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Mechanisms of antibody and complement-dependent immunity against nontyphoidal Salmonella in Africa

Siggins, Matthew Kyle (2012)
Ph.D. thesis, University of Birmingham.

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Abstract

Nontyphoidal Salmonella (NTS) are a major cause of fatal bacteremia in Africa. We investigated the role of bactericidal antibody in complement-mediated killing of NTS. Immunised mice serum lacked such activity due to weak complement activity. Mouse anti-Salmonella antibodies were able to effect killing when given a source of human complement. Human serum bactericidal assays showed that the serum-susceptibility of an African clinical isolate varied based on growth conditions. In vitro kinetics of serum-killing, phagocytosis and antibody and complement deposition indicated that a proportion of Salmonellae are phagocytised before serum-killing occurs and this may explain how the protective effects of anti-Salmonella antibodies are undermined in IFN\(\gamma\) deficiency. We studied targets of bactericidal antibodies using an optimised serum-adsorption procedure and a range of different NTS strains and serovars as well as LPS mutants. Antibodies against the immuno-dominant O-antigen (OAg) were a major target of bactericidal antibodies against NTS in human serum. These data support development of an OAg based vaccine against NTS. Finally, using electron microscopy, we showed the physical effects of serum-killing on Salmonellae and also demonstrated that a major difference between inhibitory and bactericidal serum was the quantity of complement deposited on Salmonellae.

Type of Work:Ph.D. thesis.
Supervisor(s):MacLennan, Calman and Cunningham, Adam and Henderson, Ian
School/Faculty:Colleges (2008 onwards) > College of Medical & Dental Sciences
Department:School of Immunity and Infection
Subjects:DT Africa
QR180 Immunology
RA0421 Public health. Hygiene. Preventive Medicine
Institution:University of Birmingham
ID Code:3665
This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder.
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