Impact of age-related immune dysfunction on risk of infections

Castle, Stephen

doi:10.1007/s003910070030

Cited by 57 publications

(32 citation statements)

References 47 publications

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“…These changes are often associated with important clinical manifestations such as increased susceptibility to infection and cancer incidence in the elderly population (Castle, 2000). However, the effect of aging on non-specific immunity and the production of pro-inflammatory cytokines is a more controversial subject.…”

Section: Discussionmentioning

confidence: 99%

Age‐dependent change in reactive oxygen species and nitric oxide generation by rat alveolar macrophages*

et al. 2003

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SummaryImmunosenescence is an age-associated dysregulation of the immune function, which contributes to increased susceptibility to disease in the elderly. Alveolar macrophages (AM) are known phagocytes that generate reactive oxygen species (ROS) and nitric oxide (NO), essential mediators for host defence. We studied phagocytosis, ROS and NO production in AM obtained from young, adult and senescent rats (1-2, 9-12 and 18-24 months old, respectively) after exposure to lipopolysaccharide (LPS, 0.1-10 µ µ µ µ g mL), 12-O-tetradecanoylphorbol 13-acetate (TPA, 0.1 µ µ µ µ g mL − − − − 1 ) or LPS + TPA in culture. Phagocytosis was significantly lower in control AM from adult rats than in AM from young animals. Nevertheless, AM from adult animals pretreated with LPS exhibited higher phagocytic capacity than AM from younger animals. ROS was identified by the NBT test at single cell level and quantified by automated image analysis. When TPA was added to all three populations, AM from adult and senescent animals responded more than AM from young animals. All LPS-stimulated AM produce more NO than controls. However, NO production increased three-, four-and two-fold in young, adult and senescent animals, respectively. Our results demonstrate that AM from young, adult and senescent animals display differential responsiveness to inflammatory mediators. Therefore, aging processes markedly affect AM metabolic functions and may further compromise the lung immune defence response, increasing adverse long-term health effects.

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Section: Discussionmentioning

confidence: 99%

Age‐dependent change in reactive oxygen species and nitric oxide generation by rat alveolar macrophages*

et al. 2003

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“…These include the accumulation of memory T cells, impaired functional responses in vitro, and a reduction in the response rate to vaccinations (5,8). These findings are associated with the phenomenon of immune senescence and are thought to underlie the increased rate of infectious disease that is seen in elderly individuals (7).…”

mentioning

confidence: 99%

The Cytomegalovirus-Specific CD4⁺T-Cell Response Expands with Age and Markedly Alters the CD4⁺T-Cell Repertoire

Pourgheysari

Khan

Best

et al. 2007

J Virol

187

141

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Immune function in the elderly is associated with a number of phenotypic and functional abnormalities, and this phenomenon of immune senescence is associated with increased susceptibility to infection. The immune response to pathogens frequently declines with age, but the CD8 ؉ T-cell response to cytomegalovirus (CMV) is unusual, as it demonstrates a significant expansion over time. Here we have documented the CD4 ؉ T-cell immune response to CMV in healthy donors of different ages. The magnitude of the CMV-specific CD4 ؉ T-cell immune response increases from a mean of 2.2% of the CD4 ؉ T-cell pool in donors below 50 years of age to 4.7% in donors aged over 65 years. In addition, CMV-specific CD4 ؉ T cells in elderly donors demonstrate decreased production of interleukin-2 and less dependence on costimulation. CMV seropositivity is associated with marked changes in the phenotype of the overall CD4؉ T-cell repertoire in healthy aged donors, including an increase in CD57؉ expression and a decrease in CD28 and CD27 expression, a phenotypic profile characteristic of immune senescence. This memory inflation of CMV-specific CD4 ؉ T cells contributes to evidence that CMV infection may be damaging to immune function in elderly individuals.Healthy aging is associated with the development of a number of phenotypic and functional abnormalities of the immune system. These include the accumulation of memory T cells, impaired functional responses in vitro, and a reduction in the response rate to vaccinations (5, 8). These findings are associated with the phenomenon of immune senescence and are thought to underlie the increased rate of infectious disease that is seen in elderly individuals (7).The magnitude of the cellular immune response to a number of pathogens has been studied in donors of different ages and has revealed that cellular immunity to viruses such as influenza virus and varicella-zoster virus decreases with advancing age (3). In marked contrast to these findings, the CD8 T-cell response to cytomegalovirus (CMV) increases markedly with age, such that it may represent over 40% of the CD8 ϩ T-cell pool (14,15). A similar observation has been seen with the CD8 T-cell immune response to murine cytomegalovirus (13). There has been speculation that this accumulation of memory CD8 T cells may itself contribute to features of immune senescence, and this idea has gained support from studies of elderly donors in whom CMV seropositivity is associated with the development of an immunological phenotype associated with impaired survival (16,29).CD4 T cells are important in the induction and regulation of the cellular immune response to pathogens, and an impaired CMV-specific CD4 T-cell immune response has been correlated with prolonged viral secretion following neonatal infection (10). Currently little is known with regard to how the magnitude or functional properties of the CD4 T-cell immune response to CMV are influenced by aging. Here we have studied the CMV-specific CD4 T-cell response to CMV viral lysate in a cohort of 30 ...

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“…Bei vielen chronischen Erkrankungen ist eine Funktionsbeeinträchtigung des Immunsystems zu finden [5,6]. Diese ist z. T. durch die Erkrankung bedingt, z. T. durch die notwendige Medikation.…”

Section: Besondere Immunologische Aspekte Bei Chronisch Krankenunclassified

“…Hier kann es zu einer erheblich reduzierten protektiven Effektivität kommen [5,6]. Zum Teil müssen hier Impfabstände verkürzt werden oder andere Applikati- Häufigkeit und Gefähr-dungspotential der Infektion [14] onswege gefunden werden.…”

Section: Besondere Immunologische Aspekte Bei Chronisch Krankenunclassified

Impfprävention bei chronischen Erkrankungen

Jelı́nek¹

2010

Praev Gesundheitsf

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Impfungen gehören zu den effektivsten prophylaktischen Maßnahmen in der Medizin. Die Erstimmunisierung bzw. Auffrischung von bereits im Kindesalter begonnenen Impfungen werden bei Erwachsenen häu-fig vernachlässigt. Die Immunisierungsraten in Deutschland zeigen mit steigendem Alter erhebliche Lücken, die nur durch intensive Aufklärung geschlossen werden können. Jeder Arztbesuch sollte stets auch zum Anlass genommen werden, den Impfstatus zu klären. Die Impfberatung sollte individuell auf den Patienten und seine Bedürfnisse abgestimmt sein und mögliche Complianceprobleme, auch finanzieller Natur, berücksichtigen. Eine beachtliche Zahl von Impfstoffen befindet sich derzeit in Entwicklung bzw. bereits in klinischer Prüfung, daher sind in den nächsten Jahren wesentliche Änderungen im Impfkalender zu erwarten. Andererseits hat gerade auch in Deutschland die Diskussion um die Sinnhaftigkeit von Impfungen erheblich zugenommen. Dies führt zu zusätzlicher Verunsicherung der Patienten. Der beratende Arzt tut gut daran, sich bezüglich neuer Impfstoffe auf dem Laufenden zu halten.

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Impact of age-related immune dysfunction on risk of infections

Cited by 57 publications

References 47 publications

Age‐dependent change in reactive oxygen species and nitric oxide generation by rat alveolar macrophages*

Age‐dependent change in reactive oxygen species and nitric oxide generation by rat alveolar macrophages*

The Cytomegalovirus-Specific CD4⁺T-Cell Response Expands with Age and Markedly Alters the CD4⁺T-Cell Repertoire

Impfprävention bei chronischen Erkrankungen

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Impact of age-related immune dysfunction on risk of infections

Cited by 57 publications

References 47 publications

Age‐dependent change in reactive oxygen species and nitric oxide generation by rat alveolar macrophages*

Age‐dependent change in reactive oxygen species and nitric oxide generation by rat alveolar macrophages*

The Cytomegalovirus-Specific CD4+T-Cell Response Expands with Age and Markedly Alters the CD4+T-Cell Repertoire

Impfprävention bei chronischen Erkrankungen

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The Cytomegalovirus-Specific CD4⁺T-Cell Response Expands with Age and Markedly Alters the CD4⁺T-Cell Repertoire