Copyright EMAP Publishing 2017 This article is not for distribution Nursing Practice Keywords Thymus/Phagocytes/ T cells/B cells/Inflammation Systems of life This article has been Immune system double-blind peer reviewed In this article... l Age-related changes to the innate and adaptive immune responses l Thymic involution and immunosenescence l Decreased production and impaired function of ageing immune cells Anatomy and physiology of ageing 9: the immune system Key points Author Yamni Nigam is associate professor in biomedical science; John Knight is Almost all senior lecturer in biomedical science; both at the College of Human Health and components of Science, Swansea University. the immune system are adversely Abstract With advancing age, the body’s ability to respond to infection declines, affected by age and recovery from injury or microbial attack becomes delayed or ineffective. This is called immunosenescence. The innate immune response, the acquired immune One of the earliest response and the inflammatory response are all blunted, and the immune system and most drastic becomes less able to mount a rapid and complete defence against invading changes in the pathogens. Ageing also means older people respond less well to vaccines and immune system is are more prone to autoimmune conditions. This is the ninth article in an 11-part series thymic involution on the effects of ageing on the systems of the body. The innate immune Citation Nigam Y, Knight J (2017) Anatomy and physiology of ageing 9: the immune response, provided system. Nursing Times [online]; 113: 10, 42-45. by mechanical barriers, and cells with phagocytic urvival depends on the body’s innate defences change profoundly, but and killing abilities, ability to protect itself against the adaptive defences undergo an even is blunted environmental dangers, harmful more severe age-related deterioration. Ssubstances and pathogens. It The weapons of the does this using non-specific, natural Innate immune response adaptive immune (innate) defences such as the skin, secre- The innate immune system has two lines response, T cells and tions, immune cells and chemicals. The of defence: B cells, undergo a innate immune system is bolstered by the l The skin, and the epithelial and decline in numbers inflammatory response (Box 1), which mucosal linings of internal organs; and function increases blood flow to damaged areas and l Non-specific white blood cells encourages phagocytic leucocytes to enter (leucocytes) and secreted molecules, Better vaccines, a injured tissues and engulf pathogens. The including antimicrobial factors such healthy population non-specific immune responses are as defensins, which can pierce the of gut microbes, complemented by acquired (adaptive) membranes of pathogens. vitamin intake, zinc immune responses, which develop more If a pathogen breaches the exterior, supplementation gradually but more robustly, targeting first-line barrier, the second-line internal and exercise can individual pathogens and ridding the body defences come into play. The hallmark of support the ageing of malignant cells. the second line of innate defence is inflam- immune system Almost all components of the immune mation (Box 1). The innate defence also system are adversely affected by ageing, depends heavily on cells that can phago- resulting in an overall decline in immuno- cytise pathogens – neutrophils, mono- competence. The system becomes less able cytes and macrophages. to mount an effective response and the mechanisms normally invoked to get rid Skin, mucous membranes and eye lashes of a foreign agent are disrupted; this The skin contains keratin, a waterproof decline is called immunosenescence. The and microbial-resistant protein. Lactic Nursing Times [online] October 2017 / Vol 113 Issue 10 42 www.nursingtimes.net Copyright EMAP Publishing 2017 This article is not for distribution Nursing Practice Systems of life acid secretions allow the skin to maintain a Box 1. Inflammation and inflammageing slightly acidic environment (pH5.5) and sebaceous and sweat glands produce secre- Inflammation isolates and protects the body from further injury and the spread of tions that can inhibit bacterial growth. invading pathogens. Histamine release causes an increase in blood flow to the injury With age, skin secretions diminish; the site, and prostaglandins allow white blood cells and plasma to migrate out of the skin becomes thinner, drier and less capillaries. A cascade of complement proteins in the plasma kick-starts this elastic, and therefore more prone to cuts physiological process, which results in the classical symptoms of inflammation: and abrasions through which pathogens redness, heat, swelling and pain. can enter the body. Medical devices such as With age, in the presence of infection, both the complement pathway and the intravenous cannulas provide skin activation of inflammation are reduced (Navaratnarajah and Jackson, 2017). Ageing breaches, so should only be used when is also associated with a long-term, continuous state of low-grade inflammation absolutely necessary, removed as soon as (inflammageing), which can trigger other pathological mechanisms. This low-grade possible, and accompanied by tight infec- systemic inflammation is considered the primary risk factor for major long-term tion prevention and control measures. conditions in older people (Isobe et al, 2017). Mucous membranes line cavities, tracts and structures throughout the body. The mechanical protection provided by their mediators, including cytokines and immune response usually kicks in a few tough epithelium is reinforced by the pro- chemokines, playing a key role in the days after the innate immune response. duction of mucus that traps particulate inflammatory process (Box 1). When they matter and pathogens. With advancing encounter invading microbes, they initiate The thymus age, the integrity of the epithelial barrier inflammation – recruiting and activating Precursors of B and T cells are formed in and mucosal immune response are com- other phagocytes. Macrophages are also the bone marrow, but T cells mature into promised (Man et al, 2014). key to wound healing, producing growth immunocompetent lymphocytes in the Eyelashes keep debris out of eyes; like factors and secreting angiogenic and fibro- thymus gland. Located just above the hair, they grow through specialised folli- genic factors. With age, there is a sharp heart, this lymphoid organ is large and cles, but this process slows down with age, decline in the function of macrophages, active in early childhood and then rapidly and eyelashes become thinner. and their phagocytic, killing and wound- decreases in size, at a constant rate, until healing capacities are reduced (Linehan middle age. Atrophy (shrinking) of the Cells of the innate immune system and Fitzgerald, 2015; Solana et al, 2012). thymus is one of the earliest and most Neutrophils drastic changes in the immune system and The primary immune defence against rap- Dendritic cells this is thought to play a major role in idly proliferating bacteria, yeast and fungi Dendritic cells are antigen-presenting leu- immunosenescence. It results in a gradual are phagocytic neutrophils, which can kocytes found at the body’s frontiers such decrease in the output of naive T cells, destroy pathogens by rapid generation of as skin. They activate T-lymphocytes and which essentially stops between 50 and 60 potent reactive oxygen and nitrogen spe- play a pivotal role in the adaptive immune years of age (Muller and Pawelec, 2015). cies, as well as extrude neutrophil extracel- response (see below). The production of various immunoregula- lular traps. Neutrophils are also important tory hormones that differentiate T and B in wound healing: they arrive at the wound Natural killer cells cells also decreases: some are no longer site within minutes of an injury and con- Natural killer cells (NKCs) are non-specific detectable in the plasma of people over 60. tinue to do so for several days. cytotoxic white blood cells involved in early One role of the thymus is to mature T With advancing age, the number of defence. Known as the pitbulls of the cells that have not yet been exposed to anti- neutrophils remains constant but their immune system, they recognise and elimi- gens. These ‘naive’ T cells are quiescent, function is affected (Solana et al, 2012); nate a variety of virus-infected cells and and will only become active when exposed reduced phagocytosis (ability to ingest malignant cells by direct contact. Their to a foreign antigen. Another role of the microbes) may lead to an accumulation of ability to kill is seen as a biomarker of thymus is to ‘educate’ T cells to recognise debris, while reduced chemotaxis (move- healthy ageing, and low NKC activity is self-antigens, so that they do not mount an ment in response to chemical stimulation) associated with the development of diseases attack against self-cells and tissue. Here, means neutrophils take longer to reach the and infections. Absolute numbers of NKCs maturing T cells are checked to ensure that site of infection. Neutrophils secrete pro- increase with age but their cytotoxic abili- they do not strongly respond to self body teases to aid their migration through tis- ties decrease (Shaw et al, 2010). Age-associ- proteins. Due to thymic atrophy, this sues: this also becomes less efficient with ated alterations in NKC function may result ‘thymic education’ is impaired by ageing, age. Tissue damage and inflammation are in part from changes in zinc homoeostasis; which may partly explain why we have therefore more frequent and more severe there is some evidence zinc supplements more autoantibodies as we age. in older people (Shaw et al, 2010). improve NKC function (Mariani et al, 2008). T cells Monocytes and macrophages Adaptive immune response Matured naive T cells are exported to the Monocytes are white blood cells located in The main weapons of the adaptive immune secondary lymph organs (lymph nodes the spleen and blood. They respond to system are B and T cells (lymphocytes), and spleen), where they are more likely to inflammation by differentiating into which create and acquire immunity to spe- encounter foreign antigens.