Immunosenescence

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Immunosenescence ( Latin immunis actually 'tax-free', figuratively 'untouched', 'free', 'pure' and Latin senescere = ' getting old') is the name of the slow deterioration of the immune system in older people. One effect of immunosenescence is an increase in infection-related morbidity and mortality in the elderly.

The term immunosenescence ( Engl. Immunosenescence ) was 1,969 American US from the gerontologist Roy Walford coined.

Even if the following essentially refers to immunosenescence in humans, this phenomenon is not restricted to humans. Most vertebrates , possibly all, are affected.

description

In older people, a number of changes take place in both the innate and adaptive immune defense ("acquired immune system"). These age-related changes lead to a decline in the functionality of the immune system. One speaks of immunosenescence. Immunosenescence can be diagnosed using a number of immunological parameters . The state of the innate and adaptive immune defense in older people correlates directly with the health of those affected. In many cases, however, it is unclear to what extent the dysfunction of the immune system is the cause or the effect.

The age-related degradation of the immune system has direct effects and explains, for example, the increased susceptibility of older people to infectious diseases, diseases that are related to inflammatory processes (such as Alzheimer's or cardiovascular diseases ) and autoimmune diseases . Associated with this are both accelerated aging and increased mortality.

Immunosenescence is a complex developmental process that is more like a restructuring with qualitative changes in parts of the immune system than a general decline in all immune functions.

From an evolutionary point of view, the positive effects of the immune system predominate at a young age, for example to combat pathogens in order to ensure successful reproduction of the organism. Possible negative effects (see also inflammatory aging ) that only occur after the end of the reproductive phase could not be eliminated by evolution through selection .

Changes in the immune system with age

The regression of the thymus begins with sexual maturity . This process is completed between the ages of 40 and 50. Thereafter, T lymphocytes can no longer mature , which means that the immune system is dependent on the existence of the T lymphocytes that have formed up to this point in time. At a young age, the body has a high proportion of naive - that is, non-activated - T lymphocytes, a low proportion of memory cells and hardly any effector cells . In old age, on the other hand, the opposite is true: the effector cells dominate, the memory cells take second place and there are hardly any naive T lymphocytes left. The decrease in T and B lymphocytes with age is known as age-related leukopenia . In contrast, the number of unspecific cytotoxic NK cells increases with age. This reversal of the cell ratios results in changes in the release of cytokines. Interleukin-2 is released significantly less than at a young age, while interleukin-4 and γ-interferon are formed to a greater extent. This in turn causes, among other things, a poorer maturation of the B lymphocytes and a reduced production of antibodies . The changed cytokine milieu, the minimal proliferation of naive T lymphocytes and an altered signal transduction via the T cell receptor (TCR) mean that the immune system can no longer react appropriately when new antigens are presented ( antigen presentation ). B-lymphocytes of type CD19 + are no longer so active in old age to release antibodies after contact with antigens.

In contrast, antigen-presenting cells are still fully functional even in old age.

causes

The immune system is a highly complex defense mechanism of the body in which many factors influence its function. Accordingly, a number of different influencing factors contribute to immunosenescence. Some causes are controversial, which is due, among other things, to the fact that it is often very difficult to determine whether the changes described above at the cellular level are intrinsic for a cell type or are caused by external influences, or whether both are the primary cause. The causality is often unclear. This is especially the case when B lymphocytes interact with T lymphocytes, which is crucial for an effective immune response. If one element is affected, it immediately changes the function of the other.

One of the main causes of the cell biological changes that lead to immunosenescence is seen as the “antigen load” that has acted on the organism in the course of its lifespan. Constant inflammatory processes reduce the number of naive T cells. The repertoire of cells that are able to react to the antigens of pathogens is steadily decreasing.

The human cytomegalovirus (HCMV) is a biomarker that has been linked to immunosenescence. The human immune system does a considerable part of its work in combating or controlling this virus, although the workload increases with age.

According to another theory, in addition to exposure to antigens, diet also plays an important role in the development of immunosenescence. In particular, the undersupply of proteins should contribute to immunosenescence. This is also a starting point for possible therapeutic measures.

Individual evidence

  1. ↑ a b c L. Sedlacek: Telomere length dynamics in subpopulations of peripheral blood lymphocytes in vivo and in vitro. Dissertation, Albert-Ludwigs-Universität Freiburg im Breisgau, 2003.
  2. ^ R. Walford: The immunologic theory of aging. Munksgaard Publishing House, 1969, ISBN 8-716-00008-0
  3. ^ A b S. Vasto and C. Caruso: Immunity & Aging: a new journal looking at aging from an immunological point of view. In: Immun Aging 29, 2004, 1. PMID 15679921 ( Open Access )
  4. ↑ DP Shanley et al .: An evolutionary perspective on the mechanisms of immunosenescence. In: Trends Immunol 30, 2009, pp. 374-381. PMID 19541538 (Review)
  5. ^ JS Goodwin: Decreased immunity and increased morbidity in the elderly. In: Nutr Rev 53, 1995, pp. S41-45. PMID 7644153 (Review)
  6. ^ C. Franceschi et al: The immunology of individuals: the lesson of centenarians. In: Immunol Today 16, 1995, pp. 12-16. PMID 7880382 (Review)
  7. ^ IC Roberts-Thomson et al: Aging, immune response, and mortality. In: The Lancet 2, 1974, pp. 368-370. PMID 4136513
  8. ↑ SJ Wayne et al.: Cell-mediated immunity as a predictor of morbidity and mortality in subjects over 60. In: J Gerontol 45, 1990, pp. M45-48. PMID 2313042
  9. ↑ HS Gill et al .: Enhancement of immunity in the elderly by dietary supplementation with the probiotic Bifidobacterium lactis HN019. In: Am J Clin Nutr 74, 2001, pp. 833-839. PMID 11722966
  10. ↑ A. Globerson and RB Effros: Aging of lymphocytes and lymphocytes in the aged. In: Immunol Today 21, 2000, pp. 515-521. PMID 11071531 (Review)
  11. ↑ C. Franceschi et al .: Inflamm-aging. An evolutionary perspective on immunosenescence. In: Ann NY Acad Sci 908, 2000, pp. 244-254. PMID 10911963 (Review)
  12. ^ P. Sansoni et al .: Lymphocyte subsets and natural killer cell activity in healthy old people and centenarians. In: Blood 82, 1993, pp. 2767-2773. PMID 8219229
  13. ↑ RB Effros and G. Pawelec: Replicative senescence of T cells: does the Hayflick Limit lead to immune exhaustion? In: Immunol Today 18, 1997, pp. 450-454. PMID 9293162
  14. ↑ FF Fagnoni include: Shortage of circulating naive CD8 (+) T cells Provides new insights on aging in immunodeficiency. In: Blood 95, 2000, pp. 2860-2868. PMID 10779432
  15. ↑ L. Nagelkerken et al .: Age-related changes in lymphokine production related to a decreased number of CD45RBhi CD4 + T cells. In: Eur J Immunol 21, 1991, pp. 273-281. PMID 1671835
  16. ^ F. Thalhammer: Vaccination in old age. (PDF; 1.3 MB) In: Österreichische Ärztezeitung November 2008
  17. ↑ M. Utsuyama et al: Influence of age on the signal transduction of T cells in mice. In: Int Immunol 5, 1993, pp. 1177-1182. PMID 8241056
  18. ^ RA Miller: The aging immune system: primer and prospectus. In: Science 273, 1996, pp. 70-74. PMID 8658199
  19. ↑ RJ Hodes: Aging and the immune system. In: Immunol Rev 160, 1997, pp. 5-8. PMID 9476660
  20. ↑ G. Pawelec et al: T cells and aging. In: Front Biosci 7, 2002, pp. D1056-d1183. PMID 11991846
  21. ↑ a b C. Caruso et al .: Mechanisms of immunosenescence In: Immun Aging 6, 2009, 10. doi : 10.1186 / 1742-4933-6-10 PMID 19624841 ( Open Access )
  22. ↑ A. Larbi et al .: Aging of the immune system as a prognostic factor for human longevity. In: Physiology 23, 2008, pp. 64-74. PMID 18400689 (Review)
  23. ↑ H. Bruunsgaard: The clinical impact of systemic low-level inflammation in elderly populations. With special reference to cardiovascular disease, dementia and mortality. In: Dan Med Bull 53, 2006, pp. 285-309. PMID 17092450
  24. ↑ F. Licastro include: Innate immunity and inflammation in aging: a key for understanding age-related diseases. In: Immun Aging 2, 2005, 8th PMID 15904534 ( Open Access )
  25. ↑ FF Fagnoni include: Shortage of circulating naive CD8 (+) T cells Provides new insights on aging in immunodeficiency. In: Blood 95, 2000, pp. 2860-2868. PMID 10779432
  26. ↑ E. Derhovanessian et al.: Biomarkers of human immunosenescence: impact of cytomegalovirus infection. In: Curr Opin Immunol 21, 2009, pp. 440-445. PMID 19535233 (Review)
  27. ↑ G. Pawelec, A. Larbi, E. Derhovanessian: Senescence of the human immune system. In: J. Comp. Pathol. 142 Suppl 1, 2010, pp. S39-S44 PMID 19897208 (review).
  28. ↑ G. Pawelec: Cytomegalovirus and human immunosenescence. In: Rev Med Virol 19, 2009, pp. 47-56. PMID 19035529 (Review)
  29. ↑ S. Koch et al.: Cytomegalovirus infection: a driving force in human T cell immunosenescence. In: Ann NY Acad Sci 1114, 2007, pp. 23-35. PMID 17986574 (Review)
  30. ↑ BM Lesourd and S. Meaume: Cell mediated immunity changes in aging: relative importance of cell subpopulation switches and of nutritional factors. In: Immunol Lett 40, 1994, pp 235-242. PMID 7959893 (Review)
  31. ↑ T. Makinodan: Patterns of age-related immunologic changes. In: Nutr Rev 53, 1995, pp. S27-31. PMID 7644150 (Review)
  32. ^ BM Lesourd et al .: The role of nutrition in immunity in the aged. In: Nutr Rev 56, 1998, pp. S113-125. PMID 9481132 (Review)
  33. ↑ BM Lesourd: Protein undernutrition as the major cause of decreased immune function in the elderly: clinical and functional implications. In: Nutr Rev 53, 1995, pp. S86-92. PMID 7644161
  34. ^ BM Lesourd: Nutrition: a major factor influencing immunity in the elderly. In: J Nutr Health Aging 8, 2004, pp. 28-37. PMID 14730365 (Review)

further reading

  • RJ Hodes: Molecular alterations in the aging immune system. In: The Journal of experimental medicine. Volume 182, Number 1, July 1995, pp. 1-3, PMID 7540645 , PMC 2192083 (free full text).
  • Donald B. Palmer: The Effect of Age on Thymic Function. In: Frontiers in Immunology. 4, 2013, S., doi : 10.3389 / fimmu.2013.00316 . (Review)

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