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Imunossenescência
Aluna: Bárbara Hamaguchi
Orientação: Prof. Dr. Michelangelo Juvenale
Trabalho de Conclusão de Curso – Biomedicina/2015
2040
1,3 Bilhões
de idosos
OMS, 2015.
14%da população
mundial
ONU, 2014.
fatores
MUDARAM
Alguns
Viver mais, é diferente
de viver melhor
Objetivo
Descrever os efeitos do envelhecimento
sobre as células sistema imunológico
Método
Revisão de literatura em bases de dados e livros.
Imunossenescência; involução tímica; imunidade
adaptativa; inata; inflammaging.
Descritores
Imunossenescência
Involução
Tímica
Adaptação ou deterioramento?
HAYNES et al., 2000.
GAPS
IMUNOLÓGICOS
Foxn1
T naïve
Soma descartável
Evitar autoimunidade
Mais memória
“Ajuste fino”
?
(ARONSON, 1991)
(GEORGE e RITTER, 1996)
(DOWLING e HODGKIN, 2009)
(O’LEARY e HALLGREN, 2009)
T CD8+ CD27- CD28- /CD45+
CMV
CD56
Anergia
Resistência à
apoptose
(LOONEY et al., 1999; MCLEOD, 2001; PAWELEC et al., 2006; WENG, AKBAR e GORONZY, 2009)
CD4:CD8 < 1
Linfócitos B
Proteína E47
Aicda
AID
Switch de
classe
(FRASCA et al., 2007; LANDIN et al., 2011)
(BEERMAN et al., 2010; ROSSI et al., 2005)
QUIMIOTAXIA
PI3K
SAPEY et al., 2014. A relação da
Neutrófilos
(Quinase fosfatidil-inositol 3)
Neutrófilos
Fagocitose
NET
EROs
BRUBAKER et al., 2013; BUTCHER et al., 2004; TSENG et al., 2012
Macrófagos/monócitos
In vivo
Ex vivo
IL-6
TNF-α
IL -1β
CD16+CD14+
(GOMEZ et al., 2009; RENSHAW et al., 2002; SEIDLER et al., 2010)
Células NK
Células TCD8+
(LOPES-VERGÈS et al., 2011; SUN et al., 2011)
“Inflammaging”
Immune Risk Profile (IRP)
TNF-α
IL-8
(WIKBY et al., 1994; 1998; 2002; 2006)
De que maneira os
são diferentes?
Centenários saudáveis
(DE MARTINIS et al., 2005; FRANCESCHI et al., 2000)
Considerações finais
Adaptação Imunossenescência
ARONSON, M. Hypothesis: involution of the thymus with aging--programmed and beneficial. Thymus, v. 18, n. 1, p. 7-13, 1991.
BEERMAN, I. et al. Functionally distinct hematopoietic stem cells modulate hematopoietic lineage potential during aging by a
mechanism of clonal expansion. Proceedings of the National Academy of Sciences, v. 107, n. 12, p. 5465-5470, 2010.
BRUBAKER, A. L. et al. Reduced neutrophil chemotaxis and infiltration contributes to delayed resolution of cutaneous wound
infection with advanced age. The Journal of Immunology, v. 190, n. 4, p. 1746-1756, 2013.
BUTCHER, S. K. et al. Neutrophil Ageing and Immunosenescence. , 4, 41-55. NeuroImmune Biology, v. 4, p. 41-55, 2004.
DE MARTINIS, M. et al. Inflamm-ageing and lifelong antigenic load as major determinants of ageing rate and longevity. FEBS
letters, v. 579, n. 10, p. 2035-2039, 2005.
DOWLING, M. R.; HODGKIN, P. D. Why does the thymus involute? A selection-based hypothesis. Trends in Immunology, v.
30, n. 7, p. 295-300, 2009.
FRANCESCHI, C. et al. The network and the remodeling theories of aging: historical background and new perspectives.
Experimental gerontology, v. 35, n. 6, p. 879-896, 2000.
Referências
FRASCA, D. et al. Tristetraprolin, a negative regulator of mRNA stability, is increased in old B cells and is involved in the
degradation of E47 mRNA. The Journal of Immunology, 179(2), 918-927., v. 179, n. 2, p. 918-927, 2007.
GEORGE, A. J.; RITTER, M. A. Thymic involution with ageing: obsolescence or good housekeeping? Immunology today, v. 17,
n. 6, p. 267-272, 1996.
GOMEZ, C. R. et al. Comparison of the effects of aging and IL-6 on the hepatic inflammatory response in two models of
systemic injury: scald injury versus ip LPS administration. Shock (Augusta, Ga.), v. 31, n. 2, p. 178-184, 2009.
HAYNES, B. F. et al. The human thymus during aging. Immunologic research, v. 22, n. 2-3, p. 253-261, 2000.
LANDIN, A. M. et al. E47 retroviral rescue of intrinsic B-cell defects in senescent mice. Aging cell, v. 10, n. 2, p. 327-337, 2011.
LOONEY, R. J. et al. Role of cytomegalovirus in the T cell changes seen in elderly individuals. Clinical Immunology, v. 90, n. 2,
p. 213-219, 1999.
LOPEZ-VERGÈS, S. et al. LExpansion of a unique CD57+ NKG2Chi natural killer cell subset during acute human
cytomegalovirus infection. Proceedings of the National Academy of Sciences, v. 108, n. 36, p. 14725-14732, 2011.
MCLEOD, J. D. Apoptotic capability in ageing T cells. Mechanisms of ageing and development, v. 121, n. 1, p. 151-159, 2001.
O'LEARY, J. J.; HALLGREN, H. M. Aging and lymphocyte function: a model for testing gerontologic hypotheses of aging in man.
Archives of gerontology and geriatrics, v. 12, n. 2, p. 199-218, 1991.
O'LEARY, J. J.; HALLGREN, H. M. Aging and lymphocyte function: a model for testing gerontologic hypotheses of aging in man.
Archives of gerontology and geriatrics, v. 12, n. 2, p. 199-218, 1991.
RENSHAW, M. et al. Cutting edge: impaired Toll-like receptor expression and function in aging. The Journal of Immunology, v.
169, n. 9, p. 4697-4701, 2002.
ROSSI, D. J. et al. Cell intrinsic alterations underlie hematopoietic stem cell aging. Proceedings of the National Academy of
Sciences of the United States of America, v. 102, n. 26, p. 9194-9199, 2005.
SAPEY, E. et al. (2014). Phosphoinositide 3-kinase inhibition restores neutrophil accuracy in the elderly: toward targeted
treatments for immunosenescence. Blood, v. 123, n. 2, p. 239-248, 2014.
SEIDLER, S. et al. Age-dependent alterations of monocyte subsets and monocyte-related chemokine pathways in healthy
adults.. BMC immunology, v. 11, n. 1, p. 30, 2010.
SUN, J. C. et al. Homeostatic proliferation generates long-lived natural killer cells that respond against viral infection. The
Journal of experimental medicine, v. 208, n. 2, p. 357-368, 2011.
TSENG, C. W. et al. Innate immune dysfunctions in aged mice facilitate the systemic dissemination of methicillin-resistant S.
aureus. PloS one, v. 7, n. 7, p. e41454., 2012.
WENG, N.P.; AKBAR, A. N.; GORONZY, J. CD28− T cells: their role in the age-associated decline of immune function. Trends in
immunology, v. 30, n. 7, p. 306-312, 2009.
WIKBY, A. et al. Age-related changes in immune parameters in a very old population of Swedish people: a longitudinal study.
Experimental gerontology, v. 29, n. 5, p. 531-541, 1994
WIKBY, A. et al. Changes in CD8 and CD4 lymphocyte subsets, T cell proliferation responses and non-survival in the very old:
the Swedish longitudinal OCTO-immune study. Mechanisms of ageing and development, v. 102, n. 2, p. 187-198, 1998.
WIKBY, A. et al. Expansions of peripheral blood CD8 T-lymphocyte subpopulations and an association with cytomegalovirus
seropositivity in the elderly: the Swedish NONA immune study. Experimental gerontology, v. 37, n. 2, p. 445-453, 2002.
WIKBY, A. et al. The immune risk phenotype is associated with IL-6 in the terminal decline stage: findings from the Swedish
NONA immune longitudinal study of very late life functioning.. Mechanisms of ageing and development, v. 127, n. 8, p. 695-
704, 2006.

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Imunossenescência

  • 1. Imunossenescência Aluna: Bárbara Hamaguchi Orientação: Prof. Dr. Michelangelo Juvenale Trabalho de Conclusão de Curso – Biomedicina/2015
  • 5. Viver mais, é diferente de viver melhor
  • 6. Objetivo Descrever os efeitos do envelhecimento sobre as células sistema imunológico
  • 7. Método Revisão de literatura em bases de dados e livros. Imunossenescência; involução tímica; imunidade adaptativa; inata; inflammaging. Descritores
  • 10. HAYNES et al., 2000. GAPS IMUNOLÓGICOS Foxn1 T naïve
  • 11. Soma descartável Evitar autoimunidade Mais memória “Ajuste fino” ? (ARONSON, 1991) (GEORGE e RITTER, 1996) (DOWLING e HODGKIN, 2009) (O’LEARY e HALLGREN, 2009)
  • 12. T CD8+ CD27- CD28- /CD45+ CMV CD56 Anergia Resistência à apoptose (LOONEY et al., 1999; MCLEOD, 2001; PAWELEC et al., 2006; WENG, AKBAR e GORONZY, 2009)
  • 14. Linfócitos B Proteína E47 Aicda AID Switch de classe (FRASCA et al., 2007; LANDIN et al., 2011)
  • 15. (BEERMAN et al., 2010; ROSSI et al., 2005)
  • 16. QUIMIOTAXIA PI3K SAPEY et al., 2014. A relação da Neutrófilos (Quinase fosfatidil-inositol 3)
  • 17. Neutrófilos Fagocitose NET EROs BRUBAKER et al., 2013; BUTCHER et al., 2004; TSENG et al., 2012
  • 18. Macrófagos/monócitos In vivo Ex vivo IL-6 TNF-α IL -1β CD16+CD14+ (GOMEZ et al., 2009; RENSHAW et al., 2002; SEIDLER et al., 2010)
  • 19. Células NK Células TCD8+ (LOPES-VERGÈS et al., 2011; SUN et al., 2011)
  • 20. “Inflammaging” Immune Risk Profile (IRP) TNF-α IL-8 (WIKBY et al., 1994; 1998; 2002; 2006)
  • 21. De que maneira os são diferentes? Centenários saudáveis (DE MARTINIS et al., 2005; FRANCESCHI et al., 2000)
  • 23. ARONSON, M. Hypothesis: involution of the thymus with aging--programmed and beneficial. Thymus, v. 18, n. 1, p. 7-13, 1991. BEERMAN, I. et al. Functionally distinct hematopoietic stem cells modulate hematopoietic lineage potential during aging by a mechanism of clonal expansion. Proceedings of the National Academy of Sciences, v. 107, n. 12, p. 5465-5470, 2010. BRUBAKER, A. L. et al. Reduced neutrophil chemotaxis and infiltration contributes to delayed resolution of cutaneous wound infection with advanced age. The Journal of Immunology, v. 190, n. 4, p. 1746-1756, 2013. BUTCHER, S. K. et al. Neutrophil Ageing and Immunosenescence. , 4, 41-55. NeuroImmune Biology, v. 4, p. 41-55, 2004. DE MARTINIS, M. et al. Inflamm-ageing and lifelong antigenic load as major determinants of ageing rate and longevity. FEBS letters, v. 579, n. 10, p. 2035-2039, 2005. DOWLING, M. R.; HODGKIN, P. D. Why does the thymus involute? A selection-based hypothesis. Trends in Immunology, v. 30, n. 7, p. 295-300, 2009. FRANCESCHI, C. et al. The network and the remodeling theories of aging: historical background and new perspectives. Experimental gerontology, v. 35, n. 6, p. 879-896, 2000. Referências
  • 24. FRASCA, D. et al. Tristetraprolin, a negative regulator of mRNA stability, is increased in old B cells and is involved in the degradation of E47 mRNA. The Journal of Immunology, 179(2), 918-927., v. 179, n. 2, p. 918-927, 2007. GEORGE, A. J.; RITTER, M. A. Thymic involution with ageing: obsolescence or good housekeeping? Immunology today, v. 17, n. 6, p. 267-272, 1996. GOMEZ, C. R. et al. Comparison of the effects of aging and IL-6 on the hepatic inflammatory response in two models of systemic injury: scald injury versus ip LPS administration. Shock (Augusta, Ga.), v. 31, n. 2, p. 178-184, 2009. HAYNES, B. F. et al. The human thymus during aging. Immunologic research, v. 22, n. 2-3, p. 253-261, 2000. LANDIN, A. M. et al. E47 retroviral rescue of intrinsic B-cell defects in senescent mice. Aging cell, v. 10, n. 2, p. 327-337, 2011. LOONEY, R. J. et al. Role of cytomegalovirus in the T cell changes seen in elderly individuals. Clinical Immunology, v. 90, n. 2, p. 213-219, 1999. LOPEZ-VERGÈS, S. et al. LExpansion of a unique CD57+ NKG2Chi natural killer cell subset during acute human cytomegalovirus infection. Proceedings of the National Academy of Sciences, v. 108, n. 36, p. 14725-14732, 2011. MCLEOD, J. D. Apoptotic capability in ageing T cells. Mechanisms of ageing and development, v. 121, n. 1, p. 151-159, 2001. O'LEARY, J. J.; HALLGREN, H. M. Aging and lymphocyte function: a model for testing gerontologic hypotheses of aging in man. Archives of gerontology and geriatrics, v. 12, n. 2, p. 199-218, 1991.
  • 25. O'LEARY, J. J.; HALLGREN, H. M. Aging and lymphocyte function: a model for testing gerontologic hypotheses of aging in man. Archives of gerontology and geriatrics, v. 12, n. 2, p. 199-218, 1991. RENSHAW, M. et al. Cutting edge: impaired Toll-like receptor expression and function in aging. The Journal of Immunology, v. 169, n. 9, p. 4697-4701, 2002. ROSSI, D. J. et al. Cell intrinsic alterations underlie hematopoietic stem cell aging. Proceedings of the National Academy of Sciences of the United States of America, v. 102, n. 26, p. 9194-9199, 2005. SAPEY, E. et al. (2014). Phosphoinositide 3-kinase inhibition restores neutrophil accuracy in the elderly: toward targeted treatments for immunosenescence. Blood, v. 123, n. 2, p. 239-248, 2014. SEIDLER, S. et al. Age-dependent alterations of monocyte subsets and monocyte-related chemokine pathways in healthy adults.. BMC immunology, v. 11, n. 1, p. 30, 2010. SUN, J. C. et al. Homeostatic proliferation generates long-lived natural killer cells that respond against viral infection. The Journal of experimental medicine, v. 208, n. 2, p. 357-368, 2011. TSENG, C. W. et al. Innate immune dysfunctions in aged mice facilitate the systemic dissemination of methicillin-resistant S. aureus. PloS one, v. 7, n. 7, p. e41454., 2012. WENG, N.P.; AKBAR, A. N.; GORONZY, J. CD28− T cells: their role in the age-associated decline of immune function. Trends in immunology, v. 30, n. 7, p. 306-312, 2009.
  • 26. WIKBY, A. et al. Age-related changes in immune parameters in a very old population of Swedish people: a longitudinal study. Experimental gerontology, v. 29, n. 5, p. 531-541, 1994 WIKBY, A. et al. Changes in CD8 and CD4 lymphocyte subsets, T cell proliferation responses and non-survival in the very old: the Swedish longitudinal OCTO-immune study. Mechanisms of ageing and development, v. 102, n. 2, p. 187-198, 1998. WIKBY, A. et al. Expansions of peripheral blood CD8 T-lymphocyte subpopulations and an association with cytomegalovirus seropositivity in the elderly: the Swedish NONA immune study. Experimental gerontology, v. 37, n. 2, p. 445-453, 2002. WIKBY, A. et al. The immune risk phenotype is associated with IL-6 in the terminal decline stage: findings from the Swedish NONA immune longitudinal study of very late life functioning.. Mechanisms of ageing and development, v. 127, n. 8, p. 695- 704, 2006.