| Summary: | This thesis tested the hypothesis that immunosenescence contributes to reduced immunity to \(Streptococcus\) \(pneumoniae\). The effect of age on neutrophil and monocyte responses to \(S.\) \(pneumoniae\) and on CD4+ T cell polarisation during health, pneumococcal carriage and clinical pneumonia infection were determined. Older adult’s neutrophils produced less ROS in response to serotypes 19A and 23F, but not 4, and increased NETs towards 23F. However, neutrophils of older pneumonia patients produced high levels of ROS to all three serotypes but had impaired NET release. Older patients also had immature granulocytes and CD16\(^h\)\(^i\)\(^g\)\(^h\)CD62L\(^d\)\(^i\)\(^m\) neutrophils in blood. CCR2 and CD11b expression, TNF-α and IL-6 production by monocytes were unaffected by age. Pneumococcal colonisation of the nasopharynx is an immunising event. The effect of age on carriage was tested using a human carriage model. Older adults had elevated Th1 and lower Th17 frequencies and failed to generate Th17 memory. During pneumonia, pro-inflammatory subsets increased with age, but Treg frequency and function were maintained. In conclusion, failure of pneumococcal carriage to generate immune memory, together with altered neutrophil responses to \(S.\) \(pneumoniae\) and high frequencies of inflammatory Th subsets in older adults who succumb to infection, could contribute to their increased susceptibility to pneumococcal infection.
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