Role of Immunosenescence in Infections and Sepsis in the Elderly

  • Tamas Fulop
  • Steven Castle
  • Anis Larbi
  • Carl Fortin
  • Olivier Lesur
  • Graham Pawelec


It is well-known that infections and sepsis are increased in elderly subjects, and that the immune system changes with age. The question arises whether dysfunctionality of the immune system, or immunosenescence, contributes to this increased incidence of infections and if so, how. As the immune system evolved to protect against infection, the role of aging is likely to be important for the increased occurrence, progression and outcome of infections and sepsis in the elderly. However, the intricate multiple mechanisms that contribute to this increase are difficult to dissect with certitude and remain controversial. Immune alterations most likely to contribute to this overwhelming clinical burden of infections and sepsis will be reviewed in this chapter.


Elderly Subject Herpes Zoster Innate Immune System Adaptive Immune Response Influenza Vaccination 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Fulop T, Larbi A, Wikby A, Mocchegiani E, Hirokawa K, Pawelec G (2005) Dysregulation of T-cell function in the elderly : scientific basis and clinical implications. Drugs Aging 22;589–603PubMedCrossRefGoogle Scholar
  2. 2.
    Castle SC, Uyemura K, Fulop T, Makinodan T (2007) Host resistance and immune responses in advanced age. Clin Geriatr Med. 23;463–479PubMedCrossRefGoogle Scholar
  3. 3.
    Girard TD, Ely EW (2007) Bacteriemia and sepsis in older adult. Clin Geriatr Med. 23;633–647PubMedCrossRefGoogle Scholar
  4. 4.
    Castle SC, Uyemura K, Rafi A, Akande O, Makinodan T (2005) Comorbifity is a better predictor of impaired immunity than chronological age in older adults. J Am Geriatr Soc 53:1565–1568PubMedCrossRefGoogle Scholar
  5. 5.
    Castle SC (2000) Impact of age-related immune dysfunction on risk of infections. Z Gerontol Geriat 33:341–349CrossRefGoogle Scholar
  6. 6.
    Pawelec G (2006) Immunity and aging in man. Exp Ger 41:1239–1242CrossRefGoogle Scholar
  7. 7.
    Ahluhwalia N (2004) Aging, nutrition and immune function. J Nutr Health Aging 8:2–7Google Scholar
  8. 8.
    Castle SC (2000) Clinical relevance of age-related immune dysfunction. Clin Infect Dis 31:578–585PubMedCrossRefGoogle Scholar
  9. 9.
    Kovaiou RD, Herndler-Brandstetter D, Grubeck-Loebenstein B (2007) Age-related changes in immunity: implications for vaccination in the elderly. Expert Rev Mol Med 9:1–17PubMedCrossRefGoogle Scholar
  10. 10.
    Nichol KL, Nordin JD, Nelson DB, Mullooly JP, Hak E (2007) Effectiveness of influenza vaccine in the community-dwelling elderly. N Engl J Med. 1373–1381Google Scholar
  11. 11.
    Muszkat M, Friedman G, Dannenberg HD, Greenbaum E, Lipo M, Heymann Y, Zakay-Rones Z, Ben-Yehuda A (2003) Response to influenza vaccination in community and in nursing home residing elderly: relation to clinical factors. Exp Gerontol 38:1199–1203PubMedCrossRefGoogle Scholar
  12. 12.
    Vila Corcoles A (2007) Advances in pneumococcal vaccines: what are the advantages for the elderly? Drugs Aging 24;791–800PubMedGoogle Scholar
  13. 13.
    Oxman MN, Levin MJ (2008) Shingles Prevention Study Group. Vaccination against Herpes Zoster and Postherpetic Neuralgia. J Infect Dis 197 Suppl 2:S228–S236PubMedCrossRefGoogle Scholar
  14. 14.
    Rudman D, Hontanosas A, Cohen Z, Mattson DE (1988) Clinical correlates of bacteremia in a Veterans Administration extended care facility. J Am Geriatr Soc 36:726–732PubMedGoogle Scholar
  15. 15.
    Valenti WM, Trudell RG, Bentley DW (1978) Factors predisposing to oropharyngeal colonization with gram-negative bacilli in the aged. N Engl J Med 298;1108–1111PubMedGoogle Scholar
  16. 16.
    Dhainaut JF, Claessens YE, Janes J, Nelson DR Underlying disorders and their impact on the host response to infection.Clin Infect Dis 41 Suppl 7:S481–489Google Scholar
  17. 17.
    Marshall JC, Vincent JL, Fink MP, Cook DJ, Rubenfeld G, Foster D, Fisher CJ Jr, Faist E, Reinhart K (2003) Measures, markers, and mediators: toward a staging system for clinical sepsis. A report of the Fifth Toronto Sepsis Roundtable, Toronto, Ontario, Canada, (October 25-26, 2000). Crit Care Med 31:1560–1567PubMedCrossRefGoogle Scholar
  18. 18.
    Martin GS, Mannino DM, Moss M (2006) The effect of age on the development and outcome of adult sepsis. Crit Care Med 34:15–21PubMedCrossRefGoogle Scholar
  19. 19.
    Brun-Buisson C, Doyon F, Carlet J (1996) Bacteremia and severe sepsis in adults: a multicenter prospective survey in ICUs and wards of 24 hospitals. French Bacteremia-Sepsis Study Group. Am J Respir Crit Care Med 154(3 Pt 1):617–624PubMedGoogle Scholar
  20. 20.
    Baine WB, Yu W, Summe JP (2001) The epidemiology of hospitalization of elderly Americans for septicemia or bacteremia in 1991-1998. Application of Medicare claims data. Ann Epidemiol 11;118–126PubMedCrossRefGoogle Scholar
  21. 21.
    Diekema DJ, Pfaller MA, Jones RN (2002) SENTRY Participants Group. Age-related trends in pathogen frequency and antimicrobial susceptibility of bloodstream isolates in North America: SENTRY Antimicrobial Surveillance Program, (1997–2000). Int J Antimicrob Agents 20;412–418PubMedCrossRefGoogle Scholar
  22. 22.
    Lark RL, Saint S, Chenoweth C, Zemencuk JK, Lipsky BA, Plorde JJ (2001) Four-year prospective evaluation of community-acquired bacteremia: epidemiology, microbiology, and patient outcome. Diagn Microbiol Infect Dis 41:15–22PubMedCrossRefGoogle Scholar
  23. 23.
    Fulop T, Larbi A, Douziech N, Fortin C, Guérard KP, Lesur O, Khalil A, Dupuis G (2004) Signal transduction and functional changes in neutrophils with aging. Aging Cell. 3:217–226PubMedCrossRefGoogle Scholar
  24. 24.
    Guigoz Y, Doré J, Schiffrin EJ. (2008) The inflammatory status of old age can be nurtured from the intestinal environment. Curr Opin Clin Nutr Metab Care 11;13–20PubMedGoogle Scholar
  25. 25.
    Vasto S, Candore G, Balistreri CR, Caruso M, Colonna-Romano G, Grimaldi MP, Listi F, Nuzzo D, Lio D, Caruso C (2007) Inflammatory networks in ageing, age-related diseases and longevity. Mech Ageing Dev 128;83–91PubMedCrossRefGoogle Scholar
  26. 26.
    Dinarello CA (2007) A signal for the caspase-1 inflammasome free of TLR. Immunity 26;383–385PubMedCrossRefGoogle Scholar
  27. 27.
    P Drevot, C Langlet, XJ Guo, AM Bernard, O Colard, JP Chauvin, R Laserre, HT He (2002) TCR signal initiation machinery is pre-assembled and activated in a subset of membrane rafts. EMBO J 21:1899–1908PubMedCrossRefGoogle Scholar
  28. 28.
    Vasto S, Colonna-Romano G, Larbi A, Wikby A, Caruso C, Pawelec G (2007) Role of persistent CMV infection in configuring T cell immunity in the elderly. Immun Ageing 4:2PubMedCrossRefGoogle Scholar
  29. 29.
    Koch S, Larbi A, Ozcelik D, Solana R, Gouttefangeas C, Attig S, Wikby A, Strindhall J, Franceschi C, Pawelec G (2007) Cytomegalovirus infection: a driving force in human T cell immunosenescence. Ann N Y Acad Sci 1114;23–35PubMedCrossRefGoogle Scholar
  30. 30.
    Vescovini R, Biasini C, Fagnoni FF, Telera AR, Zanlari L, Pedrazzoni M, Bucci L, Monti D, Medici MC, Chezzi C, Franceschi C, Sansoni P (2007) Massive load of functional effector CD4+ and CD8+ T cells against cytomegalovirus in very old subjects. J Immunol 179;4283–4291PubMedGoogle Scholar
  31. 31.
    Effros RB (2004) Replicative senescence of CD8 T cells: effect of human aging. Exp Gerontol 39:517–524PubMedCrossRefGoogle Scholar
  32. 32.
    Sansoni P, Vescovini R, Fagnoni F, Biasini C, Zanni F, Zanlari L, Telera A, Lucchini G, Passeri G, Monti D, Franceschi C, Passeri M (2008) The immune system in extreme longevity. Exp Gerontol 43:61–65PubMedCrossRefGoogle Scholar
  33. 33.
    Ely KH, Roberts AD, Kohlmeier JE, Blackman MA, Woodland DL (2007) Aging and CD8+ T cell immunity to respiratory virus infections. Exp Gerontol 42:427–431PubMedCrossRefGoogle Scholar
  34. 34.
    Gruver AL, Hudson LL, Sempowski GD (2007) Immunosenescence of ageing. J Pathol 21:144–156CrossRefGoogle Scholar
  35. 35.
    Pawelec G, Hirokawa K, Fulop T (2001) T cell signalling with aging. Mech Ageing Dev 122:1613–1637PubMedCrossRefGoogle Scholar
  36. 36.
    Larbi A, Dupuis G, Khalil A, Douziech N, Fortin C, Fülöp T Jr (2006) Differential role of lipid rafts in the functions of CD4+ and CD8+ human T lymphocytes with aging. Cell Signal 18:1017–1030PubMedCrossRefGoogle Scholar
  37. 37.
    Franceschi C, Bonafe M, Valensin A, Olivieri F, De Luca M, Ottaviani E, De Benedictis G (2000) Inflamm-Aging. An evolutionary perspective on immunosenescence. Ann N Y Acad Sci 908:244–254PubMedCrossRefGoogle Scholar
  38. 38.
    Wikby A, Månsson IA, Johansson B, Strindhall J, Nilsson SE (2008) The immune risk profile is associated with age and gender: findings from three Swedish population studies of individuals 20-100 years of age. BiogerontologyGoogle Scholar
  39. 39.
    Martin GS, Mannino DM, Eaton S, Moss M (2003) The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med 348:1546–1554PubMedCrossRefGoogle Scholar
  40. 40.
    Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR (2001) Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med 29;1303–1310PubMedCrossRefGoogle Scholar
  41. 41.
    Zarbock A, Ley K (2008) Mechanisms and consequences of neutrophil interaction with the endothelium. Am J Pathol 172:1–7PubMedCrossRefGoogle Scholar
  42. 42.
    Fülöp T Jr, Fóris G, Wórum I, Paragh G, Leövey A (1985) Age related variations of some polymorphonuclear leukocyte functions. Mech Ageing Dev 29(1):1–8PubMedCrossRefGoogle Scholar
  43. 43.
    Tortorella C, Simone O, Piazzolla G, Stella I, Antonaci S (2007) Age-related impairment of GM-CSF-induced signalling in neutrophils: role of SHP-1 and SOCS proteins. Ageing Res Rev 6:81–93PubMedCrossRefGoogle Scholar
  44. 44.
    Ferrucci L, Harris TB, Guralnik JM, Tracy RP, Corti MC, Cohen HJ, Penninx B, Pahor M, Wallace R, Havlik RJ (1999) Serum IL-6 level and the development of disability in older persons. J Am Geriatr Soc 47(6):639–646PubMedGoogle Scholar
  45. 45.
    Maggio M, Guralnik JM, Longo DL, Ferrucci L (2006) Interleukin-6 in aging and chronic disease: a magnificent pathway. J Gerontol A Biol Sci Med Sci 61(6):575–584PubMedGoogle Scholar
  46. 46.
    Cohen HJ, Harris T, Pieper CF (2003) Coagulation and activation of inflammatory pathways in the development of functional decline and mortality in the elderly. Am J Med 114:180–187PubMedCrossRefGoogle Scholar
  47. 47.
    Ono S, Aosasa S, Tsujimoto H, Ueno C, Mochizuki H (2000) Increased monocyte activation in elderly patients after surgical stress. Eur Surg Res. 33:33–38CrossRefGoogle Scholar
  48. 48.
    Krabbe KS, Bruunsgaard H, Hansen CM, Møller K, Fonsmark L, Qvist J, Madsen PL, Kronborg G, Andersen HO, Skinhøj P, Pedersen BK (2001) Ageing is associated with a prolonged fever response in human endotoxemia. Clin Diagn Lab Immunol 8:333–338PubMedCrossRefGoogle Scholar
  49. 49.
    Bruunsgaard H, Skinhøj P, Qvist J, Pedersen BK (1999) Elderly humans show prolonged in vivo inflammatory activity during pneumococcal infections. J Infect Dis 180:551–554PubMedCrossRefGoogle Scholar
  50. 50.
    Marik PE, Zaloga GP (2001) NORASEPT II Study Investigators. North American Sepsis Trial II. The effect of aging on circulating levels of proinflammatory cytokines during septic shock. Norasept II Study Investigators. J Am Geriatr Soc 49:5–9PubMedCrossRefGoogle Scholar
  51. 51.
    Wheeler AP, Bernard GR (1999) Treating patients with severe sepsis. N Engl J Med 340:207–214PubMedCrossRefGoogle Scholar
  52. 52.
    Woodland DL, Hogan RJ, Zhong W (2001) Cellular immunity and memory to respiratory virus infections. Immunol Res 24:53–67PubMedCrossRefGoogle Scholar
  53. 53.
    Linton PJ, Haynes L, Tsui L, Zhang X, Swain S (1997) From naive to effector-alterations with aging. Immunol Rev 160:9–18PubMedCrossRefGoogle Scholar
  54. 54.
    Burns EA, Goodwin JS (1997) Immunodeficiency of aging. Drugs Aging 11:374–397PubMedCrossRefGoogle Scholar
  55. 55.
    Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, Seeman T, Tracy R, Kop WJ, Burke G, McBurnie MA (2001) Cardiovascular Health Study Collaborative Research Group. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci 56: M146–M156PubMedGoogle Scholar
  56. 56.
    Herndler-Brandstetter D, Cioca DP, Grubeck-Loebenstein B (2006) Immunizations in the elderly: do they live up to their promise? Wien Med Wochenschr 156:130–141PubMedCrossRefGoogle Scholar
  57. 57.
    Sato M, Saito R, Tanabe N, Nishikawa M, Sasaki A, Gejyo F, Suzuki H (2005) Antibody response to influenza vaccination in nursing home residents and healthcare workers during four successive seasons in Niigata, Japan. Infect Control Hosp Epidemiol 26;859–866PubMedCrossRefGoogle Scholar
  58. 58.
    Muszkat M, Greenbaum E, Ben-Yehuda A, Oster M, Yeu’l E, Heimann S, Levy R, Friedman G, Zakay-Rones Z (2003) Local and systemic immune response in nursing-home elderly following intranasal or intramuscular immunization with inactivated influenza vaccine. Vaccine 7;21(11-12):1180–1186CrossRefGoogle Scholar
  59. 59.
    McElhany JE (2005) The unmet need in the elderly: designing new influenza vaccines for older adults.Vaccine 23 Suppl 1:S10–25CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2009

Authors and Affiliations

  • Tamas Fulop
    • 1
  • Steven Castle
    • 2
  • Anis Larbi
    • 3
  • Carl Fortin
    • 4
  • Olivier Lesur
    • 4
  • Graham Pawelec
    • 3
  1. 1.Research Center on Aging, Immunology Program Geriatric Division, Faculty of MedicineUniversity of SherbrookeSherbrookeCanada
  2. 2.Geriatric Research Education and Clinical Center (GRECC), VA Greater Los Angeles Healthcare systemUCLA School of MedicineLos AngelesUSA
  3. 3.Ageing and Tumour Immunology Group, Center for Medical ResearchUniversity of Tübingen Medical SchoolTübingenGermany
  4. 4.Graduate Immunology Program Division of Pulmonology Department of Medicine Faculty of MedicineUniversity of SherbrookeSherbrooke

Personalised recommendations