Use this URL to cite or link to this record in EThOS:
Title: Antibody-mediated protection against Salmonella infections
Author: Goh, Y. S.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2011
Availability of Full Text:
Full text unavailable from EThOS.
Please contact the current institution’s library for further details.
In this project, I examined how antibody targeting different bacterial proteins and how the different antibody subclasses affect the interaction of opsonised bacteria with their host cells, using Salmonella strains expressing a foreign CD52 mimotope either in the flagellin protein, FliC, or in the outer membrane protein, OmpA, that can be recognized by a panel of chimaeric antibodies. Immunofluorescence studies examining the percentage of infected cells and the bacterial load per infected cell, and experiments examining intracellular bacterial viability revealed that the greatest enhancement of phagocytosis and the following antibacterial activity was observed with IgG3 opsonisation, followed by IgG1, IgG4, and IgG2, IgG3 was also more efficient in mediating phagolysosome fusion, followed by IgG1, IgG4, and IgG2, indicated by a higher percentage of bacterial co-localisation with TROv and cathepsin D. In addition, similar studies on cells differentially stimulated to induce different Fcγ receptor profiles have shown that cells expressing higher levels of FcγRI, FcγRIIA and FcγRIII are more efficient in the above mentioned phagocyte functions. Further investigations, using anti-FcγR antibodies to block host Fcγ receptors, revealed that IgG1-, IgG3- and IgG4-mediated phagocyte functions have a higher dependency on FcγRI over FcγRIIA, while IgG2-mediated phagocyte functions have a higher dependency on FcγRIIA over FcγRI. Taken together, the findings suggest that FliC and OmpA could be promising bacterial targets for vaccine development, and the distribution of the different antibody subclasses in the antibody profile might be important in antibody-mediated protection.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available