Pages: 23

The study of exercise and immune function has been ongoing since the 19th century. In its early beginnings, the main focus of research was on the measurement of blood leukocytes and infection susceptibility. The study of exercise immunology expanded greatly towards the end of the 20th century, upon the arrival of technical advances in mainstream immunology and because of wider interest in the health benefits of exercise. Now, in the 21st century, exercise immunology is principally focused on how exercise can be harnessed to prevent and treat diseases. Whilst it is not possible to capture every important discovery, the purpose of this chapter is to provide a synopsis of some of the major developments in the field of exercise immunology.

Pages: 24

The human body is frequently exposed to harmful challenges, both from external sources (such as viruses, bacteria, fungi, and parasites, also called pathogens) and internal sources (such as tumours). The immune system provides several layers of defence to protect against these challenges, and when successful, a state of immunity is established (Latin: immunitas, freedom from). However, the robustness and regulation of this response are influenced by many factors, including exercise, as outlined in the remaining chapters of this book. The present chapter provides a concise overview of the human immune system components that are most relevant to exercise immunology. The focus will be on the characteristics and functions of different cells of the immune system and other soluble components that contribute to the mechanisms giving rise to a whole-body immune response.

Pages: 28

Standardised and validated methods are key components to evaluate the impact of exercise on the immune system. This chapter will introduce the most commonly used methods in the field of exercise immunology centred around three sections. First, different methods for inducing the so-called “stress-induced immune response” are presented, and the importance of both physical and psychological stressors are outlined. Second, methods for the sampling of biological material are summarised. Third, laboratory methods – also referred to as “assays” – that are commonly used to assess aspects of immunity in exercise immunology are introduced, including assays for measuring cells and soluble components of the immune system. The primary focus of this chapter is human methodology, but animal models are briefly summarised when appropriate. The strengths and drawbacks of most methods are highlighted, and readers are directed to in-depth resources and validated laboratory protocols for more details. Finally, the chapter provides key considerations regarding general methodology such as the use of controls and reference samples.

Pages: 27

This chapter describes the effects of individual bouts of exercise and longer-term exercise training on the number, proportions, and functions of leukocytes and leukocyte sub-types in blood. Compared with other forms of exercise, prolonged vigorous endurance exercise causes the largest changes to leukocytes. Innate immune cells, primarily neutrophils, and natural killer (NK) cells, exhibit the largest responses to exercise. Neutrophil numbers increase almost immediately during exercise and remain elevated for several hours after exercise cessation. Most lymphocyte sub-types also increase almost immediately during exercise, but many of these cells fall below pre-exercise values 1–2 hours after exercise cessation, sometimes remaining at this level for several hours or even days. The magnitude and pattern of this biphasic response differs between lymphocyte sub-types – with the strongest responses exhibited by NK cells and T cells, in particular effector-memory T cells. Exercise-induced changes to cell function are best described for NK cells and T cells, with many articles from the 1980s to the 1990s reporting a decline function 1–2 hours after exercise, which was once thought to represent immunosuppression. It is now generally agreed that these findings are largely caused by a lower proportion of effector cells in blood post-exercise because they migrate to tissues as part of immune surveillance. In contrast to the short-term effects of individual exercise bouts, knowledge on long-term adaptations to exercise training is less conclusive. Some evidence suggests that exercise training causes changes to the numbers and proportions of some cell types, but further research is required to confirm these effects and to understand mechanisms.

Pages: 30

This chapter will introduce the effects of both individual bouts of exercise and regular exercise on a wide array of soluble factors secreted into biofluids such as blood (plasma or serum) and mucosal or respiratory tract fluids (e.g. saliva, sputum, tear fluid, mucosal lining fluid lavage). The field of exercise immunology has investigated the effects of exercise on immunoglobulins, complement, cytokines, antimicrobial peptides, and acute-phase proteins. This chapter reflects the state of the art of knowledge on soluble factors in the context of immune competency and inflammation at mucosal surfaces and in the circulation.

Pages: 26

The immune system interacts with every tissue and organ in the body. These interactions play essential roles in health and disease, and the significance of these tissue–immune interactions in the body’s response to exercise has emerged as an exciting area of investigation. This chapter will explore the immune system’s role in adipose tissue, skeletal muscle, and gut microbiome health, as well as its function as a mediator of the beneficial effects of exercise in these tissues. Individual exercise bouts and exercise training affect tissue-resident immune cells within adipose tissue and skeletal muscle. In addition, these immune cells appear to mediate some of the beneficial effects of exercise on these tissues, promoting tissue remodeling, regeneration, and repair. Cytokines, adipokines, myokines, and extracellular vesicles from immune cells, adipocytes, and myocytes facilitate crosstalk between tissues and the immune system. This crosstalk is not only important for tissue health and homeostasis, but it also guides the coordinated response to exercise. The effects of exercise on the gut microbiome and the community’s complex, dynamic interaction with the immune system is also an emerging area of research with interactions between exercise, the gut microbiome, and the gastrointestinal immune system having critical systemic implications.

Pages: 22

This chapter summarises research which has used a variety of methods to understand the impact of exercise on immune function, with a specific focus on how exercise affects the competency of the immune response to pathogenic challenge. Prior chapters have described how exercise affects the cellular (Chapter 4) and soluble (Chapter 5) basis of the immune system. Later chapters will outline the links between exercise and numerous health outcomes, including infection susceptibility (Chapter 9). This chapter bridges those early chapters with later chapters in this book, by summarising key studies that have investigated how exercise affects the functional competency of the immune system in vivo (i.e., in a living organism, such as a human or an animal). Different approaches exist to understand how exercise affects immune competency in vivo, and studies summarised in this chapter have principally used models such as wound healing or methods of immune challenge including vaccination or infection. This chapter will summarise findings from key studies in this research area. Whilst this chapter focuses predominantly on translational endeavours in the setting of infection susceptibility, many of the studies summarised here reach beyond this context and provide meaningful insight into understanding the impact of exercise on non-communicable diseases (Chapters 10–12).

Pages: 26

Advancing age is associated with an increased risk for chronic disease, opportunistic infections, and mortality – driven by a remodelling and decline in immune function, termed immunosenescence. Although chronological ageing and exposure to some infections are considered driving forces behind immunosenescence, it is now recognised that certain lifestyle factors including sedentary behaviour not only accelerate the onset of immunosenecence but also exacerbate many of its hallmark features. This chapter begins by introducing the impact that ageing has on various components of the immune system, including cellular, soluble, and systemic functions. Next, this chapter provides an overview of the effects of both individual bouts of exercise and regular exercise training on immunity in older adults. Finally, this chapter concludes with an up-to-date review of the available evidence linking exercise with improved immunity in older adults.

Pages: 20

This chapter reviews the current understanding of the effects of moderate exercise and heavy exercise on immunity and infection risk in non-athletes and in athletes. In particular, the risks for symptoms of acute respiratory infection following individual exercise bouts or following periods of exercise training are considered, as are changes in possible mechanisms including salivary immunoglobulins and blood leukocytes. The potential contribution of non-exercise factors to infection risk in athletes is also discussed. Immune differences between elite athletes and the general population are reviewed. This chapter concludes with a brief consideration of exercise in the context of novel, emerging pathogens.

Pages: 29

This chapter aims to enhance the reader’s understanding of the role of exercise and physical activity on the immune system of people with cancer. It is well established that physical activity and exercise protect against cancer development. The risk of developing cancer is further lowered when physical activity and exercise participation are higher in a dose-response relationship. A growing body of work suggests that exposure to exercise following a cancer diagnosis may lower cancer progression, reduce side effects, and potentially reduce mortality. Physical activity and exercise training have potent immune-enhancing effects in the general population. Therefore, it is likely that the immune system mediates some of the benefits of exercise in patients with cancer. This chapter will explore the putative effects of exercise on reprogramming or maintaining the functions of the immune system before, during, and after a cancer diagnosis. We provide a brief overview of how the immune system responds to cancer. Then, we will outline how exercise affects the immune system to potentially prevent breast and colorectal cancers. We will then explore the impact of exercise on people with solid or haematologic cancers, focusing on the cellular and soluble responses. Following this, we will discuss the impact of exercise on people who have completed cancer therapies and can be classified as cancer survivors. Finally, a summary of these observations, future directions, and potential key mechanisms is provided.

Pages: 28

Autoimmune disorders comprise a heterogeneous group of diseases that develop following a loss of immune self-tolerance resulting in immune-mediated organ dysfunction and chronic inflammation. Common autoimmune disorders include type 1 diabetes, rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, spondyloarthritis, and myositis. In addition to pharmacologic agents as treatment for autoimmune disorders, exercise, and physical activity are now recommended as therapy for the general clinical care of patients with these diseases. Exercise training benefits patients with autoimmune disorders in multiple ways, including improving (1) general health: physical function, quality of life, pain, and cardiometabolic disease risk; and (2) disease-specific features: inflammation and disease activity. This chapter summarizes current knowledge regarding exercise in the management of individual autoimmune disorders. Discussion in this chapter on exercise immunology in autoimmune disorders also highlights current gaps in knowledge for the field, including the physiologic responses to individual bouts of exercise, effects of exercise on immune function, and pathways in which exercise imparts benefits for these patients.

Pages: 19

The human immune system is implicated in the development and progression of cardiometabolic diseases (including cardiovascular disease, type 2 diabetes, and metabolic syndrome). This is typified by altered numbers, phenotypes, and functions of innate and adaptive immune cells, exhibiting a pro-inflammatory phenotype. These pro-inflammatory cells contribute to the aetiology and pathology of cardiometabolic disease through invasion of the vascular wall in atherosclerotic disease (cardiovascular disease) and infiltration into adipose tissue, exacerbating adipose-mediated inflammation (for example, in type 2 diabetes). Regular exercise has many benefits for those with cardiometabolic disease, but whether these effects are mediated by alterations in immunity are unknown. The current evidence suggests that regular exercise, independent of modality (endurance, resistance), can curb monocyte/macrophage inflammatory indices, as well as positively affect lymphocyte phenotypes in both animal and human models. This chapter discusses the involvement of the immune system in cardiometabolic disease, providing key mechanisms, plus evidence concerning the role of regular exercise participation to affect the immune system, and subsequent impact on disease parameters.

Pages: 20

Individuals in a wide variety of exercise and occupational settings can be exposed to various environmental stresses, including heat and humidity, cold conditions, altitude hypoxia, weightlessness, and air pollution. Many field-based studies show that exercise, in combination with these environmental stressors, has a profound impact on a range of cellular and soluble immune measures. Researchers have also proposed several regulatory models to explain mechanisms and mediators dictating how exercise in conjunction with environmental stress affects the immune system. A range of countermeasures to preserve immune function in these settings have evolved including acclimation strategies, therapeutic and dietary interventions, and individualised exercise programmes. Evaluation of relevant research reveals strengths and weaknesses of laboratory, field and clinical research, and identifies selected practical recommendations for individuals, practitioners, and researchers. Emerging diagnostic technologies will permit next-generation evaluation of immune function in sporting, clinical, practical, and research settings.

Pages: 23

The relevance of nutrition in exercise immunology can be divided broadly into two main areas. First, and traditionally, exercise immunology studies have examined whether broad nutritional interventions and supplementation with specific macronutrients or micronutrients, influence overall immune function – including susceptibility to upper respiratory tract infections – and aspects of soluble or cell-mediated immunity, both at rest and in response to exercise. Second, more recent studies have examined the role of nutrients and cellular metabolism (immunometabolism) in the regulation of immune-cell function. This chapter begins with an overview of traditional research in exercise immunology, including the influence of energy intake, macronutrients, micronutrients on infection susceptibility, and immune responses to exercise. However, this chapter does not focus on this topic, and instead readers are directed toward comprehensive reviews which also include practical nutrition recommendations for athletes. The main focus of this chapter is the effects of nutrition on cellular metabolism and metabolic reprogramming, which have become highly significant to the study of immunity in the past two decades, with relevance to aging and chronic disease. Indeed, this chapter describes the metabolic pathways regulating immune-cell function, as well as how these pathways are altered by nutrition and how they can become dysregulated in disease states. Finally, this chapter provides a brief overview of the limited known effects of exercise on immunometabolism.

Pages: 21

Psychological stress is a potent modulator of immune function. Acute short-term psychological stress leads to transient increases in the number and functions of circulating immune cells, enhancing protection against pathogenic threats. Conversely, exposure to excessive and sustained psychological stressors is associated with impaired immunity and increased risk of infections. A physically active lifestyle contributes to mental and physical wellness. The positive health benefits of regular moderate-intensity exercise training on cardiovascular health, metabolic function, and immunity are irrefutable. Less well-understood, however, is how regular exercise positively impacts the immune system, and how exercise and physical activity modulate the immune response to psychological stress. This chapter will present evidence supporting the concept that regular exercise and physical activity protect immune function from so-called immune-disruptive challenges, such as excessive and chronic stress, by modulating a stress-reactive neural circuitry and relevant immune outcomes associated with improved health.