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While the source of inflammation in obese subjects is suggested to be mainly the visceral adipose tissue, smoke-induced inflammation originates in the pulmonary system.

Exercise immunology | definition of exercise immunology by Medical dictionary

Here, chronic cigarette smoking induces oxidative stress, resulting in severe cellular damage Exercise and immune system as modulators of intestinal microbiome: implications for the gut-muscle axis hypothesis. Exercise is a possible modulator of intestinal microbiome composition, since some investigations have shown that it is associated with increased biodiversity and representation of taxa with beneficial metabolic functions.

Conversely, training to exhaustion can be associated with dysbiosis of the intestinal microbiome, promoting inflammation and negative metabolic consequences. Gut microbiota can, in turn, influence the pathophysiology of several distant organs, including the skeletal muscle. A gut-muscle axis may in fact regulate muscle protein deposition and muscle function Type 1 diabetes T1D is a T cell mediated autoimmune disease that targets and destroys insulin-secreting pancreatic beta cells.

Beta cell specific T cells are highly differentiated and show evidence of previous antigen exposure. We aimed to explore exercise-induced T cell mobilisation in T1D. In this study, we compared the effects of a single bout of vigorous intensity exercise on T cell mobilisation in T1D and control participants Neuroimmunological and neuroenergetic aspects in exercise-induced fatigue. Feelings of fatigue not only occur in chronic and acute disease states, but also during prolonged strenuous exercise as a symptom of exhaustion.

The underlying mechanisms of fatigue in diseases seem to rely on neuroinflammatory pathways. These pathways are interesting to understand exerciseinduced fatigue regarding immune system to brain signaling and effects of cerebral cytokines. Activation of the immune system incurs a high-energy cost, also in the brain. In consequence immune cells have high energetic priority over other tissues, such as neurons Hallmarks of improved immunological responses in the vaccination of more physically active elderly females.

Physical inactivity is one of the leading contributors to worldwide morbidity and mortality. The elderly are particularly susceptible since the features of physical inactivity overlap with the outcomes of natural aging - including the propensity to develop cardiovascular diseases, cancer, diabetes mellitus, sarcopenia and cognitive impairment. The age-dependent loss of immune function, or immunosenescence, refers to the progressive depletion of primary immune resources and is linked to the development of many of these conditions Microparticles and Exercise in Clinical Populations.

Microparticles MPs are shed membrane vesicles released from a variety of cell types in response to cellular activation or apoptosis. They are elevated in a wide variety of disease states and have been previously measured to assess both disease activity and severity. However, recent research suggests that they also possess bioeffector functions, including but not limited to promoting coagulation and thrombosis, inducing endothelial dysfunction, increasing pro-inflammatory cytokine release and driving angiogenesis, thereby increasing cardiovascular risk Aerobic exercise inhibits acute lung injury: from mouse to human evidence Exercise reduced lung injury markers in mouse and in cells.

Acute respiratory distress syndrome ARDS is defined as hypoxemic respiratory failure with intense pulmonary inflammation, involving hyperactivation of endothelial cells and neutrophils. Toll like receptor expression induced by exercise in obesity and metabolic syndrome: A systematic review. Exercise may act as an anti-inflammatory modulator, but there is no consensus about the role of the TLR in this tuning. The present styudy aims to systematically review the current evidence on exercise-induced TLR regulation in animals and humans suffering from obesity and metabolic syndrome.

Exercise reduces the risk of breast cancer development and improves survival in breast cancer patients. However, the underlying mechanisms of this protective effect remain to be fully elucidated. It is unclear whether exercise can attenuate or modify the pro-tumour effects of obesity and related conditions, such as hyperlipidaemia. This review summarises how hyperlipidaemia and exercise contribute to or reduce breast cancer risk and progression, respectively, and highlights the possible mechanisms behind each Effects of lifelong training on senescence and mobilization of T lymphocytes in response to acute exercise.

However, it has been suggested that chronic exercise may delay immunosenescence. Master athletes represent an interesting sub-demographic group to test this theory since they maintain a high training frequency and load throughout life. The purpose of this study was to evaluate the effects of lifelong training on the senescence and mobilization of T lymphocytes in response to acute exercise. Anxiety and perceived psychological stress play an important role in the immune response after exercise.

There are common pathways by which psychological stress and exercise stress alter immunity. In the aforementioned study, it was found that symptoms of URTI were highest 4 weeks prior to the marathon, and URTI symptoms seemed to re-appear within many of the same athletes 1 or 2 weeks post-marathon.

This study did not confirm the re-emergence of infections by laboratory testing, but if this was indeed demonstrated in future studies, it again shows that acute exercise participation per se does not heighten risk of opportunistic infections. In this case, an underlying infection, not resolved prior to exercise participation, or some other idiosyncrasy, is perhaps to blame.

Such conclusions appear to be supported by evidence from athletes who report the most frequent illness symptoms. For example, these individuals exhibit mostly anti-inflammatory cytokine responses when whole blood, collected at rest, is cultured ex vivo with antigens from diphtheria, tetanus, acellular pertussis, poliomyelitis, and hemophilus influenza type b 68 , A flaw in studies investigating the link between mucosal immunity and purported exercise-induced infection risk is that oral health status is rarely adequately evaluated.

Salivary IgA is heavily involved in host-bacterial ecology and mucosal homeostasis 70 , As optimal oral health is rare in adults—with nearly all exhibiting caries, gingivitis or periodontitis—profound between-person IgA variation has been reported, which is dependent on oral health status Moreover, periodontal diseases are complex and multifactorial, and as a result, studies report large fluctuations in IgA levels relative to disease status between persons, probably due to the bespoke ecological makeup of different host mucosa In addition, oral disease is a common problem in athlete populations 72 , which is likely to be caused by high volume and frequent carbohydrate consumption, and in some, a neglect of oral hygiene, perhaps due to practical constraints.

Thus, changes to oral inflammatory status has not been adequately considered, and emerging salivary biomarkers of oral inflammation, such as immunoglobulin-free light chains 73 , may offer a means of controlling for this confounder. As highlighted elsewhere 70 , salivary IgA is also highly vulnerable to short-term variation, in particular, due to circadian rhythms, typically peaking in the morning, and falling thereafter As salivary IgA secretion is controlled by the parasympathetic and sympathetic nervous system, psychological stress also plays a powerful role in regulating IgA levels Animal models suggest that salivary IgA levels could vary up to fold within the same host over a short period of time Salivary IgA levels are also affected by factors such as sex differences 77 , diet, ethnicity, disease, medications, tobacco, and phase of the menstrual cycle, as reviewed elsewhere To overcome some of these variations in salivary IgA, it is often the case that studies evaluate only secretory IgA sIgA; i.

While this approach may reduce some confounding error, most IgA in saliva contains the secretory component and is, itself, subject to large variation; extensively reviewed elsewhere Given these many considerations, we propose that longitudinal measurement of salivary IgA, as an isolated measure of immune competency within a single host, and even more so between persons, depicts too confusing a picture, and it is ambitious to say that any subtle changes to salivary IgA following exercise reflects immune suppression and a heightened risk of opportunistic infections.

Given the limitations of salivary IgA measurement, research is being undertaken to explore mucosal IgA in other biofluids, and a recent study has shown links between reduced tear IgA levels and infection incidence Others have moved toward more comprehensive oral immunity panels 80 , and such strategies could benefit further from an integrative approach that, in addition to immune parameters, incorporates full dental examination, oral inflammation biomarkers, and host mucosal ecology.

One of the most reproduced findings in human exercise physiology is the profound and transient time-dependent change that arises to the phenotypic composition and functional capacity of lymphocytes in the peripheral bloodstream in response to a single bout of exercise 8. The classic biphasic response of lymphocytes to acute steady state vigorous exercise lasting for around at least 45—60 minutes, is first characterized by a dramatic lymphocytosis. This exercise intensity-dependent mobilization is driven in part by increased shear forces and blood pressure during exercise causing a non-specific flushing of the marginal pools 82 but, moreover, is principally governed by adrenergic stimulation of betaadrenergic receptors on the surface of lymphocytes, arising from adrenaline released during exercise, causing endothelial detachment and subsequent recirculation of lymphocytes into the bloodstream 83 — Upon exercise cessation, the classic biphasic exercise response is next characterized by a dramatic decrease in the frequency of lymphocytes in the bloodstream.

This nadir is typically observed approximately 1—2 h post-exercise when the lymphocyte numerical count is lower than pre-exercise levels; lymphocyte frequency normally returns to pre-exercise levels within 24 h 87 , 89 , Rather than suppressing immune competency however, a more contemporary viewpoint is that this acute and transient lymphopenia 1—2 h after exercise is beneficial to immune surveillance and regulation.

Indeed, in what appears to be a highly specialized and systematic response, it is widely proposed that exercise redeploys immune cells to peripheral tissues e. A seminal study by Kruger and colleagues, using fluorescent cell tracking in rodents, found that T cells are redeployed in large numbers to peripheral tissues including the gut and lungs, and to the bone marrow following exercise 84 , This response has also been proposed to maintain immune homeostasis via augmented regulatory activities Other studies have reported increased lymphocyte apoptosis immediately after exercise i.

While it has not been shown in humans that exercise—in line with rodent models—causes the redistribution of immune cells to peripheral tissues, further support for a coordinated, exercise-induced immune surveillance response elicited by lymphopenia, is revealed by studying the phenotypic characteristics of the cells that preferentially mobilize and subsequently extravasate out of the circulation after exercise. With regard to natural killer cells—the most exercise-responsive lymphocyte subset—CD56 dim cells are preferentially redeployed rather than their CD56 bright counterparts CD56 dim cells are a mature subset of natural killer cells which have exclusive migratory potential for non-lymphoid tissue and potent effector capabilities, including the capacity to produce high amounts of perforin and granzyme, whereas CD56 bright cells are a more immature regulatory cell subset and reside in secondary lymphoid organs, typified by their cell-surface expression of CD62L and CCR7 CD56 dim natural killer cells can be further dissected, into cells with highly potent effector function based on loss of NKG2A and expression of killer immunoglobulin-like receptors and CD57 , In a recent study, it was shown that these natural killer cells, which are capable of rapid effector functions, are preferentially redistributed after exercise , Synergistically, T cells also appear to exert heterogeneous but highly coordinated responses to acute exercise.

Rather than losing or gaining markers of adhesion or activation—as evaluated elsewhere 8 —these changes represent a uniform redeployment of a preferentially mobilized group of memory cells. This response presumably facilitates the detection and elimination of neoplastic, stressed or infected cells in synergy with natural killer cells, as proposed elsewhere Aligned with the immune surveillance theory of Burnet and Thomas, reviewed elsewhere , these results imply that sentinel cells of the immune system are redeployed by exercise-induced perturbations to stress hormones, to exert effector functions against neoplastic, stressed, or infected cells in the hours following exercise.

This process, which occurs daily in a natural diurnal process , orchestrated subtly by stress hormones , , appears to be primed in response to exercise, leading to enhanced immune surveillance However, skin-homing in this context is a role that may be fulfilled by exercise-responsive mucosal-associated invariant T cells ; but further work is needed in this area. A key example illustrating how exercise-induced immune cell redistribution is beneficial to host health can be found in the rapidly emerging field of exercise oncology. Indeed, a recent seminal study demonstrated inhibition of tumor onset and disease progression across a range of tumor models in voluntarily active rodents Importantly, administration of propranolol—a beta 2 adrenergic blocker—abolished the adrenaline-induced redistribution of immune cells, and nullified the anti-tumor effect of exercise on neoplastic growth While these studies are limited to rodents, there is growing evidence that exercise may promote anti-cancer effects in humans.

For example, in a key study recently conducted in humans, it was shown that natural killer cells with a highly mature effector phenotype are preferentially redistributed after exercise, and have the capacity to exert augmented cytotoxicity against myeloma and lymphoma cells in vitro , In light of these results, research is now being conducted to harness the beneficial impact of acute exercise on lymphocyte kinetics for the purposes of cancer immunotherapy Furthermore, in the context of neoplastic growth, this process may be directly responsible for reduced incidence of cancer among physically active people across the lifespan Further comprehensive discussion of the role of exercise and lymphocyte kinetics in anti-tumor responses can be found elsewhere Clearly more research is needed in this area, and a shift in focus toward investigating the benefits—rather than purported detrimental effects—of exercise on health, is no doubt underway and will be a key focus for exercise immunologists in the coming years.

A common misinterpretation, brought about by the exercise-induced reductions to blood lymphocyte frequency in the hours following exercise, is the observation that the functional capacity of immune cells in the peripheral blood is reduced in the hours following vigorous exercise. Thus, during exercise, blood is predominantly occupied by cells capable of responding strongly i. The same principles apply to other cell functions, such as in vitro proliferation in response to mitogenic stimuli.

However, with this measurement in particular, the commonly reported increase in T cell proliferation immediately after acute bouts of exercise is also strongly influenced by laboratory processes and in vitro assay conditions e.


A recent meta-analysis of 24 studies concluded that lymphocyte proliferation is suppressed following acute bouts of exercise, and that a greater magnitude of suppression is caused by exercise lasting longer than 1 h, regardless of exercise intensity However, this meta-analysis did not examine the most important determinant of cell function following exercise: the time-dependent changes in the cellular composition of the samples assayed. Thus, findings such as these should be interpreted with caution if analyses did not differentiate between studies collecting samples immediately after exercise or in the hours following.

As with research focusing on T cells, a similar group of studies citing reductions to natural killer cell cytotoxicity following acute exercise, reviewed elsewhere , did not always take into account dramatic shifts in the constitutional makeup of the natural killer cell compartment, which is known to change in response to exercise Once more, changes to the functional capacity of the total natural killer cell pool are likely to have been misrepresented, given that many of these cells, with potent effector functions, are redistributed to peripheral tissues following exercise cessation.

The principles discussed herein regarding lymphocyte function are also broadly applicable to the assessment of function in other cells, such as neutrophils and monocytes; the response of these cells to exercise is beyond the scope of this article and is reviewed elsewhere 8. We conclude that the results of studies exploring the effects of acute exercise on cell function must be considered very carefully in light of the time-dependent changes in the cellular composition of blood that typically arise following a vigorous bout.

In summary, strong evidence implies that a reduction in the frequency and function of lymphocytes and other immune cells in peripheral blood in the hours following vigorous and prolonged exercise does not reflect immune suppression. Instead, the observed lymphopenia represents a heightened state of immune surveillance and immune regulation driven by a preferential mobilization of cells to peripheral tissues.

As such, nutritional interventions, which have been employed to dampen the magnitude of exercise lymphopenia , are unlikely to reduce the incidence of infections, but interventions that augment exercise-induced lymphocyte trafficking may provide benefits Numerous methods exist to assess the effects of behavioral interventions on immunity but arguably the optimal means of evaluating global immune competency at a systems level is via assessment of the immune response to in vivo challenge, ideally with a novel and clinically recognized pathogen, for example via vaccination In a research context, the most clinically relevant model to assess in vivo challenge in a controlled manner is via vaccination.

Vaccine administration assesses the integrated capacity of the immune system to recognize and process antigen, leading to antigen neutralization. In a clinical research context, vaccination responses are principally quantified clinically in two ways, either via antibody production from antigen-specific plasma cells or via cytokine responses—typically IFN-gamma production—from T cells stimulated with cognate antigen. Evidence from an array of studies, evaluated recently in a comprehensive review elsewhere 9 , indicates that a single acute bout of exercise appears to enhance immune responses to vaccination in both younger and older individuals.

The majority of studies to date have examined muscle-damaging upper arm resistance exercise performed close to the time of vaccination which is administered shortly after the regimen into exercised muscle. However, other modes of exercise, including acute bouts of whole body aerobic activity, have also been investigated. Six of the eight trials identified in the aforementioned review indicated a statistically significant exercise-induced enhancement of immune responses against constituent antigens contained within the vaccine administered — It is notable that in five of these studies, statistically significant benefits were found where the vaccine strains appeared to have lower immunogenicity 9.

For example, it was shown in a trial of young adults, approximately 20 years of age, receiving either a full- or half-dose Pneumovax a pneumococcal vaccine , that those who exercised at the time of receiving the half-dose vaccine had heightened responses to five of the eleven pneumococcal strains contained in the vaccine, whereas no differences were observed for the other six strains; and no benefits of exercise were observed for the full-dose vaccine As such, given the potential effectiveness of exercise as an adjuvant in situations where vaccine immunogenicity is low, studying the effects of exercise on antibody responses in older adults—whom typically exhibit impaired responses—has received considerable attention.

In one recent study, it was found that antibody responses in women 55—75 years of age, were significantly improved when moderate-intensity aerobic exercise was performed immediately prior to vaccination; however, no beneficial effects were found in men Another trial reported no benefits of a single min bout of moderate-intensity walking exercise on the immune response to influenza and pneumococcal vaccination in women around 47 years of age Finally, a very recent study found no effect of a bout of resistance exercise on antibody responses to influenza vaccination in adults approximately 73 years of age It is possible that a number of factors including immunological aging, biological sex and variations in sex hormone levels, and perhaps latent infections e.

Despite null findings, it is important to point out that few, if any, studies investigating the effects of acute exercise on vaccination responses have reported exercise-induced impairment to immune responses, and rather, these studies report that exercise has no effect, or in some cases a beneficial effect, on the immune response to vaccination in older adults. Data from vaccine studies exploring the effects of regular physical activity or frequent exercise training on the immune response to vaccination provides robust support for the argument that exercise enhances, rather than suppresses immunity.

Indeed, at least eight studies have demonstrated heightened vaccination responses in older adults, typically over 60 years of age, who are physically active — Two weeks after influenza vaccination, it was shown that serum anti-influenza IgG and IgM titers were higher in active versus sedentary adults, and so too were peripheral blood mononuclear cell responses to antigen-specific stimulation In addition, a recent study has shown that men aged 65—85 years, who regularly undertook moderate or vigorous exercise training, exhibited higher antibody responses compared to inactive controls in response to an influenza vaccine Data linking habitual levels of physical activity to enhanced immune competency in humans are supported by evidence from animal studies, and show that the immunological benefits of exercise may be particularly beneficial in enhancing otherwise poor responses in older age A major criticism of vaccine and exercise trials conducted in humans is that many solely focus on the maximal antibody titer following vaccination, and it is not practical to follow-up with investigations into infection incidence as a gauge of protection status following vaccination As such, it is unknown whether differences observed with absolute antibody titers, or the amount of IFN-gamma produced from stimulated T cells, between exercise and control groups, is representative of clinically meaningful benefits in terms of protection from infections.

Three elegant studies in rodents imply that benefits, beyond antibody titer, may be brought about by acute exercise. In one of these studies, it was found that antibody responses to influenza exposure were lower in rodents that exercised around the time of exposure, compared to those that did not exercise, yet, exercised mice were still protected and did not exhibit any signs of infection upon re-exposure to the virus Moreover, in an earlier study by the same authors, it was found that mice undertaking an acute bout of exercise before being expose to influenza exhibited a lower severity of infection and had enhanced viral clearance and lower inflammation in the lungs in the days following Thus, it may be the case that exercise enhances immune responses, beyond those captured using maximal antibody titer as an endpoint.

More recent studies have examined the effects of acute exercise on immune competency using other in vivo models of immune challenge that, in principle, also assess the coordinated efforts of immune system components. These studies have employed contact-sensitivity reactions by topically applying to skin, the dendritic cell and T cell stimulant or attractant diphenylcyclopropenone DPCP , and the non-specific inflammatory stimulant, croton oil , For example, in studies of young adults approximately 20—30 years of age , by applying a primary sensitizing dose of DPCP 20 min after 2 h of moderate-intensity treadmill running, and assessing recall challenge 4 weeks later, it has been concluded that this form of exercise impairs both the induction of T cell immunity and the memory response , Thirty minutes of moderate- or vigorous-intensity running had no effect, and no forms of exercise modulated the non-specific inflammatory challenge in response to croton oil , Although these findings are biologically interesting, the clinical relevance of exercise-induced change is unclear, in part, because the process of DPCP-induced immune modulation is not well defined unlike the immune response to antigen administration by vaccination.

We conclude that there is growing evidence from a powerful array of studies in humans and rodents, indicating that exercise enhances, or at least does not suppress immune responses to in vivo challenge in younger and older individuals. Thus, exercise should be encouraged, particularly for older adults who are at greatest risk of infections and who may obtain the greatest exercise-induced benefits to immune competency; an overview of the impact of aging on the immunological benefits that can be attained from exercise is described next.

Research investigating the effects of exercise on immune function has sought to establish whether the observed benefits, as outlined earlier in young adults, such as exercise-induced immune cell mobilisation, that has been implicated in protection against cancer, is also applicable to older adults. However, in this study, it was also shown that following exercise, the magnitude of T cell proliferation in response to mitogens was smaller in young adults, whereas a similar exercise-induced stimulation of natural killer cell cytotoxicity was observed for both groups , It is beyond the scope of this review to fully critique investigations examining the influence of single exercise bouts on the function of different immune cells, with comparisons made between younger and older individuals across the lifespan; we refer the reader to comprehensive reviews on this topic — Nevertheless, it is important to point out that many studies in this area are difficult to interpret: at the time of their publication, the influence of Cytomegalovirus infection on the magnitude of exercise-induced immune responses was not known and was therefore not considered , Moreover, while the magnitude of change to lymphocyte kinetics is likely to be important for detecting and eliminating viral and bacterial infections and neoplastic cells, this process is complex to study, and comparisons between younger and older people is difficult, partly due to other age-associated changes that influence the physiological response to exercise, such as the decline in fitness e.

Immune competency at rest has been assessed in cross-sectional studies, comparing elderly individuals differentiated by physical activity level or cardiorespiratory fitness, or by examining immune function before and after structured exercise training interventions. For example, it has commonly been reported among the elderly, that the most active participants, compared to those who are least active, show the highest T cell proliferation and cytokine production in response to mitogens — Fewer studies have assessed innate immune competency, but higher natural killer cell cytotoxicity has been consistently shown among the elderly who are active compared to less active age-matched controls — Recent studies have expanded measurements into other innate immune cells such as neutrophils.

For example, a recent cross-sectional study of elderly adults, showed that neutrophils from the 20 most active participants, compared to the 20 least active participants, migrated toward interleukin IL -8 with greater chemotactic accuracy, but there were no differences in chemotactic speed In addition, a recent exercise training study has shown in both young and middle-aged adults, that 10 weeks of moderate-intensity continuous cycling training, or high-intensity interval cycling training, improve neutrophil and monocyte phagocytosis and oxidative burst irrespective of age Improvements in these common measurements of immune competency, however, are not always consistent in longitudinal studies employing exercise training interventions, with around half of studies reporting improvements, and half reporting no change — One reason for this could be because the dramatic effects of Cytomegalovirus on driving immunological aging was not considered by most of these studies, and it is feasible that results would be different when examining individuals who are latently infected compared to those who are seronegative.

Importantly however, no studies report impaired immune competency from increased participation in structured exercise. Altogether, we conclude that despite declines in fitness and immune competency, aging does not appear to negate the immunological benefits that can be attained from exercise, and indeed, frequent participation in exercise across the lifespan may lead to immune benefits, even in older age.

Since the first exercise immunology research in the early s, and the substantial increase in scientific interest from the late s and early s , studies examining interaction between immune function and lifestyle factors such as exercise and physical activity have become common. Moreover, preliminary evidence suggests that physical activity and regular structured exercise may even limit or delay immunological aging. Aging is associated with profound changes to the numerical, phenotypic, and functional capacity of almost all innate and adaptive immune cells, resulting in altered immune responses.

Some innate immune cells exhibit numerical, phenotypic, and functional alterations with aging, whereas others appear to be less affected For example, the numbers and functions of eosinophils, basophils, and mast cells appear to be largely unchanged with aging, or at least, there is not a clear effect of age based on the limited current literature Neutrophil numbers often increase with aging, but these cells exhibit diminished phagocytosis and impaired chemotaxis, although chemokinesis is maintained Natural killer cells increase with aging, driven by an accumulation of cytotoxic CD56 dim cells but a decline in regulatory CD56 bright cells, and overall, cytokine production and cytotoxicity are less on a per cell basis These changes with blood monocytes are thought to be mirrored by tissue-resident macrophages, whereby classically activated M1 cells decline, and alternatively activated M2 cells accumulate However, alterations in tissue-resident cells with advancing age are very likely to be a result of adipose tissue accumulation and dysfunction that also occurs in parallel with aging , Indeed, inflamed adipose tissue attracts macrophages with cell-surface characteristics similar to M2 alternatively activated cells—often assumed to be anti-inflammatory.

However, despite their cell-surface phenotype, these cells are potent producers of inflammatory cytokines in adipose tissue, and likely drive age- and obesity-associated inflammation — It is unknown if other, primarily tissue-resident cells, are affected by adipose tissue dysfunction, but with aging, the number and function of dendritic cells have been reported to decrease in the skin and mucosal membranes There is also an age-associated increase in myeloid-derived suppressor cells—a heterogeneous population of granulocytes, macrophages, and dendritic cells—that may impair aspects of immune function by producing reactive oxygen species and inhibitory cytokines Within the adaptive immune system, there are substantial changes to the numbers, function, and phenotype of T cells with aging.

Natural regulatory T cells increase with aging whereas inducible regulatory T cells decrease, but it is unclear if their function is affected Several robust and accepted hallmarks of immunosenescence have been established, especially within the adaptive immune system. In addition, a cluster of parameters, revealed in longitudinal studies of octogenarians and nonagenarians from an isolated population in Sweden, have been referred to as the immune risk profile — Subsequently, high levels of IL-6, TNF-alpha, and C-reactive protein, have been associated with shorter survival — Overall, it is well established that elderly individuals exhibit impaired immune responses to in vivo challenge with novel antigens , , and these individuals are subsequently thought to be at increased risk of infection.

Indeed, a small number of studies have investigated whether the characteristics of the T cell pool are influenced by an active lifestyle. There is a larger body of evidence in young adults, typically between 18 and 30 years, compared to older adults, hereafter considered as being over 40 years of age due to the characteristics of studies published to date. Indeed, very few studies have considered whether relationships between an active lifestyle and markers of an aging immune system could be influenced by other factors, such as body composition. Three groups were formed sedentary, active, and very active on the basis of objectively assessed habitual physical activity, directly measured cardiorespiratory fitness, and body composition assessed with dual energy X-ray absorptiometry It should be emphasized, that among younger adults in particular, mixed results have been reported when investigating links between an active lifestyle and hallmarks of an aging immune system.

Most investigations have been cross-sectional in design, or have made observations between groups over short periods. Thus, it appears that among younger individuals i. It is possible that these changes are due to reactivation of latent viruses, which could be independent of immune function, and driven by exercise-induced adrenergic activity, oxidative stress and inflammatory cytokines 48 — However, these results might also be explained by fluctuations in cell numbers and cell sub-populations in peripheral blood over time.

Such changes have been interpreted as being linked to exercise training load , , but it is also conceivable that these changes occur due to seasonal variation, as has been shown in non-exercise contexts , Although most studies have examined associations between biomarkers of an aging adaptive immune system in young adults, other studies have made measurements across a broader range of ages. As with work examining relationships between an active lifestyle and hallmarks of an aging adaptive immune system in young and middle-aged adults, similar associations have been shown in an older population of 61 men aged 65—85 years These categories were confirmed with a validated physical activity questionnaire and by measurement of cardiorespiratory fitness.

Another recent study compared adults 55—79 years of age who maintained a high level of cycling throughout life to 75 age-matched inactive controls Cyclists also exhibited higher frequencies of recent thymic emigrants and regulatory B cells, lower Th17 polarization, and in plasma, higher IL-7 and lower IL-6 Despite these findings, suggesting a beneficial effect of leading an active lifestyle on immunosenescence among older adults, there is some inconsistency in the literature.

Most investigations of T cell immunosenescence and lifestyle among healthy elderly adults have had cross-sectional study designs. Longitudinal studies, or randomized and controlled trials of exercise training are lacking and might yield promising results. In summary, evidence shows that the characteristics of the T cell pool appear to be influenced by leading an active lifestyle, determined by exercise training, physical activity level, or cardiorespiratory fitness.

Altogether, findings from recent studies examining relationships between an active lifestyle and the characteristics of the T cell pool—as robust and accepted biomarkers of immunosenescence—support observations from some cross-sectional and longitudinal studies, showing that other measures of immune competency, which typically decline with aging, can be improved with physical activity or regular structured exercise — However, further research is needed in this area that employs precise lifestyle measurements e.

In this hypothesis, it is proposed that memory T cells are frequently mobilized into blood during regular bouts of exercise, followed by an extravasation to peripheral tissues, where these cells are exposed to pro-apoptotic stimuli, such as reactive oxygen species, glucocorticoids, and cytokines 11 , Supporting the mechanisms proposed in this hypothesis, many investigations have shown that memory T cells are mobilized into the circulation during exercise, followed by extravasation out of the bloodstream in the hours following 81 , In addition, studies in mice show that lymphocyte apoptosis occurs post-exercise in tissues thought to be the homing destination of mobilized cells Thus, the concept of exercise directly countering memory T cell accumulation is supported by evidence from human and animal studies.

It is unknown whether triggering apoptosis among expanded clones of memory T cells specific for viruses such as Cytomegalovirus is advantageous. For example, in a transplant setting, Cytomegalovirus disease occurs when T cells fail to provide antiviral control and a robust pro-inflammatory response to Cytomegalovirus has been associated with longer survival in the elderly However, it remains to be determined what proportion of the T cell pool needs to be specific for Cytomegalovirus to limit viral reactivation. Traditionally, it has been considered disadvantageous for such a large proportion of the T cell pool to be specific for one virus.

These interpretations are based upon two assumptions. First, there is an upper limit to the size of the immune system, and second, thymic output is negligible after adolescence This concept of a fixed amount of immunological space has since been debated , and thymic output is now known to persist, albeit reduced, up until around 70 years of age Despite uncertainties over the susceptibility of memory T cells to undergo apoptosis, or whether it is advantageous to stimulate their removal, it seems that exercise-induced immune cell death in the tissues has relevance to other processes.

A physically active lifestyle might also counter T cell immunosenescence indirectly, perhaps by limiting adipose tissue accumulation and dysfunction that occurs with aging and obesity , , Indeed, obesity has been linked with impaired lymphocyte proliferation , shorter leukocyte telomere length , and a skewing of the T cell pool toward a regulatory and Th2-phenotype It is generally accepted that repeated stimulation with antigens from Cytomegalovirus drives immunosenescence , , , With obesity, adipose tissue is the primary source of pro-inflammatory cytokines and reactive oxygen species , which can reactivate Cytomegalovirus directly 48 , Thus, exercise might limit T cell immunosenescence by decreasing visceral and subcutaneous adipose tissue , providing a potent anti-inflammatory and anti-oxidative stimulus , In turn, lower systemic inflammation and better redox balance might limit viral reactivation, reducing stimulation with antigens from viruses such as Cytomegalovirus.

In addition, T cell dysfunction might also be prevented, in part, by limiting reactive oxygen species production In summary, leading a physically active lifestyle appears to limit the age-associated changes to the cellular composition of the adaptive immune system, but the mechanisms are yet to be determined.

Exercise might counter the expansion of memory T cells directly, which is desirable assuming these cells contribute to systemic inflammation and not all are required to control latent viruses. However, exercise might affect memory T cell accumulation indirectly, by reducing viral reactivation, or preventing T cell senescence, by controlling adipose tissue deposition and dysfunction that drives inflammation and oxidative stress with aging and obesity. Contemporary evidence from epidemiological studies shows that leading a physically active lifestyle reduces the incidence of communicable e.

However, to this day, research practice, academic teaching, and even physical activity promotion and prescription continues to consider a prevailing myth that exercise can temporarily suppress immune function. We have critically reviewed related evidence, and conclude that regular physical activity and frequent exercise are beneficial, or at the very least, are not detrimental to immunological health.

We summarize that i limited reliable evidence exists to support the claim that exercise suppresses cellular or soluble immune competency, ii exercise per se does not heighten the risk of opportunistic infections, and iii exercise can enhance in vivo immune responses to bacterial, viral, and other antigens.

In addition, we present evidence showing that regular physical activity and frequent exercise might limit or delay immunological aging. We conclude that leading an active lifestyle is likely to be beneficial, rather than detrimental, to immune function, which may have implications for health and disease in older age.

JC and JT contributed equally toward literature searching and retrieval, the ideas and interpretation of the studies described, drafting and revision of the manuscript, and approval of the final version to be published. JT and JC both agreed to be accountable for the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Health benefits of physical activity: a systematic review of current systematic reviews. Curr Opin Cardiol 32 5 — Leisure-time physical activity and the risk of suspected bacterial infections.

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Applying exercise immunology to the field of ecological immunology

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