The first-line effector mechanisms of immune defence, including inflammation and oxidative burst, contribute significantly to host-pathogen resistance. Whether these immune responses undergo age-related changes in birds remains unknown. Here, we tracked selected inflammatory parameters in 54 free-living great tits (Parus major) of known age, captured repeatedly over three consecutive years, with the aims to investigate long-term repeatability and age-dependent changes in cellular oxidative burst responsiveness upon in vitro stimulation with bacterial lipopolysaccharide (LPS), and to identify its relationships with leukotriene B4 (LTB4) levels and haematological traits. In addition, we linked these immunological traits to selected physiological markers (antioxidants and oxidative stress markers). LTB4 levels increased with age and we have shown a similar non-significant tendency also for absolute granulocyte counts, indicating propagating chronic inflammation over the bird's lifetime, consistent with the inflammaging hypothesis. In contrast, cellular oxidative burst followed a quadratic trend of dependency on age with a peak in midlife individuals, in line with the immunosenescence hypothesis. Interestingly, LTB4 levels were positively associated with general oxidative damage, but negatively with antioxidant glutathione peroxidase activity, indicating links to redox balance. This longitudinal study demonstrates the contrasting patterns of age-related changes in background and acute markers of pro-inflammatory immunity contributing to immunosenescence in birds and thus provides basis for interpretation of the tested inflammatory markers in cross-cohort datasets.

• Klíčová slova
• Ageing, Aging, Avian inflammaging, Birds, Ecoimmunology, Haematology, Immunosenescence, Inflammation, Innate immunity senescence, Oxidative burst, Oxidative damage, Oxidative stress, Passerines, Redox balance, Respiratory burst, Testosterone, Wild,
• MeSH
• imunosenescence * MeSH
• lidé MeSH
• longitudinální studie MeSH
• oxidační stres MeSH
• stárnutí MeSH
• zánět MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Aging is associated with progressive loss of physiological integrity, leading to impaired physical and mental functions as well as increased morbidity and mortality. With advancing age, the immune system is no longer able to adequately control autoimmunity, infections, or cancer. The abilities of the elderly to slow down undesirable effects of aging may depend on the genetic background, lifestyle, geographic region, and other presently unknown factors. Although most aspects of the immunity are constantly declining in relation to age, some features are retained, while e.g. the ability to produce high levels of cytokines, response to pathogens by increased inflammation, and imbalanced proteolytic activity are found in the elderly, and might eventually cause harm. In this context, it is important to differentiate between the effect of immunosenescence that is contributing to this decline and adaptations of the immune system that can be quickly reversed if necessary.

• MeSH
• cytokiny metabolismus   MeSH
• imunitní systém fyziologie   MeSH
• imunosenescence * MeSH
• lidé MeSH
• lymfocyty cytologie   MeSH
• zánět patologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• cytokiny MeSH

Neuroblastoma survivors show signs of immunosenescence early after therapy in CD8+ T cell compartment and elevated plasma TNF-α but in later follow-up immune recovery comes into play. Whether the recovery phenotype is long lasting or transient remains to be elucidated, however, late adverse effects often occur in childhood cancer survivors.

• Klíčová slova
• adverse late effects, childhood, immune recovery, immunosenescence, neuroblastoma,
• MeSH
• CD8-pozitivní T-lymfocyty imunologie   MeSH
• imunosenescence imunologie   MeSH
• lidé MeSH
• neuroblastom imunologie   MeSH
• přežívající onkologičtí pacienti MeSH
• přežívající MeSH
• rizikové faktory MeSH
• TNF-alfa imunologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• dopisy MeSH
• práce podpořená grantem MeSH
• Názvy látek
• TNF-alfa MeSH

Immunosenescence is characterized by remodeling and dysregulation of immune system due to aging process. These changes affect innate as well as adaptive immunity. Due to the complexity of the physiological processes, in which the mechanisms of the immune system interfere, also other systems of the organism are affected by these changes. Thymus involution as well as chronic antigenic stimulation are the main causes of immunosenescence and lead to a proinflammatory setting of the organism. In addition to impaired immune response against infections or reactivation of latent infections, reduced response to vaccination or decreased antitumor immune surveillance, changes of the immune system in elderly are clinically reflected in the development of chronic diseases typical for older age groups, such as neurodegenerative or metabolic diseases. The mechanisms of immunosenescence can be at least partially influenced by an active lifestyle and adequate dietary measures.

• Klíčová slova
• aging, immune system dysregulation, immunosenescence,
• MeSH
• adaptivní imunita MeSH
• imunitní systém MeSH
• imunosenescence * MeSH
• lidé MeSH
• senioři MeSH
• stárnutí MeSH
• vakcinace MeSH
• Check Tag
• lidé MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH

• Klíčová slova
• age, disease modifying therapies, immunosenescence, inflammaging, multiple sclerosis,
• Publikační typ
• úvodníky MeSH

The population of childhood cancer survivors (CCS) has grown rapidly in recent decades. Although cured of their original malignancy, these individuals are at increased risk of serious late effects, including age-associated complications. An impaired immune system has been linked to the emergence of these conditions in the elderly and CCS, likely due to senescent immune cell phenotypes accompanied by low-grade inflammation, which in the elderly is known as "inflammaging." Whether these observations in the elderly and CCS are underpinned by similar mechanisms is unclear. If so, existing knowledge on immunosenescent phenotypes and inflammaging might potentially serve to benefit CCS. We summarize recent findings on the immune changes in CCS and the elderly, and highlight the similarities and identify areas for future research. Improving our understanding of the underlying mechanisms and immunosenescent markers of accelerated immune aging might help us to identify individuals at increased risk of serious health complications.

• Klíčová slova
• accelerated aging, childhood cancer survivor, elderly, immunosenescence, late effects, low-grade inflammation, patient stratification,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Common variable immunodeficiency (CVID) is a heterogeneous group of diseases. Our aim was to define sub-groups of CVID patients with similar phenotypes and clinical characteristics. Using eight-color flow cytometry, we analyzed both B- and T-cell phenotypes in a cohort of 88 CVID patients and 48 healthy donors. A hierarchical clustering of probability binning "bins" yielded a separate cluster of 22 CVID patients with an abnormal phenotype. We showed coordinated proportional changes in naïve CD4+ T-cells (decreased), intermediate CD27- CD28+ CD4+ T-cells (increased) and CD21low B-cells (increased) that were stable for over three years. Moreover, the lymphocytes' immunophenotype in this patient cluster exhibited features of profound immunosenescence and chronic activation. Thrombocytopenia was only found in this cluster (36% of cases, manifested as Immune Thrombocytopenia (ITP) or Evans syndrome). Clinical complications more frequently found in these patients include lung fibrosis (in 59% of cases) and bronchiectasis (55%). The degree of severity of these symptoms corresponded to more deviation from normal levels with respect to CD21low B-cells, naïve CD4+ and CD27− CD28+ CD4+ T-cells. Next-generation sequencing did not reveal any common genetic background. We delineate a subgroup of CVID patients with activated and immunosenescent immunophenotype of lymphocytes and distinct set of clinical complications without common genetic background.

• MeSH
• aktivace lymfocytů MeSH
• B-lymfocyty imunologie   MeSH
• běžná variabilní imunodeficience imunologie   MeSH
• CD4-pozitivní T-lymfocyty imunologie   MeSH
• dospělí MeSH
• fenotyp MeSH
• fibróza MeSH
• idiopatická trombocytopenická purpura imunologie   MeSH
• imunosenescence MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• plíce patologie   MeSH
• průtoková cytometrie MeSH
• senioři MeSH
• separace buněk MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

RATIONALE: There is mounting evidence of a higher incidence of coronary heart disease in cytomegalovirus-seropositive individuals. OBJECTIVE: The aim of this study was to investigate whether acute myocardial infarction triggers an inflammatory T-cell response that might lead to accelerated immunosenescence in cytomegalovirus-seropositive patients. METHODS AND RESULTS: Thirty-four patients with acute myocardial infarction undergoing primary percutaneous coronary intervention were longitudinally studied within 3 months after reperfusion (Cohort A). In addition, 54 patients with acute myocardial infarction and chronic myocardial infarction were analyzed in a cross-sectional study (Cohort B). Cytomegalovirus-seropositive patients demonstrated a greater fall in the concentration of terminally differentiated CD8 effector memory T cells (TEMRA) in peripheral blood during the first 30 minutes of reperfusion compared with cytomegalovirus-seronegative patients (-192 versus -63 cells/μL; P=0.008), correlating with the expression of programmed cell death-1 before primary percutaneous coronary intervention (r=0.8; P=0.0002). A significant proportion of TEMRA cells remained depleted for ≥3 months in cytomegalovirus-seropositive patients. Using high-throughput 13-parameter flow cytometry and human leukocyte antigen class I cytomegalovirus-specific dextramers, we confirmed an acute and persistent depletion of terminally differentiated TEMRA and cytomegalovirus-specific CD8(+) cells in cytomegalovirus-seropositive patients. Long-term reconstitution of the TEMRA pool in chronic cytomegalovirus-seropositive postmyocardial infarction patients was associated with signs of terminal differentiation including an increase in killer cell lectin-like receptor subfamily G member 1 and shorter telomere length in CD8(+) T cells (2225 versus 3397 bp; P<0.001). CONCLUSIONS: Myocardial ischemia and reperfusion in cytomegalovirus-seropositive patients undergoing primary percutaneous coronary intervention leads to acute loss of antigen-specific, terminally differentiated CD8 T cells, possibly through programmed cell death-1-dependent programmed cell death. Our results suggest that acute myocardial infarction and reperfusion accelerate immunosenescence in cytomegalovirus-seropositive patients.

• Klíčová slova
• aging, cytotoxic T-lymphocytes, human cytomegalovirus, myocardial infarction, programmed cell death 1, reperfusion, telomere,
• MeSH
• antigeny CD8 krev   MeSH
• CD8-pozitivní T-lymfocyty imunologie   metabolismus   MeSH
• Cytomegalovirus imunologie   metabolismus   MeSH
• ischemická choroba srdeční krev   epidemiologie   virologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• longitudinální studie MeSH
• průřezové studie MeSH
• reperfuze myokardu metody   MeSH
• senioři MeSH
• stárnutí buněk fyziologie   MeSH
• syndromy imunologické nedostatečnosti krev   epidemiologie   virologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antigeny CD8 MeSH

The immune system develops from childhood until the late age. Each of these periods has its own specialities. Aging is typical for immunity, depending on the conversion of hematogenous bone marrow to adipose, involution of the thymus and persistent viral infections (e.g. CMV). In the elderly, whose numbers have been increasing in recent decades, there is a need to understand the changes in the immune system also called as immunosenescence. The substantial remodeling of the immune system during aging leads to a decline in its functional activity in both innate (complement, cytokines, granulocytes, NK cells, macrophages) and adaptive immunity (B lymphocytes and antibody production, T lymphocytes, cytokine production and cytotoxic response, NKT cells, regulatory T lymphocytes with suppressor activity) with advancing age, resulting in increased risk of chronic diseases, infections, autoimmunity and vaccination failure.

• Klíčová slova
• adaptive and innate immunity, immunosenescence, vaccination of the elderly,
• MeSH
• adaptivní imunita MeSH
• dítě MeSH
• imunosenescence * fyziologie   MeSH
• lidé MeSH
• senioři MeSH
• stárnutí fyziologie   MeSH
• T-lymfocyty MeSH
• vakcinace MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH

Almost all currently licensed disease-modifying therapies (DMTs) for MS treatment require prolonged if not lifelong administration. Yet, as people age, the immune system has increasingly reduced responsiveness, known as immunosenescence. Many MS DMTs reduce the responsiveness of the immune system, increasing the risks for infections and possibly cancers. As people with MS (pwMS) age, it is recognized that inflammatory MS activity declines. Several studies have addressed de-escalation of DMTs for relapsing MS under special circumstances. Here, we review evidence for de-escalating DMTs as a strategy that is particularly relevant to pwMS of older age. Treatment de-escalation can involve various strategies, such as extended or reduced dosing, switching from high-efficacy DMTs having higher risks to moderately effective DMTs with lesser risks, or treatment discontinuation. Studies have suggested that for natalizumab extended dosing maintained clinical efficacy while reducing the risk of PML. Extended interval dosing of ocrelizumab mitigated the decline of Ig levels. Retrospective and observational discontinuation studies demonstrate that age is an essential modifier of drug efficacy. Discontinuation of MS treatment in older patients has been associated with a stable disease course, while younger patients who discontinued treatment were more likely to experience new clinical activity. A recently completed 2-year randomized-controlled discontinuation study in 260 stable pwMS > 55 years found stable clinical multiple sclerosis with only a small increased risk of new MRI activity upon discontinuation. DMT de-escalation or discontinuation in MS patients older than 55 years may be non-inferior to continued treatment with immunosuppressive agents having higher health risks. However, despite several small studies, a definite conclusion about treatment de-escalation in older pwMS will require larger and longer studies. Ideally, comparison of de-escalation versus continuation versus discontinuation of DMTs should be done by prospective randomized-controlled trials enrolling sufficient numbers of subjects to allow comparisons for MS patients of both sexes within age groups, such as 55-59, 60-65, 66-69, etc. Optimally, such studies should be 3 years or longer and should incorporate testing for specific markers of immunosenescence (such as T-cell receptor excision circles) to account for differential aging of individuals.

• Klíčová slova
• De-escalation, Disease-modifying therapies, Immunosenescence, Multiple sclerosis,
• MeSH
• imunologické faktory aplikace a dávkování   MeSH
• lidé MeSH
• roztroušená skleróza * farmakoterapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• imunologické faktory MeSH