Siggins, Matthew Kyle (2012)
Ph.D. thesis, University of Birmingham.
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|
RA0421 Public health. Hygiene. Preventive Medicine
|Institution:||University of Birmingham|
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