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Ageing is accompanied by impairments in immune responses. In this thesis, an age associated numerical and functional deficit in a novel subset of immunosuppressive CD19\(^+\)\(^v\)\(^e\) CD24\(^h\)\(^i\) CD38\(^h\)\(^i\) B cells is reported which might be an additional factor contributing towards increased risk of systemic autoimmunity with advancing age. The immune system is profoundly affected by environmental factors such as stress. This thesis also examined the synergistic effect of the physical stress of a hip fracture and the psychological stress of depressive symptoms on immune function of older adults. It was observed that 37% of our hip fracture patients had developed depressive symptoms 6 weeks post-surgery. A significant decline in neutrophil, monocyte and NK cell functioning was reported in hip fracture patients with depressive symptoms, but not in those with hip fracture alone. Additionally, an increased cortisol: DHEAS ratio was also only found in hip fracture patients with depressive symptoms. An elevated level of pro-inflammatory (IL6, TNFα) and anti-inflammatory (IL10) cytokines were observed in hip fracture patients with depressive symptoms. In the adaptive immune system, a reduction in circulating T cells and an accumulation of senescent and activated T cells was also found in the hip fracture patients who developed depressive symptoms. Finally, the age associated numerical and functional deficit in IL10 production by CD19\(^+\)\(^v\)\(^e\) CD24\(^h\)\(^i\) CD38\(^h\)\(^i\) B cells was further suppressed on exposure to chronic stress in hip fracture patients with depressive symptoms. |
