Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
권호 표지
DOI QR코드

DOI QR Code

Aging of Immune System

면역 반응체계의 노화

  • Received : 2019.07.23
  • Accepted : 2019.07.25
  • Published : 2019.07.30
Download PDF
⟨ Previous Next ⟩

Abstract

Immune system provides defense integrity of body against external invaders. In order to accomplish the important defending role immune system is composed of many different components which are regenerated continuously during lifespan. The key components are professional killing cells such as macrophage, neutrophil, natural killer cell, and cytotoxic T cell and professional blocking molecule, antibody, which is produced by plasma cell, the terminal differentiated B cell. Immune response is orchestrated harmoniously by all these components mediated through antigen presenting cells such as dendritic cells. Immune responses can be divided into two ways: innate immune response and adaptive immune response depending on induction mechanism. Aging is a broad spectrum of physiological changes. Likewise other physiological changes, the immune components and responses are wane as aging is progressing. Immune responses become decline and dysregulating, which is called immunosenescense. Immune components of both innate and adaptive immune response are affected as aging progresses leading to increased vulnerability to infectious diseases. Numbers of immune cells and amounts of soluble immune factors were decreased in aged animal models and human and also functional and structural alterations in immune system were reduced and declined. Cellular intrinsic changes were discovered as well. Recent researches focusing on aging have been enormously growing. Many advanced tools were developed to bisect aging process in multi-directions including immune system area. This review will provide a broad overview of aging-associated changes of key components of immunity.

노화는 광범위한 생리 변화이다. 노화가 진행됨에 따라 면역반응은 쇠퇴하고 조절장애가 나타나는데 이를 포괄적 의미로 immunosenescense라고 정의한다. 내재면역반응과 적응면역 반응 모두의 면역 성분은 노화가 진행됨에 따라 영향을 받아 감염성 질병에 대한 취약성이 증가하게 된다. 노화된 동물 모델과 인간에서 면역 세포의 수와 용해성 면역 인자의 양이 줄어 들었고, 면역체계의 기능이 감소하였고, 구조적인 변형과 퇴화가 나타났다. 또한, 세포 내 신호분자와 같은 내재적 변화도 발견되었다. 최근 노화와 관련된 연구는 급격히 증가하였고, 면역체계 영역을 포함하여 다양한 방향으로 노화현상을 분석하는 진보된 기술들이 개발되고 있다. 이 총설은 면역의 주요 구성 요소의 노화 관련 변화에 대한 광범위한 개요를 제공하고자 하였다.

Keywords

SMGHBM_2019_v29n7_817_f0001.png 이미지

Fig. 1. Composition of immune system.

SMGHBM_2019_v29n7_817_f0002.png 이미지

Fig. 2. Changes of Immune responses from young to elderly people.

SMGHBM_2019_v29n7_817_f0003.png 이미지

Fig. 3. Schematic graphs of lymphocyte population changes as the aging process progresses.

Table 1. Age-related functional changes of macrophage

SMGHBM_2019_v29n7_817_t0001.png 이미지

References

  1. Bailey, K. L., Smith, L. M., Heires, A. J., Katafiasz, D. M., Romberger, D. J. and LeVan, T. D. 2018. Aging leads to dysfunctional innate immune responses to TLR2 and TLR4 agonists. Aging Clin. Exp. Res. doi:10.1007/s40520-018-1064-0.
  2. Becklund, B. R., Purton, J. F., Ramsey, C., Favre, S., Vogt. T. K., Martin, C. E., Spasova, D. S., Sarkisyan, G., LeRoy, E., Tan, J. T., Wahlus, H., Bondi-Boyd, B., Luther, S. A. and Surh, C. D. 2016. The aged lymphoid tissue environment fails to support naïve T cell homeostasis. Sci. Rep. 6, 30842. https://doi.org/10.1038/srep30842
  3. Chougnet, C. A., Thacker, R. I., Shehata, H. M., Hennies, C. M., Lehn, M. A., Lages, C. S. and Janssen, E. M. 2015. Loss of phagocytic and antigen cross-presenting capacity in aging dendritic cells is associated with mitochondrial dysfunction. J. Immunol. 195, 2624-2632. https://doi.org/10.4049/jimmunol.1501006
  4. Derhovanessian, E., Larbi, A. and Pawelec, G. 2009. Biomarkers of human immunosenescence: impact of Cytomegalovirus infection. Curr. Opin. Immunol. 21, 440-445. https://doi.org/10.1016/j.coi.2009.05.012
  5. Dunn-Walters, D., Townsend, C., Sinclair, E. and Stewart, A. 2018. Immunoglobulin gene analysis as a tool for investigating human immune responses. Immunol. Rev. 284, 132-147. https://doi.org/10.1111/imr.12659
  6. Frasca, D. 2018. Senescent B cells in aging and age-related diseases: Their role in the regulation of antibody responses. Exp. Gerontol. 107, 55-58. https://doi.org/10.1016/j.exger.2017.07.002
  7. Fulop, T., Larbi, A., Douziech, N., Fortin, C., Guerard, K. P., Lesur, O., Khalil, A. and Dupuis, G. 2004. Signal transduction and functional changes in neutrophils with aging. Aging Cell. 3, 217-226. https://doi.org/10.1111/j.1474-9728.2004.00110.x
  8. Fulop, T., Larbi, A. and Pawelec, G. 2013. Human T cell aging and the impact of persistent viral infections. Front. Immunol. 4, 271. https://doi.org/10.3389/fimmu.2013.00271
  9. Gibson, K. L., Wu, Y. C., Barnett, Y., Duggan, O., Vaughan, R., Kondeatis, E., Nilsson, B. O., Wikby, A., Kipling, D. and Dunn-Walters, D. K. 2009. B-cell diversity decreases in old age and is correlated with poor health status. Aging Cell. 8, 18-25. https://doi.org/10.1111/j.1474-9726.2008.00443.x
  10. Hao, Y., O'Neill, P., Naradikian, M. S., Scholz, J. L. and Cancro, M. P. 2011. A B-cell subset uniquely responsive to innate stimuli accumulates in aged mice. Blood 118, 1294-1304. https://doi.org/10.1182/blood-2011-01-330530
  11. Kogut, I., Scholz, J. L., Cancro, M. P. and Cambier, J. C. 2012. B cell maintenance and function in aging. Semin. Immunol. 24, 342-349. https://doi.org/10.1016/j.smim.2012.04.004
  12. Labrie, J. E. 3rd, Sah, A. P., Allman, D. M., Cancro, M. P. and Gerstein, R. M. 2004. Bone marrow microenvironmental changes underlie reduced RAG-mediated recombination and B cell generation in aged mice. J. Exp. Med. 200, 411-423. https://doi.org/10.1084/jem.20040845
  13. Lopez-Otín, C., Blasco, M. A., Partridge, L., Serrano, M. and Kroemer, G. 2013. The hallmarks of aging. Cell 153, 1194-1217. https://doi.org/10.1016/j.cell.2013.05.039
  14. Manser, A. R. and Uhrberg, M. 2016. Age-related changes in natural killer cell repertoires: impact on NK cell function and immune surveillance. Cancer Immunol. Immunother. 65, 417-426. https://doi.org/10.1007/s00262-015-1750-0
  15. Maue, A. C., Yager, E. J., Swain, S. L., Woodland, D. L., Blackman, M. A. and Haynes, L. 2009 T-cell immunosenescence: lessons learned from mouse models of aging. Trends Immunol. 30, 301-305. https://doi.org/10.1016/j.it.2009.04.007
  16. Muller, L., Pawelec, G. and Derhovanessian, E. 2013. The immune system during aging. In: Calder P, Yaqoob P (eds) Diet, immunity and inflammation. Woodhead Publishing. Oxford, 631-651.
  17. Muller, L., Di Benedetto, S. and Pawelec, G. 2019. The immune system and its dysregulation with aging. Subcell. Biochem. 91, 21-43. https://doi.org/10.1007/978-981-13-3681-2_2
  18. Muller-Sieburg, C. E., Sieburg, H. B., Bernitz, J. M. and Cattarossi, G. 2012. Stem cell heterogeneity: implications for aging and regenerative medicine. Blood 119, 3900-3907. https://doi.org/10.1182/blood-2011-12-376749
  19. Murasko, D. M. and Jiang, J. 2005. Response of aged mice to primary virus infections. Immunol. Rev. 205, 285-296. https://doi.org/10.1111/j.0105-2896.2005.00273.x
  20. Nikolich-Zugich, J. 2018. The twilight of immunity: emerging concepts in aging of the immune system. Nat. Immunol. 19, 10-19. https://doi.org/10.1038/s41590-017-0006-x
  21. Olsson, J., Wikby, A., Johansson, B., Löfgren, S., Nilsson, B. O. and Ferguson, F. G. 2000. Age-related change in peripheral blood T-lymphocyte subpopulations and cytomegalovirus infection in the very old: the Swedish longitudinal OCTO immune study. Mech. Ageing Dev. 121, 187-201. https://doi.org/10.1016/S0047-6374(00)00210-4
  22. Paganelli, R., Quinti, I., Fagiolo, U., Cossarizza, A., Ortolani, C., Guerra, E., Sansoni, P., Pucillo, L. P., Scala, E. and Cozzi, E., et al. 1992. Changes in circulating B cells and immunoglobulin classes and subclasses in a healthy aged population. Clin. Exp. Immunol. 90, 351-354. https://doi.org/10.1111/j.1365-2249.1992.tb07954.x
  23. Pawelec, G. 2014. Immunosenenescence: role of cytomegalovirus. Exp. Gerontol. 54, 1-5. https://doi.org/10.1016/j.exger.2013.11.010
  24. Pawelec, G. 2018. Immune parameters associated with mortality in the elderly are context-dependent: lessons from Sweden, Holland and Belgium. Biogerontology 19, 537-545. https://doi.org/10.1007/s10522-017-9739-z
  25. Pawelec, G., Solana, R., Remarque, E. and Mariani, E. 1998. Impact of aging on innate immunity. J. Leukoc. Biol. 64, 703-712. https://doi.org/10.1002/jlb.64.6.703
  26. Plowden, J., Renshaw-Hoelscher, M., Engleman, C., Katz, J. and Sambhara, S. 2004. Innate immunity in aging: impact on macrophage function. Aging Cell. 3, 161-167. https://doi.org/10.1111/j.1474-9728.2004.00102.x
  27. Rafael, S., Graham, P. and Raquel, T. 2006. Aging and innate immunity. Immunity 24, 491-494. https://doi.org/10.1016/j.immuni.2006.05.003
  28. Rubtsov, A. V., Rubtsova, K., Fischer, A., Meehan, R. T., Gillis, J. Z., Kappler, J. W. and Marrack, P. 2011. Toll-like receptor 7 (TLR7)-driven accumulation of a novel $CD11c^+$ B-cell population is important for the development of autoimmunity. Blood 118, 1305-1315. https://doi.org/10.1182/blood-2011-01-331462
  29. Rubtsova, K., Rubtsov, A. V., Cancro, M. P. and Marrack, P. 2015. Age-associated B Cells: A T-bet-dependent effector with roles in protective and pathogenic immunity. J. Immunol. 195, 1933-1937. https://doi.org/10.4049/jimmunol.1501209
  30. Sansoni, P., Vescovini, R., Fagnoni, F., Biasini, C., Zanni, F., Zanlari, L., Telera, A., Lucchini, G., Passeri, G., Monti, D., Franceschi, C. and Passeri, M. 2008. The immune system in extreme longevity. Exp. Gerontol. 43, 61-65. https://doi.org/10.1016/j.exger.2007.06.008
  31. Shaw, A. C., Panda, A., Joshi, S. R., Qian, F., Allore, H. G. and Montgomery, R. R. 2011. Dysregulation of human Toll-like receptor function in aging. Ageing Res. Rev. 10, 346-353. https://doi.org/10.1016/j.arr.2010.10.007
  32. Scholz, J. L., Diaz, A., Riley, R. L., Cancro, M. P. and Frasca, D. 2013. A comparative review of aging and B cell function in mice and humans. Curr. Opin. Immunol. 25, 504-510. https://doi.org/10.1016/j.coi.2013.07.006
  33. Shahaf, G., Johnson, K. and Mehr, R. 2006. B cell development in aging mice: lessons from mathematical modeling. Int. Immunol. 18, 31-39. https://doi.org/10.1093/intimm/dxh346
  34. Solana, R., Pawelec, G. and Tarazona, R. 2006. Aging and innate immunity. Immunity 24, 491-494. https://doi.org/10.1016/j.immuni.2006.05.003
  35. Strindhall, J., Skog, M., Ernerudh, J., Bengner, M., Löfgren, S., Matussek, A., Nilsson, B. O. and Wikby, A. 2013. The inverted CD4/CD8 ratio and associated parameters in 66-year-old individuals: the Swedish HEXA immune study. Age (Dordr) 35, 985-991. https://doi.org/10.1007/s11357-012-9400-3
  36. Swain, S. L., Kugler-Umana, O., Kuang, Y. and Zhang, W. 2017. The properties of the unique age-associated B cell subset reveal a shift in strategy of immune response with age. Cell Immunol. 321, 52-60. https://doi.org/10.1016/j.cellimm.2017.05.009
  37. Tabibian-Keissar, H., Hazanov, L., Schiby, G., Rosenthal, N., Rakovsky, A., Michaeli, M., Shahaf, G. L., Pickman, Y., Rosenblatt, K., Melamed, D., Dunn-Walters, D., Mehr, R. and Barshack, I. 2016. Aging affects B-cell antigen receptor repertoire diversity in primary and secondary lymphoid tissues. Eur. J. Immunol. 46, 480-492. https://doi.org/10.1002/eji.201545586
  38. Tsay, G. J. and Zouali, M. 2018. The interplay between innate-like B cells and other cell types in autoimmunity. Front. Immunol. 9, 1064. https://doi.org/10.3389/fimmu.2018.01064
  39. Wikby, A., Olsson, J., Lofgren, S., Nilsson, B. O. and Ferguson, F. G. 2002. Expansions of peripheral blood CD8 T-lymphocyte subpopulations and an association with cytomegalovirus seropositivity in the elderly: the Swedish NONA immune study. Exp. Gerontol. 37, 445-453. https://doi.org/10.1016/S0531-5565(01)00212-1
  40. Wikby, A., Ferguson, F., Forsey, R., Thompson, J., Strindhall, J., Lofgren, S., Nilsson, B. O., Ernerudh, J., Pawelec, G. and Johansson, B. 2005. An immune risk phenotype, cognitive impairment, and survival in very late life: impact of allostatic load in Swedish octogenarian and nonagenarian humans. J. Gerontol. A Biol. Sci. Med. Sci. 60, 556-565. https://doi.org/10.1093/gerona/60.5.556
  41. Yanes, R. E., Gustafson, C. E., Weyand, C. M. and Goronzy, J. J. 2017. Lymphocyte generation and population homeostasis throughout life. Semin. Hematol. 54, 33-38. https://doi.org/10.1053/j.seminhematol.2016.10.003