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Title: The role of granuloma formation in immunological adjuvance : an analysis of the cellular composition of, germinal centre formation in, and antibody production by granulomata induced by Freund's adjuvants in the chicken
Author: Smithyman, Anthony Meiklejohn
ISNI:       0000 0001 3469 3288
Awarding Body: University of Glasgow
Current Institution: University of Glasgow
Date of Award: 1977
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The nature of the granulomata which are induced at the site of an injection of Freund's complete adjuvant, FCA (dead tubercle bacilli in mineral oil) containing an added antigen (HSA) were studied the domestic fowl in relation to the adjuvant effect on antibody formation. The granulomatous lesions were induced in the pectoral muscle of the birds and examined at periods from one to twenty weeks and contrasted with granulomata resulting from injection of Freund's incomplete adjuvant, FIA, (antigen suspended in mineral oil). The cells forming these granulomata were studied in detail. As noted by authors working in other species (Spector and Lykke, 1966; Smith et al 1970) the FCA granuloma is first dominated by emigration and proliferation of macrophages. This is followed by a gradual infiltration of lymphocytes, and plasma cells in an organised fashion so that the granuloma may come to resemble normal peripheral lymphoid tissue with "post-capillary venules", and primary lymphoid follicles and in the chicken occasional germinal centres and extensive antibody production. almost as if the granuloma had become a lymph node analogue. One finding which has not been previously recorded was the extent to which germinal centres are involved in these processes. It was found that while local germinal centres were rarely if ever found in FCA granulomata beyond one week, FIA granulomata contained increasing numbers of large, well-defined germinal centres. This argued an important role for germinal centres in local sites. There seemed to be an inverse relationship between the number of germinal centres present and the level of circulating anti-HSA antibody observed. Based on this observation the second part of this thesis examined the role of germinal centres in the immune response of the chicken, both in the spleen and in ectopic sites such as the granuloma. The results were tested against the hypothesis that germinal centres are involved in the feedback control of antibody biosynthesis, and the suggestion that the destruction or interference of germinal centres by the mycobacterial component of Freund's complete adjuvant is responsible for the abnormally high,late,or second phase, circulating antibody levels observed in FCA-treated animals. It was concluded that the main adjuvant effect of FCA on the bird is a new and delayed biosynthesis of antibody (to HSA) derived from plasma cells and their precursors within the large epithelioid-cell granuloma which develops at the site of injection and that this late antibody production is dependent upon a) stimulation by antigen emerging locally from the globules of water-in-emulsion in the granuloma at the injection site; b) a supply of B cells to this granuloma from the earlier site of anti-HSA biosynthesis, namely the spleen; c) an interference of the normal homeostatic mechanism of antibody production in the local granuloma by mycobacteria. The morphological result is that the germinal centre is prevented from developing in relation to the local granuloma; finally it is proposed that the interference mechanism could be based on the ability of a mycobacterial product to interfere with the ability of dendritic cells to take up anti gen-anti body complexes.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available