Immunosenescence

From Wikipedia, the free encyclopedia
Jump to: navigation, search

Immunosenescence refers to the gradual deterioration of the immune system brought on by natural age advancement. It involves both the host’s capacity to respond to infections and the development of long-term immune memory, especially by vaccination.[1] This age-associated immune deficiency is ubiquitous and found in both long- and short-living species as a function of their age relative to life expectancy rather than chronological time.[2] It is considered a major contributory factor to the increased frequency of morbidity and mortality among the elderly.

Immunosenescence is not a random deteriorative phenomenon, rather it appears to inversely repeat an evolutionary pattern and most of the parameters affected by immunosenescence appear to be under genetic control.[3] Immunosenescence can also be sometimes envisaged as the result of the continuous challenge of the unavoidable exposure to a variety of antigens such as viruses and bacteria.[4]

Overview of the age-associated decline in immune function[edit]

Immunosenescence is a multifactorial condition leading to many pathologically significant health problems in the aged population. Some of the age-dependent biological changes that contribute to the onset of immunosenescence are listed below:

As age advances, there is decline in both the production of new naive lymphocytes and the functional competence of memory cell populations. This has been implicated in the increasing frequency and severity of diseases such as cancer, chronic inflammatory disorders and autoimmunity.[12] A problem of infections in the elderly is that they frequently present with non-specific signs and symptoms, and clues of focal infection are often absent or obscured by underlying chronic conditions.[2] Ultimately, this provides problems in diagnosis and subsequently, treatment.

In addition to changes in immune responses, the beneficial effects of inflammation devoted to the neutralisation of dangerous and harmful agents early in life and in adulthood become detrimental late in life in a period largely not foreseen by evolution, according to the antagonistic pleiotropy theory of aging.[13] It should be further noted that changes in the lymphoid compartment is not solely responsible for the malfunctioning of the immune system in the elderly. Although myeloid cell production does not seem to decline with age, macrophages become dysregulated as a consequence of environmental changes.[14]

T-cell functional dysregulation as a biomarker for immunosenescence[edit]

The functional capacity of T-cells is most influenced by the effects of aging. In fact, age-related alterations are evident in all stages of T-cell development, making them a significant factor in the development of immunosenescence.[15] After birth, the decline of T-cell function begins with the progressive involution of the thymus, which is the organ essential for T-cell maturation following the migration of precursor cells from the bone marrow. This age-associated decrease of thymic epithelial volume results in a reduction/exhaustion on the number of thymocytes (i.e. pre-mature T-cells), thus reducing output of peripheral naïve T-cells.[16][17] Once matured and circulating throughout the peripheral system, T-cells still undergo deleterious age-dependent changes. Together with the age-related thymic involution, and the consequent age-related decrease of thymic output of new T cells, this situation leaves the body practically devoid of virgin T cells, which makes the body more prone to a variety of infectious and non-infectious diseases.[4] T-cell components associated with immunosenescence include:

References[edit]

  1. ^ Muszkat, M; E. Greenbaum; A. Ben-Yehuda; M. Oster; E. Yeu'l; S. Heimann; R. Levy; G. Friedman; Z. Zakay-Rones (2003). "Local and systemic immune response in nursing-home elderly following intranasal or intramuscular immunization with inactivated influenza vaccine". Vaccine 21 (11–12): 1180–1186. doi:10.1016/S0264-410X(02)00481-4. PMID 12559796. 
  2. ^ a b Ginaldi, L.; M.F. Loreto, M.P. Corsi, M. Modesti, and M. de Martinis (2001). "Immunosenescence and infectious diseases". Microbes and Infection 3 (10): 851–857. doi:10.1016/S1286-4579(01)01443-5. PMID 11580980. 
  3. ^ a b Franceschi, C.; S. Valensin, F. Fagnoni, C. Barbi and M. Bonafe (1999). "Biomarkers of immunosenescence within an evolutionary perspective: the challenge of heterogeneity and the role of antigenic load". Experimental Gerontology 34 (8): 911–921. doi:10.1016/S0531-5565(99)00068-6. 
  4. ^ a b Franceschi, C.; M. Bonafè and S. Valensin (2000). "Human immunosenescence: the prevailing of innate immunity, the failing of clonotypic immunity, and the filling of immunological space". Vaccine 18 (16): 1717–1720. doi:10.1016/S0264-410X(99)00513-7. PMID 10689155. 
  5. ^ Ito, K; A. Hirao, F. Arai, S. Matsuoka, K. Takubo, I. Hamaguchi, K. Nomiyama, K. Hosokawa, K. Sakurada, N. Nakagata, Y. Ikeda, T. W. Mak, and T. Suda. (2004). "Regulation of oxidative stress by ATM is required for self-renewal of haematopoietic stem cells". Nature 431 (7011): 997–1002. doi:10.1038/nature02989. PMID 15496926. 
  6. ^ Lord, J.M.; S. Butcher; V. Killampali; D. Lascelles; M. Salmon (2001). "Neutrophil ageing and immunesenescence". Mech Ageing Dev 122 (14): 1521–1535. doi:10.1016/S0047-6374(01)00285-8. PMID 11511394. 
  7. ^ Strout, R.D.; J. Suttles. (2005). "Immunosenescence and macrophage functional plasticity: dysregulation of macrophage function by age-associated microenvironmental changes". Immunol Rev 205: 60–71. doi:10.1111/j.0105-2896.2005.00260.x. PMC 1201508. PMID 15882345. 
  8. ^ Bruunsgaard, H.; A. N. Pedersen, M. Schroll, P. Skinhoj, and B. K. Pedersen. (2001). "Decreased natural killer cell activity is associated with atherosclerosis in elderly humans". Exp Gerontol 37 (1): 127–136. doi:10.1016/S0531-5565(01)00162-0. PMID 11738153. 
  9. ^ a b Mocchegiani, E; M. Malavolta (2004). "NK and NKT cell functions in immunosenescence". Aging Cell 3 (4): 177–184. doi:10.1111/j.1474-9728.2004.00107.x. PMID 15268751. 
  10. ^ Uyemura, K.; S. C. Castle; T. Makinodan (2002). "The frail elderly: role of dendritic cells in the susceptibility of infection". Mech Ageing Dev 123 (8): 955–962. doi:10.1016/S0047-6374(02)00033-7. PMID 12044944. 
  11. ^ Han, S.; K. Yang; Z. Ozen; W. Peng; E. Marinova; G. Kelsoe; B. Zheng (2003). "Enhanced differentiation of splenic plasma cells but diminished long-lived high-affinity bone marrow plasma cells in aged mice". J Immunol 170 (3): 1267–1273. doi:10.4049/jimmunol.170.3.1267. PMID 12538685. 
  12. ^ Hakim, F.T.; R.E. Gress (2007). "Immunosenescence: deficits in adaptive immunity in elderly". Tissue antigens 70 (3): 179–189. doi:10.1111/j.1399-0039.2007.00891.x. PMID 17661905. 
  13. ^ Franceschi, C.; M. Bonafe, S. Valensin, F. Olivieri, M. de Luca, E. Ottaviani and G. de Benedictis (2000). "Inflamm-aging: An Evolutionary Perspective on Immunosenescence". Annals of the New York Academy of Sciences 908: 244–254. doi:10.1111/j.1749-6632.2000.tb06651.x. PMID 10911963. 
  14. ^ Cambier, J. (2005). "Immunosenescence: a problem of lymphopoiesis, homeostasis, microenvironment, and signaling". Immunological reviews 205: 5–6. doi:10.1111/j.0105-2896.2005.00276.x. PMID 15882340. 
  15. ^ Linton, P.-J; J. Lustgarten; M. Thoman (2006). "T cell function in the aged: Lessons learned from animal models". Clinical and Applied Immunology Reviews 6 (2): 73–97. doi:10.1016/j.cair.2006.06.001. 
  16. ^ Aspinall, R.; D. Andrew (2000). "Thymic involution in aging". J Clin Immunol 20 (4): 250–256. doi:10.1023/A:1006611518223. PMID 10939712. 
  17. ^ Min, H.; E. Montecino-Rodriguez; K. Dorshkind (2004). "Reduction in the developmental potential of intrathymic T cell progenitors with age". J Immunol 173 (1): 245–250. doi:10.4049/jimmunol.173.1.245. PMID 15210781. 
  18. ^ Lefebvre JS, Maue AC, Eaton SM, Lanthier PA, Tighe M, Haynes L. (2012). "The aged microenvironment contributes to the age-related functional defects of CD4 T cells in mice". Aging Cell 11 (5): 732–40. doi:10.1111/j.1474-9726.2012.00836.x. PMID 22607653. 
  19. ^ Fulop, T., Jr.; D. Gagne; A. C. Goulet; S. Desgeorges; G. Lacombe; M. Arcand; G. Dupuis (1999). "Age-related impairment of p56lck and ZAP-70 activities in human T lymphocytes activated through the TcR/CD3 complex". Exp Gerontol 34 (2): 197–216. doi:10.1016/S0531-5565(98)00061-8. PMID 10363787. 
  20. ^ a b Murciano, C.; E. Villamon; A. Yanez; J. E. O'Connor; D. Gozalbo; M. L. Gil (2006). "Impaired immune response to Candida albicans in aged mice". J Med Microbiol 55 (Pt 12): 1649–1656. doi:10.1099/jmm.0.46740-0. PMID 17108267. 
  21. ^ a b c Voehringer, D.; M. Koschella; H. Pircher (2002). "Lack of proliferative capacity of human effector and memory T cells expressing killer cell lectinlike receptor G1 (KLRG1)". Blood 100 (10): 3698–3702. doi:10.1182/blood-2002-02-0657. PMID 12393723. 
  22. ^ a b Ouyang, Q.; W. M. Wagner; D. Voehringer; A. Wikby; T. Klatt; S. Walter; C. A. Muller; H. Pircher; G. Pawelec (2003). "Age-associated accumulation of CMV-specific CD8+ T cells expressing the inhibitory killer cell lectin-like receptor G1 (KLRG1)". Exp Gerontol 38 (8): 911–920. doi:10.1016/S0531-5565(03)00134-7. PMID 12915213. 
  23. ^ a b Naylor, K.; G. Li; A. N. Vallejo; W. W. Lee; K. Koetz; E. Bryl; J. Witkowski; J. Fulbright; C. M. Weyand; J. J. Goronzy (2005). "The influence of age on T cell generation and TCR diversity". J Immunol 174 (11): 7446–7452. doi:10.4049/jimmunol.174.11.7446. PMID 15905594. 
  24. ^ a b Weng, N. P. (2006). "Aging of the Immune System: How Much Can the Adaptive Immune System Adapt?". Immunity 24 (5): 495–499. doi:10.1016/j.immuni.2006.05.001. PMC 2266981. PMID 16713964. 
  25. ^ Suderkotter, C.; H. Kalden (1997). "Aging and the skin immune system". Archives of dermatology 133 (10): 1256–1262. doi:10.1001/archderm.133.10.1256. PMID 9382564.