Stress and Ageing: Effects on Neutrophil Function
The innate or non-specific immune system consists of soluble components, namely the complement system and cellular elements. The latter includes neutrophils, which make up the majority of the innate immune cells in circulation, and deal with rapidly divid
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Stress and Ageing: Effects on Neutrophil Function Anna C. Phillips, Riyad Khanfer and Jane Upton
4.1
Introduction
The innate or non-specific immune system consists of soluble components, namely the complement system and cellular elements. The latter includes neutrophils, which make up the majority of the innate immune cells in circulation, and deal with rapidly dividing bacteria. This chapter will focus on the influence of psychological stress and ageing on neutrophil numbers and function.
4.1.1
Neutrophils
Neutrophils are a major component of innate immunity and are the dominant leukocyte in the circulation, making up 60 % of the white cell count. They are also the shortest lived blood cell, dying by apoptosis approximately 24 h after leaving the bone marrow (Savill et al. 1989; Scheel-Toellner et al. 2004). These cells play a crucial role in killing invading pathogens, particularly rapidly dividing bacteria, and are key cellular components of the early phase of inflammatory responses (Nathan 2006). Neutrophils act quickly and without specificity, although their bacterial recognition systems are many and complex. Neutrophils are recruited to sites of infection via chemical homing (chemotactic) signals, such as the chemokine CXCL8 (also known as IL8). Once in contact with the pathogen they uptake the microbe by engulfing (phagocytosis) mediated via opsonic receptors that detect complement proteins C3b and C3Bi or antibody coating the microbe. Once a pathogen is phagocytosed (Smith 1994), neutrophils have the ability to produce a range of cytotoxic and bactericidal molecules such as reactive oxygen species (ROS) (superoxide production), reactive nitrogen species and proteolytic enzymes from cytoplasmic granules (Nauseef 2007). Superoxide production is a means by which neutrophils eliminate pathogens, and A. C. Phillips () · R. Khanfer · J. Upton School of Sport and Exercise Sciences, University of Birmingham, Birmingham, UK B15 2TT e-mail: [email protected]
J. A. Bosch et al. (eds.), Immunosenescence, DOI 10.1007/978-1-4614-4776-4_4, © Springer Science+Business Media New York 2013
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thus is key in combating infections, by, for example, pneumococcal bacteria (Segal 2005, 2006). More recently a third bactericidal mechanism has been described, namely the externalization of DNA decorated with anti-microbial compounds termed neutrophil extracellular traps (NETs), which mediate extracellular killing of bacteria (Brinkmann et al. 2004). NET generation is also triggered by superoxide generation, though superoxide independent NET generation also occurs. Phagocytosis and generation of superoxide trigger the death of the neutrophil, which is then removed by macrophages leading to the resolution of inflammation (Savill et al. 1989). Their function can be enhanced by pro-inflammatory cytokines, such as granulocytemacrophage colony stimulating factor (GM-CSF), Tumor Necrosis Factor-α (TNFα) and type 1 interferon, which not only amplify their basic bactericidal functions, such as genera
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