Skip to main content

Immunological changes in the elderly

Abstract

Immunosenescence is a complex remodelling of the immune system which may contribute significantly to morbidity and mortality in the elderly. Much evidence suggests an association between immune function and longevity. It was advanced that individuals who have survived in good health to the maximum life span are equipped with optimal cell defense mechanisms. Despite the great number of studies on the immune system in the elderly, little is known of the biological basis of immunosenescence in humans. This is partly due to the contrasting results often obtained by the various investigators. One source of discrepancy is that diseases are frequent in aging, and the alterations observed in the immune parameters of the elderly could be a cause or alternatively a consequence of the underlying pathological processes. Undoubtedly some diseases to which aged people are particularly susceptible, such as infectious, autoimmune and neoplastic pathologies, include dysregulation of several immune functions in their pathogenesis. On the other hand, recent studies in healthy centenarians suggest that the immunological changes observed during aging are consistent with a reshaping, rather than a generalized deterioration, of the main immune functions. Considering that the number of old people is dramatically increasing, and that geriatric pathology is becoming an important aspect of clinical practice, it seems particularly interesting to review the peculiar findings in the immune system of the elderly so as to better understand their susceptibility to certain diseases, and the links between health and longevity.

This is a preview of subscription content, access via your institution.

References

  1. Pawelec G., Rehbein A., Haehnel K., Merl A., Adibzadeh M.: Human T-cell clones in long-term culture as a model of immunosenescence. Immunol. Rev. 160: 31–42, 1997.

    CAS  PubMed  Article  Google Scholar 

  2. Cossarizza A., Ortolani C., Monti D., Franceschi C.: Cytometric analysis of immunosenescence. Cytometry 27: 297–313, 1997.

    CAS  PubMed  Article  Google Scholar 

  3. Hirokawa K.: Understanding the mechanism of age-related decline in immune function. Nutr. Rev. 50: 361–366, 1992.

    CAS  PubMed  Article  Google Scholar 

  4. Pawelec G., Solana R.: Immunosenescence. Immunol. Today 18: 514–516, 1997.

    CAS  PubMed  Article  Google Scholar 

  5. Franceschi C., Monti D., Sansoni P., Cossarizza A.: The immunology of exceptional individuals: the lesson of centenarians. Immunol. Today 16: 12–16, 1995.

    CAS  PubMed  Article  Google Scholar 

  6. Ligthart G.J., Corberand J.X., Fournier C., Garanaud P., Hijmans W., Kennes B., Muller-Hermelink H.K., Steinmann G.G.: Admission criteria for immunogerontological studies in man: the SENIEUR protocol. Mech. Ageing Dev. 28: 47–55, 1984.

    CAS  PubMed  Article  Google Scholar 

  7. Ligthart G.J., Corberand J.X., Geertzen H.G.M., Meinders A.E., Knook D.L., Hijmans W.: Necessity of the assessment of health status in human immunogerontological studies: evaluation of the SENIEUR protocol. Mech. Ageing Dev. 55: 89–105, 1990.

    CAS  PubMed  Article  Google Scholar 

  8. Pawelec G., Adibzadeh M., Pohla H., Schaudt K.: Immunosenescence: ageing of the immune system. Immunol. Today 16: 420–422, 1995.

    CAS  PubMed  Article  Google Scholar 

  9. Louria D.B., Sen P., Sherer C.B., Farrer W.E.: Infections in older patients: a systematic clinical approach. Geriatrics 48: 28–34, 1993.

    CAS  PubMed  Google Scholar 

  10. Monti D., Grassilli E., Troiano L., Cossarizza A., Salvioli S., Barbieri D., Agnesini C., Bettuzzi S., Ingletti M.C., Corti A., Franceschi C.: Senescence, immortalization and apoptosis: an intriguing relationship. Ann. N.Y. Acad. Sci. 673: 70–82, 1992.

    CAS  PubMed  Article  Google Scholar 

  11. Mountz J.D., Wu J., Zhou T., Hsu H.C.: Cell death and longevity: implications of Fas-mediated apoptosis in T-cell senescence. Immunol. Rev. 160: 19–30, 1997.

    CAS  PubMed  Article  Google Scholar 

  12. Wayne S.J., Rhyne R.L., Garry P.J., Goodwin J.S.: Cellmediated immunity as a predictor of morbidity and mortality in subjects over 60. J. Gerontol. 45: 45–48, 1990.

    Article  Google Scholar 

  13. Ferguson F.G., Wikby A., Maxson P., Olsson J., Johansson B.: Immune parameters in a longitudinal study of a very old population of Swedish people: a comparison between survivors and nonsurvivors. J. Gerontol. 50: B378–B382, 1995.

    CAS  Article  Google Scholar 

  14. Powers D.C., Belshe R.B.: Effect of age on cytotoxic T lymphocyte memory as well as serum and local antibody responses elicited by inactivated influenza virus vaccine. J. Infect. Dis. 167: 584–592, 1993.

    CAS  PubMed  Article  Google Scholar 

  15. Hirokawa K., Utsuyama M., Kasai M., Jurachima C., Ishijima S., Zeng Y.X.: Understanding the mechanism of the age-related change of thymic function to promote T cell differentiation. Immunol. Lett. 40: 269–277, 1994.

    CAS  PubMed  Article  Google Scholar 

  16. Thoman M.L.: Early steps in T cell development are affected by aging. Cell. Immunol. 178: 117–123, 1997.

    CAS  PubMed  Article  Google Scholar 

  17. Mackall C.L., Gress R.E.: Thymic aging and T cell regeneration. Immunol. Rev. 160: 91–102, 1997.

    CAS  PubMed  Article  Google Scholar 

  18. Engwerda C.R., Handwerger B.S., Fox B.S.: Aged T cells are hyporesponsive to co-stimulation mediated by CD28. J. Immunol. 152: 3740–3747, 1994.

    CAS  PubMed  Google Scholar 

  19. Brosche T., Platt D.: Nutritional factors and age-associated changes in cellular immunity and phagocytosis: a mini-review. Aging Immunol. Infect. Dis. 6: 31–42, 1995.

    Google Scholar 

  20. Quaglino D., Ginaldi L., Furia N., De Martinis M.: The effect of age on hemopoiesis. Aging Clin. Exp. Res. 8: 1–12, 1996.

    CAS  Google Scholar 

  21. Sansoni P., Cossarizza A., Brianti V., Fagnoni F., Snelli G., Monti D., Marcato A., Passeri G., Ortolani C., Forti E., Fagiolo U., Passeri M., Franceschi C.: Lymphocyte subsets and natural killer cell activity in healthy old people and centenarians. Blood 80: 2767–2773, 1993.

    Google Scholar 

  22. Cossarizza A., Ortolani C., Paganelli R., Barbieri D., Monti D., Sansoni P., Fagiolo U., Castellani G., Bersani F., Londei M., Franceschi C.: CD45 isoforms expression on CD4+ and CD8+ T cells throughout life, from newborns to centenarians: implications for T cell memory. Mech. Ageing Dev. 86: 173–195, 1996.

    CAS  PubMed  Article  Google Scholar 

  23. Swain S.L., Bradley L.M., Croft M., Dubey C., Haynes L., Rogers P., Zhang X., Bradley L.M.: From naive to memory T cells. Immunol. Rev. 150: 143–167, 1996.

    CAS  PubMed  Article  Google Scholar 

  24. Linton P.J., Haynes L., Tsui L., Zhang X., Swain S.: From naive to effector — alterations with aging. Immunol. Rev. 160: 9–18, 1997.

    CAS  PubMed  Article  Google Scholar 

  25. Thoman M.L.: Effects of the aged microenvironment on CD4+ T cell maturation. Mech. Ageing Dev. 96: 75–88, 1997.

    CAS  PubMed  Article  Google Scholar 

  26. Flurkey K., Stadecker M., Miller R.A.: Memory T lymphocyte hyporesponsiveness to non-cognate stimuli: a key factor in age-related immunodeficiency. Eur. J. Immunol. 22: 931–935, 1992.

    CAS  PubMed  Article  Google Scholar 

  27. Miyaji C., Watanabe H., Minagawa M., Toma H., Kawamura T., Noiiara Y., Nozaki H., Sato Y., Abo T.: Numerical and functional characteristics of lymphocyte subsets in centenarians. J. Clin. Immunol. 17: 420–429, 1997.

    CAS  PubMed  Article  Google Scholar 

  28. Liu J., Wang S., Liu H., Yang L., Nan G.: The monitoring biomarker for immune function of lymphocytes in the elderly. Mech. Ageing Dev. 94: 177–182, 1997.

    CAS  PubMed  Article  Google Scholar 

  29. Jackola D.R., Ruger J.K., Miller R.A.: Age-associated changes in human T cell phenotype and function. Aging Clin. Exp. Res. 6: 25–34, 1994.

    CAS  Article  Google Scholar 

  30. Miller R.A., Garcia G., Kirk C.J., Witkowski J.M.: Early activation defects in T lymphocytes from aged mice. Immunol. Rev. 160: 79–90, 1997.

    CAS  PubMed  Article  Google Scholar 

  31. Okumura M., Fujii Y., Inada K., Nakahara K., Matsuda H.: Both CD45RA+ CD45RA- subpopulations of CD8+ T cells contain cells with high levels of lymphocyte function associated antigen-1 expression, a phenotype of primed T cells. J. Immunol. 150: 429–437, 1993.

    CAS  PubMed  Google Scholar 

  32. Pahlavani M.A., Richardson A.: The effect of age on the expression of interleukin-2. Mech. Ageing Dev. 89: 125–154, 1996.

    CAS  PubMed  Article  Google Scholar 

  33. Frasca D., Pucci S., Goso C., Barattini P., Barile S., Pioli C., Doria G.: Regulation of cytokine production in aging: use of recombinant cytokines to upregulate mitogen-stimulated spleen cells. Mech. Ageing Dev. 93: 157–169, 1997.

    CAS  PubMed  Article  Google Scholar 

  34. Shearer G.M.: Th1/Th2 changes in aging. Mech. Ageing Dev. 94: 1–5, 1997.

    CAS  PubMed  Article  Google Scholar 

  35. Morellini M., Trabace S., Lulli P., Cappellacci S., Brioli G., Orrù D., Pennesi G., Monti D., Cossarizza A., Lambert Gardini S., Sansoni P., Franceschi C.: HLA antigens and aging. Ann. N.Y. Acad. Sci. 663: 499–500, 1992.

    CAS  PubMed  Article  Google Scholar 

  36. Krishnaraj R.: Senescence and cytokines modulate the NK cell expression. Mech. Ageing Dev. 96: 89–101, 1997.

    CAS  PubMed  Article  Google Scholar 

  37. Powers D.C., Manning M.C., Morley J.E., Flood J.F.: Age-related changes in lymphoproliferation, cytotoxic T lymphocyte responses, and natural killer activity of senescence accelerated mouse (SAM)-P/8 and SAM-R/1 substrains. Aging Immunol. Infect. Dis. 6: 43–52, 1995.

    Google Scholar 

  38. Ligthart G.J., Schuit H.R.E., Hijmans W.: Natural killer function is not diminished in the healthy aged and is proportional to the number of NK cells in the perypheral blood. Immunology 68: 396–402, 1989.

    CAS  PubMed  Google Scholar 

  39. Franceschi C., Monti D., Cossarizza A., Fagnono F., Passeri G., Sansoni P.: Aging, longevity and cancer. Studies in Down’s syndrome and in centenarians. Ann. N.Y. Acad. Sci. 621: 428–440, 1991.

    CAS  PubMed  Article  Google Scholar 

  40. Levy S.M., Herberman R.B., Lee J., Whiteside T., Beadle M., Heiden L., Simons A.: Persistently low natural killer cell activity, age, and environmental stress as predictors of infectious morbidity. Natl. Immunol. Cell Growth Regul. 10: 289–307, 1991.

    CAS  Google Scholar 

  41. Rabatic S., Sabioncello A., Dekaris D., Kardum I.: Age-related changes in functions of peripheral blood phagocytes. Mech. Ageing Dev. 45: 223–229, 1988.

    CAS  PubMed  Article  Google Scholar 

  42. Esparza B., Sanchez H., Ruiz M., Barranquero M., Sabino E., Merino F.: Neutrophil function in elderly persons assessed by flow cytometry. Immunol. Invest. 25: 185–190, 1996.

    CAS  PubMed  Article  Google Scholar 

  43. Paganelli R., Scala E., Quinti I., Ansotegui I.J.: Humoral immunity in aging. Aging Clin. Exp. Res. 6: 143–150, 1994.

    CAS  Article  Google Scholar 

  44. Klinman N.R., Kline G.H.: The B-cell biology of aging. Immunol. Rev. 160: 103–114, 1997.

    CAS  PubMed  Article  Google Scholar 

  45. Ligthart G.J., Radl J., Corberand J.X., Van Nieuwkoop J.E., Van Staalduinen G.J., Van Helmond D.J.W., Hijmans W.: Monoclonal gammopathies in human aging: increased occurrence with age and correlation with healthy status. Mech. Ageing Dev. 52: 235–243, 1990.

    CAS  PubMed  Article  Google Scholar 

  46. Louria D.B., Sen P., Sherer C.B., Farrer W.E.: Infections in older patients: a systematic clinical approach. Geriatrics 48: 28–34, 1993.

    CAS  PubMed  Google Scholar 

  47. Arreaza E.E., Gibbons J.J., Siskind G.W., Weksler M.E.: Lower antibody response to tetanus toxoid associated with higher auto-anti-idiotypic antibody in old compared with young humans. Clin. Exp. Immunol. 92: 169–173, 1993.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  48. Paganelli R., Quinti I., Fagiolo U., Cossarizza A., Ortolani C., Guerra E., Sansoni P., Pucillo L.P., Cozzi E., Bertollo L., Monti D., Franceschi C.: Changes in circulating B cells and immunoglobulin classes and subclasses in a healthy aged population. Clin. Exp. Immunol. 90: 351–354, 1992.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  49. Chen X., Kearney J.F.: Generation and function of natural self-reactive B cells. Semin. Immunol. 8: 19–27, 1996.

    CAS  PubMed  Article  Google Scholar 

  50. Mariotti S., Sansoni P., Barbesino G., Caturegli P., Monti D., Cossarizza A., Giacomelli T., Passeri G., Fagiolo U., Pinchera A., Franceschi C.: Thyroid and other organ-specific autoantibodies in healthy centenarians. Lancet 339: 1506–1508, 1992.

    CAS  PubMed  Article  Google Scholar 

  51. Song H., Price P.W., Cerny J.: Age-related changes in antibody repertoire: contribution from T-cells. Immunol. Rev. 160: 55–62, 1997.

    CAS  PubMed  Article  Google Scholar 

  52. Yang X., Sterda J., Cerny J.: Relative contribution of T and B cells to hypermutation and selection of antibody in germinal centers of aged mice. J. Exp. Med. 183: 959–970, 1996.

    CAS  PubMed  Article  Google Scholar 

  53. Zheng B., Han S., Takahashi Y., Kelsoe G.: Immunosenescence and germinal center reaction. Immunol. Rev. 160: 63–77, 1997.

    CAS  PubMed  Article  Google Scholar 

  54. Doria G., Frasca D.: Genes, immunity, and senescence: looking for a link. Immunol. Rev. 160: 159–170, 1997.

    CAS  PubMed  Article  Google Scholar 

  55. Barinaga M.: How long is the human life-span? Science 254: 936–938, 1991.

    CAS  PubMed  Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to L. Ginaldi M.D..

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Ginaldi, L., De Martinis, M., D’Ostilio, A. et al. Immunological changes in the elderly. Aging Clin Exp Res 11, 281–286 (1999). https://doi.org/10.1007/BF03339801

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03339801

Key words

  • Aging
  • immune system