The Immune System in the Elderly: A Fair Fight Against Diseases?

Anis Larbi; Paulina Rymkiewicz; Anusha Vasudev; Ivy Low; Nurhidaya Binte Shadan; Seri Mustafah; Shamini Ayyadhury; Tamas Fulop

Disclosures

Aging Health. 2013;9(1):35-47. 

In This Article

Innate Immunity in Aging

Immunosenescence is also characterized by changes in the innate immune system. The innate immune system is the first line of defense and is important for early defense against pathogens. With age, cells of the innate system, notably neutrophils, monocytes/macrophages and dendritic cells, undergo changes that lead to compromised functioning of the immune system. With aging, monocytes have been shown to increase in numbers.[9] Defective Toll-like receptor (TLR) function has also been studied in monocytes, where the production of cytokines IL-6 and TNF-α have been shown to be reduced when induced by TLR1/2.[10] Age also has a general suppressive effect on dendritic cell function. With aging, neutrophils display reduced functions, for example, slowed response to chemotaxis, phagocytosis, generation of superoxide, alterations in signal transduction and membrane lipid rafts.[11] The study by Lord et al. demonstrated that the age-related decline in neutrophil functions is in part explained by the reduced Fc-γ receptor expression.[12] The response to CD16 triggering, as well as to granulocyte–macrophage colony-stimulating factor and N-formyl-methionine–leucine–phenylalanine stimulation, is reduced, suggesting that even when receptor expression is maintained, as it is for granulocyte–macrophage colony-stimulating factor receptor, the signaling cascade leading to activation is impaired. Animal studies also confirmed the hypothesis that proximal events of the receptor may explain the reduced activation level of the cells following stimulation.[13] Some events associated with signaling and activation may also interfere with neutrophil functions. For instance, as dehydroepiandrosterone sulfate levels are highly reduced with aging (adrenopause), this could greatly impact neutrophil activation. Lord et al. have shown that dehydroepiandrosterone sulfate increases superoxide generation of neutrophils via a PKC-β/p47(phox) pathway.[14] This suggests that antibactericidal activity may be altered due to extrinsic reasons and that modulation of neutrophil activity is possible.

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