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Title: Immune responses during jaagsiekte sheep retrovirus infection and development of ovine pulmonary adenocarcinoma
Author: Summers, Christina
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2002
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Jaagsiekte sheep retrovirus (JSRV) is the aetiological agent of sheep pulmonary adenomatosis (SPA), a contagious bronchioloalveolar carcinoma, which imposes a serious economic burden on the sheep farming industry. This study evaluated the immunological responses during experimentally induced JSRV infection and tumorigenesis in conventionally housed and specific pathogen free (SPF) neonatal lambs, and in adult field cases in the terminal stages of SPA. This study identified, for the first time, changes in cellular function in the peripheral blood of JSRV-infected animals by measuring the in vitro lymphoproliferative response to various mitogens. The presence of JSRV did not affect the level of response to phytohaemagglutin (PHA) and pokeweed mitogen (PWM) stimulation, but a reduced response to concanavalin A (ConA) was demonstrated in the JSRV-infected animals. The reduced response to ConA was detected prior to the diagnosis of clinical symptoms and was also evident in the terminal stages of SPA. The presence of JSRV also affected the mitogenicity of the mannose-specific, monocotyledonous Narcissus pseudonarcissus lectin (NPA). The level of proliferation was comparable between JSRV-infected and control lambs, but post-stimulation phenotyping revealed an altered phenotypic profile, with elevated numbers of T and B lymphocytes from JSRV-infected animals. Furthermore, the addition of exogenous mannnose completely inhibited NPA mitogenicity in control but not in JSRV infected lambs. It has been established that NPA possesses insecticidal properties, which could potentially increase pest resistance in transgenic crops. During this study we revealed that NPA mitogenicity is age-dependent in sheep, with no lymphoproliferative response detected in adult animals. This research was extended to include human subjects, and we have shown that NPA is slightly mitogenic for adult lymphocytes but that mitogenicity is increased more than sevenfold for lymphocytes purified from umbilical cord blood. These findings indicate possible physiological implications as a result of introducing foreign lectins into human and animal food sources.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available