Wilson, RJ;
(2014)
Natural adaptive immunity to Streptococcus pneumoniae lung infection.
Doctoral thesis (PhD), UCL (University College London).
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Abstract
Streptococcus pneumoniae is an important respiratory pathogen and a leading cause of community-acquired pneumonia. As well as invasive disease S. pneumoniae also colonises the nasopharynx. Colonisation with S. pneumoniae is nearly universal in infants, dropping to 10% in adulthood. This frequent exposure has potential for developing and boosting natural adaptive immune responses. However naturally-acquired immune responses that protect against subsequent lung infection with S. pneumoniae are not fully understood. This thesis investigates the targets and function of naturally-acquired IgG to S. pneumoniae in humans and additionally the mechanisms of protection from lung infection following experimental colonisation in mice. The target and function of naturally-acquired IgG in human sera and pooled intravenous immunoglobulin (IVIG) preparations was assessed. IVIG, pooled from >1000 adult donors provides a tool to investigate the natural antibody responses to S. pneumoniae within a population. Data indicate that naturally-acquired human IgG predominantly binds to non-capsular antigens on the surface of S. pneumoniae and can target surface exposed protein antigens. In vitro assays indicate that antibodies to non-capsular targets may be functional, enhancing phagocytosis and killing of S. pneumoniae. In vivo human IgG protected against lung infection. Cellular depletion demonstrated that protection within the lung required neutrophils and clearance of S. pneumoniae from the blood required macrophages. A model of lung infection in the absence of bacteraemia using S. pneumoniae strain EF3030 was developed. This model allowed assessment of the immune responses to S. pneumoniae colonisation of the nasopharynx that protect against re-infection specifically within the lung. Prior nasal colonisation with S. pneumoniae EF3030 was protective against subsequent lung infection. Cellular depletion strategies and challenge in antibody-deficient mice demonstrated that protection against lung infection required the development of both humoral and cell-mediated immunity.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | PhD |
| Title: | Natural adaptive immunity to Streptococcus pneumoniae lung infection |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Keywords: | S. pneumoniae, Lung infection, Respiratory infection |
| UCL classification: | UCL > Provost and Vice Provost Offices UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1417184 |
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