilia developed in all sheep and basophilia in 6/14 sheep but after challenge infestation basophilia was not detected and eosinophilia was recorded in only one animal. Analysis of isotype-specific antibodies indicated that P. ovis elicited antigen-specific IgG, IgM and IgE but apparently not IgA responses and that challenge infestations provoked a significant (p<0.01-0.03) amnestic IgE but not IgG or IgM antibody response. Detection of P. ovis antigen-specific IgE provided further evidence of the involvement of immediate hypersensitivity in the immunopathogenesis of cutaneous lesions but a significant rise in antigen-specific IgE level was not detected until late (7 weeks) in the course of primary infestation. SDS-PAGE/Western blots demonstrated that P. ovis antigens/allergens >100kD were labelled most consistently by IgG/IgE antibodies and that the number of antigens/allergens recognised and the intensity of labelling increased with time after infestation. Intradermal skin tests demonstrated the occurrence of immediate hypersensitivity, late phase (LPR) and delayed-type hypersensitivity (DTH) reactions to P. ovis whole-mite extract. Histopathology ofthe LPR and DTH indicated that both responses, but particularly the DTH, were dominated by eosinophils. Prausnitz-Kustner tests demonstrated the IgE dependence ofthe LPR and that the DTH was not transferred by a serum factor. Examination of the temporal development of these hypersensitivity responses indicated that they were not manifested until late in the course of infestation. This research has demonstrated that P. ovis provokes an intense eosinophil dominated innate response, an IgE-mediated Type I reaction and eosinophil dominated late phase and non-classical DTH reactions and that in addition, it generates a significant protective immune response.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available