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The Immune Response to Influenza Infection

Effect of ageing on the immune system

Immunosenescence is the global term for age-related changes that are associated with an increased risk of infection in older adults. A gradual shift with ageing from predominantly naive T cells to increasing proportions of memory T cells reflects the multiple immune responses that are mounted throughout life. Thymic involution and the loss of naive T cells with ageing will ultimately exhaust the capacity of the immune system to respond to new antigens and may thus result in an increased risk of contracting infections, including influenza, as a hallmark of immunosenescence. Recent studies suggest that although early immune responses to influenza may be similar in young and older adults, the ability to maintain or expand memory helper T cells that can respond to influenza challenge declines with ageing. 17 x I Kang, MS Hong, H Nolasco, et al.. Age-associated change in the frequency of memory CD4+ T cells impairs long term CD4+ T cell responses to influenza vaccine. J Immunol 173 (2004) (673 - 681) Although mucosal and systemic antibodies are the first line of defence of the adaptive immune response, just increased levels of mucosal antibodies to influenza do not necessarily translate into clinically meaningful differences in protection against influenza.

Costimulatory molecules, the regulation of cytokine production by both helper T cells and CTLs, and cytolytic mediators from both natural killer cells and CTLs, also have critical roles in the response to influenza infection and recovery from illness. The age-related loss of CD28 expression on CTLs is associated with replicative senescence, growth arrest, increased production of several pro-inflammatory cytokines, resistance to apoptosis, 18 x RB Effros, M Dagarag, HF Valenzuela. In vitro senescence of immune cells. Exp Gerontol 38 (2003) (1243 - 1249) Crossref. and the loss of CD28-mediated costimulation required for optimal stimulation of CTLs. 19, x RB Effros, N Boucher, V Porter, et al.. Decline in CD28+ T cells in centenarians and in long-term T cell cultures: a possible cause for both in vivo and in vitro immunosenescence. Exp Gerontol 29 (1994) (601 - 609) Crossref. 20 x CR Engwerda, BS Handwerger, BS Fox. Aged T cells are hyporesponsive to costimulation mediated by CD28. J Immunol 152 (1994) (3740 - 3747) CTLs that lack CD28 expression have little or no cytolytic activity. 21 x RB Effros. Genetic alterations in the ageing immune system: impact on infection and cancer. Mech Ageing Dev 124 (2003) (71 - 77) Crossref. Lack of CD28 expression on T cells is also associated with a decline in antibody responses to influenza vaccination. 22, x JJ Goronzy, JW Fulbright, CS Crowson, et al.. Value of immunological markers in predicting responsiveness to influenza vaccination in elderly individuals. J Virol 75 (2001) (12182 - 12187) Crossref. 23 x M Saurwein-Teissl, TL Lung, F Marx, et al.. Lack of antibody production following immunization in old age: association with CD8(+)CD28(-) T cell clonal expansions and an imbalance in the production of Th1 and Th2 cytokines. J Immunol 168 (2002) (5893 - 5899) Although the frequency of influenza virus-specific CTLs does not appreciably change with age, 24 x AC Boon, E Fringuelli, YM Graus, et al.. Influenza A virus specific T cell immunity in humans during aging. Virology 299 (2002) (100 - 108) Crossref. the decline in CTL activity is associated with decreases in influenza-specific CTL responses to influenza challenge 25 x JE McElhaney, D Xie, WD Hager, et al.. T cell responses are better correlates of vaccine protection in the elderly. J Immunol (2006) in press. and the production of cytolytic mediators including GrzB. 26 x JE McElhaney. The unmet need in the elderly: designing new influenza vaccines for older adults. Vaccine 23 (Suppl 1) (2005) (S10 - S25) Crossref. In addition to higher influenza attack rates in the population of 65 years and older, these changes in CTL function correspond to the related increased risk of serious complications that require hospitalization, prolong recovery from illness and may lead to death in older people (see also Chapter 5).

References

Label Authors Title Source Year
17

References in context

  • Recent studies suggest that although early immune responses to influenza may be similar in young and older adults, the ability to maintain or expand memory helper T cells that can respond to influenza challenge declines with ageing.17 Although mucosal and systemic antibodies are the first line of defence of the adaptive immune response, just increased levels of mucosal antibodies to influenza do not necessarily translate into clinically meaningful differences in protection against influenza.
    Go to context

I Kang, MS Hong, H Nolasco, et al.. Age-associated change in the frequency of memory CD4+ T cells impairs long term CD4+ T cell responses to influenza vaccine. J Immunol 173 (2004) (673 - 681) 2004
18

References in context

  • The age-related loss of CD28 expression on CTLs is associated with replicative senescence, growth arrest, increased production of several pro-inflammatory cytokines, resistance to apoptosis,18 and the loss of CD28-mediated costimulation required for optimal stimulation of CTLs.19,20 CTLs that lack CD28 expression have little or no cytolytic activity.21 Lack of CD28 expression on T cells is also associated with a decline in antibody responses to influenza vaccination.22,23 Although the frequency of influenza virus-specific CTLs does not appreciably change with age,24 the decline in CTL activity is associated with decreases in influenza-specific CTL responses to influenza challenge25 and the production of cytolytic mediators including GrzB.26 In addition to higher influenza attack rates in the population of 65 years and older, these changes in CTL function correspond to the related increased risk of serious complications that require hospitalization, prolong recovery from illness and may lead to death in older people (see also Chapter 5).
    Go to context

RB Effros, M Dagarag, HF Valenzuela. In vitro senescence of immune cells. Crossref. Exp Gerontol 38 (2003) (1243 - 1249) 2003
19

References in context

  • The age-related loss of CD28 expression on CTLs is associated with replicative senescence, growth arrest, increased production of several pro-inflammatory cytokines, resistance to apoptosis,18 and the loss of CD28-mediated costimulation required for optimal stimulation of CTLs.19,20 CTLs that lack CD28 expression have little or no cytolytic activity.21 Lack of CD28 expression on T cells is also associated with a decline in antibody responses to influenza vaccination.22,23 Although the frequency of influenza virus-specific CTLs does not appreciably change with age,24 the decline in CTL activity is associated with decreases in influenza-specific CTL responses to influenza challenge25 and the production of cytolytic mediators including GrzB.26 In addition to higher influenza attack rates in the population of 65 years and older, these changes in CTL function correspond to the related increased risk of serious complications that require hospitalization, prolong recovery from illness and may lead to death in older people (see also Chapter 5).
    Go to context

RB Effros, N Boucher, V Porter, et al.. Decline in CD28+ T cells in centenarians and in long-term T cell cultures: a possible cause for both in vivo and in vitro immunosenescence. Crossref. Exp Gerontol 29 (1994) (601 - 609) 1994
20

References in context

  • The age-related loss of CD28 expression on CTLs is associated with replicative senescence, growth arrest, increased production of several pro-inflammatory cytokines, resistance to apoptosis,18 and the loss of CD28-mediated costimulation required for optimal stimulation of CTLs.19,20 CTLs that lack CD28 expression have little or no cytolytic activity.21 Lack of CD28 expression on T cells is also associated with a decline in antibody responses to influenza vaccination.22,23 Although the frequency of influenza virus-specific CTLs does not appreciably change with age,24 the decline in CTL activity is associated with decreases in influenza-specific CTL responses to influenza challenge25 and the production of cytolytic mediators including GrzB.26 In addition to higher influenza attack rates in the population of 65 years and older, these changes in CTL function correspond to the related increased risk of serious complications that require hospitalization, prolong recovery from illness and may lead to death in older people (see also Chapter 5).
    Go to context

CR Engwerda, BS Handwerger, BS Fox. Aged T cells are hyporesponsive to costimulation mediated by CD28. J Immunol 152 (1994) (3740 - 3747) 1994
21

References in context

  • The age-related loss of CD28 expression on CTLs is associated with replicative senescence, growth arrest, increased production of several pro-inflammatory cytokines, resistance to apoptosis,18 and the loss of CD28-mediated costimulation required for optimal stimulation of CTLs.19,20 CTLs that lack CD28 expression have little or no cytolytic activity.21 Lack of CD28 expression on T cells is also associated with a decline in antibody responses to influenza vaccination.22,23 Although the frequency of influenza virus-specific CTLs does not appreciably change with age,24 the decline in CTL activity is associated with decreases in influenza-specific CTL responses to influenza challenge25 and the production of cytolytic mediators including GrzB.26 In addition to higher influenza attack rates in the population of 65 years and older, these changes in CTL function correspond to the related increased risk of serious complications that require hospitalization, prolong recovery from illness and may lead to death in older people (see also Chapter 5).
    Go to context

RB Effros. Genetic alterations in the ageing immune system: impact on infection and cancer. Crossref. Mech Ageing Dev 124 (2003) (71 - 77) 2003
22

References in context

  • The age-related loss of CD28 expression on CTLs is associated with replicative senescence, growth arrest, increased production of several pro-inflammatory cytokines, resistance to apoptosis,18 and the loss of CD28-mediated costimulation required for optimal stimulation of CTLs.19,20 CTLs that lack CD28 expression have little or no cytolytic activity.21 Lack of CD28 expression on T cells is also associated with a decline in antibody responses to influenza vaccination.22,23 Although the frequency of influenza virus-specific CTLs does not appreciably change with age,24 the decline in CTL activity is associated with decreases in influenza-specific CTL responses to influenza challenge25 and the production of cytolytic mediators including GrzB.26 In addition to higher influenza attack rates in the population of 65 years and older, these changes in CTL function correspond to the related increased risk of serious complications that require hospitalization, prolong recovery from illness and may lead to death in older people (see also Chapter 5).
    Go to context

JJ Goronzy, JW Fulbright, CS Crowson, et al.. Value of immunological markers in predicting responsiveness to influenza vaccination in elderly individuals. Crossref. J Virol 75 (2001) (12182 - 12187) 2001
23

References in context

  • The age-related loss of CD28 expression on CTLs is associated with replicative senescence, growth arrest, increased production of several pro-inflammatory cytokines, resistance to apoptosis,18 and the loss of CD28-mediated costimulation required for optimal stimulation of CTLs.19,20 CTLs that lack CD28 expression have little or no cytolytic activity.21 Lack of CD28 expression on T cells is also associated with a decline in antibody responses to influenza vaccination.22,23 Although the frequency of influenza virus-specific CTLs does not appreciably change with age,24 the decline in CTL activity is associated with decreases in influenza-specific CTL responses to influenza challenge25 and the production of cytolytic mediators including GrzB.26 In addition to higher influenza attack rates in the population of 65 years and older, these changes in CTL function correspond to the related increased risk of serious complications that require hospitalization, prolong recovery from illness and may lead to death in older people (see also Chapter 5).
    Go to context

M Saurwein-Teissl, TL Lung, F Marx, et al.. Lack of antibody production following immunization in old age: association with CD8(+)CD28(-) T cell clonal expansions and an imbalance in the production of Th1 and Th2 cytokines. J Immunol 168 (2002) (5893 - 5899) 2002
24

References in context

  • The age-related loss of CD28 expression on CTLs is associated with replicative senescence, growth arrest, increased production of several pro-inflammatory cytokines, resistance to apoptosis,18 and the loss of CD28-mediated costimulation required for optimal stimulation of CTLs.19,20 CTLs that lack CD28 expression have little or no cytolytic activity.21 Lack of CD28 expression on T cells is also associated with a decline in antibody responses to influenza vaccination.22,23 Although the frequency of influenza virus-specific CTLs does not appreciably change with age,24 the decline in CTL activity is associated with decreases in influenza-specific CTL responses to influenza challenge25 and the production of cytolytic mediators including GrzB.26 In addition to higher influenza attack rates in the population of 65 years and older, these changes in CTL function correspond to the related increased risk of serious complications that require hospitalization, prolong recovery from illness and may lead to death in older people (see also Chapter 5).
    Go to context

AC Boon, E Fringuelli, YM Graus, et al.. Influenza A virus specific T cell immunity in humans during aging. Crossref. Virology 299 (2002) (100 - 108) 2002
25

References in context

  • The age-related loss of CD28 expression on CTLs is associated with replicative senescence, growth arrest, increased production of several pro-inflammatory cytokines, resistance to apoptosis,18 and the loss of CD28-mediated costimulation required for optimal stimulation of CTLs.19,20 CTLs that lack CD28 expression have little or no cytolytic activity.21 Lack of CD28 expression on T cells is also associated with a decline in antibody responses to influenza vaccination.22,23 Although the frequency of influenza virus-specific CTLs does not appreciably change with age,24 the decline in CTL activity is associated with decreases in influenza-specific CTL responses to influenza challenge25 and the production of cytolytic mediators including GrzB.26 In addition to higher influenza attack rates in the population of 65 years and older, these changes in CTL function correspond to the related increased risk of serious complications that require hospitalization, prolong recovery from illness and may lead to death in older people (see also Chapter 5).
    Go to context

JE McElhaney, D Xie, WD Hager, et al.. T cell responses are better correlates of vaccine protection in the elderly. J Immunol (2006) in press. 2006
26

References in context

  • The age-related loss of CD28 expression on CTLs is associated with replicative senescence, growth arrest, increased production of several pro-inflammatory cytokines, resistance to apoptosis,18 and the loss of CD28-mediated costimulation required for optimal stimulation of CTLs.19,20 CTLs that lack CD28 expression have little or no cytolytic activity.21 Lack of CD28 expression on T cells is also associated with a decline in antibody responses to influenza vaccination.22,23 Although the frequency of influenza virus-specific CTLs does not appreciably change with age,24 the decline in CTL activity is associated with decreases in influenza-specific CTL responses to influenza challenge25 and the production of cytolytic mediators including GrzB.26 In addition to higher influenza attack rates in the population of 65 years and older, these changes in CTL function correspond to the related increased risk of serious complications that require hospitalization, prolong recovery from illness and may lead to death in older people (see also Chapter 5).
    Go to context

JE McElhaney. The unmet need in the elderly: designing new influenza vaccines for older adults. Crossref. Vaccine 23 (Suppl 1) (2005) (S10 - S25) 2005

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