Elsevier Health Sciences

Topics

« Back to Resource Center

The Immune Response to Influenza Infection

References

Label Authors Title Source Year
1

References in context

  • While the innate immune system recognizes virus-infected cells through mechanisms that are not antigen-specific, the cytokines produced during this early phase of the host's defence do facilitate activation of subsequent antigen-specific adaptive immune mechanisms.1 An important element of the transition from the innate to the adaptive immune response is the stimulation of Toll-like receptors (TLRs) in endosomes of antigen-presenting cells (primarily dendritic cells).2 TLRs recognize and bind to structural components such as single-stranded viral RNA, which are shared by different pathogens, and are important triggers of the “danger signal”.
    Go to context

JE Durbin, A Fernandez-Sesma, CK Lee, et al.. Type I IFN modulates innate and specific antiviral immunity. J Immunol 164 (2000) (4220 - 4228) 2000
2

References in context

  • While the innate immune system recognizes virus-infected cells through mechanisms that are not antigen-specific, the cytokines produced during this early phase of the host's defence do facilitate activation of subsequent antigen-specific adaptive immune mechanisms.1 An important element of the transition from the innate to the adaptive immune response is the stimulation of Toll-like receptors (TLRs) in endosomes of antigen-presenting cells (primarily dendritic cells).2 TLRs recognize and bind to structural components such as single-stranded viral RNA, which are shared by different pathogens, and are important triggers of the “danger signal”.
    Go to context

SS Diebold, T Kaisho, H Hemmi, et al.. Innate antiviral responses by means of TLR7-mediated recognition of single-stranded RNA. Crossref. Science 303 (2004) (1529 - 1531) 2004
3

References in context

  • A major aspect of the adaptive immune response involves virus binding to immunoglobulin receptors on B lymphocytes, which subsequently differentiate to plasma cells that produce virus-specific antibodies.3 Activation of the adaptive immune response occurs through peptides derived from viral proteins, which are presented on antigen-presenting cells to the T lymphocytes.
    Go to context

BO Lee, J Rangel-Moreno, JE Moyron-Quiroz, et al.. CD4 T cell-independent antibody response promotes resolution of primary influenza infection and helps to prevent reinfection. J Immunol 175 (2005) (5827 - 5838) 2005
4

References in context

  • Helper T cells, through the production of cytokines, contribute to B cell proliferation and differentiation to plasma cells, and to the activation and proliferation of virus-specific cytotoxic T lymphocytes (CTLs).4 Figure 16 details many of the interactions of the different cell populations involved.
    Go to context

  • The mechanisms by which CTLs induce lysis of virus-infected cells include perforin- or granule-mediated killing.4 Granule-mediated killing appears to be the critical effector function of CTLs against influenza-infected cells.
    Go to context

PC Doherty, DJ Topham, RA Tripp, et al.. Effector CD4+ and CD8+ T-cell mechanisms in the control of respiratory virus infections. Crossref. Immunol Rev 159 (1997) (105 - 117) 1997
5

References in context

  • T helper (Th1 and Th2) cytokines reciprocally down-regulate each other and only Th1 cytokines facilitate CTL activation.5 Activation of CTLs and the associated increase in granzyme B (Grz B) that leads to programmed cell death (apoptosis) of virus-infected cells is another critical component of the adaptive antiviral immune response.6,7 With ageing, the loss of CTL-mediated immunity has been directly linked to the increased risk of influenza illness in older people, while antibody responses appear to be relatively preserved in otherwise healthy older adults.
    Go to context

PC Doherty, W Allan, M Eichelberger, SR Carding. Roles of alpha beta and gamma delta T cell subsets in viral immunity. Crossref. Ann Rev Immunol 10 (1992) (123 - 151) 1992
6

References in context

  • T helper (Th1 and Th2) cytokines reciprocally down-regulate each other and only Th1 cytokines facilitate CTL activation.5 Activation of CTLs and the associated increase in granzyme B (Grz B) that leads to programmed cell death (apoptosis) of virus-infected cells is another critical component of the adaptive antiviral immune response.6,7 With ageing, the loss of CTL-mediated immunity has been directly linked to the increased risk of influenza illness in older people, while antibody responses appear to be relatively preserved in otherwise healthy older adults.
    Go to context

BJ Johnson, EO Costelloe, DR Fitzpatrick, et al.. Single-cell perforin and granzyme expression reveals the anatomical localization of effector CD8+ T cells in influenza virus-infected mice. Crossref. Proc Natl Acad Sci USA 100 (2003) (2657 - 2662) 2003
7

References in context

  • T helper (Th1 and Th2) cytokines reciprocally down-regulate each other and only Th1 cytokines facilitate CTL activation.5 Activation of CTLs and the associated increase in granzyme B (Grz B) that leads to programmed cell death (apoptosis) of virus-infected cells is another critical component of the adaptive antiviral immune response.6,7 With ageing, the loss of CTL-mediated immunity has been directly linked to the increased risk of influenza illness in older people, while antibody responses appear to be relatively preserved in otherwise healthy older adults.
    Go to context

CW Lawrence, RM Ream, TJ Braciale. Frequency, specificity, and sites of expansion of CD8+ T cells during primary pulmonary influenza virus infection. J Immunol 174 (2005) (5332 - 5340) 2005
8

References in context

  • These in turn produce additional cytokines, chemokines and other antiviral proteins.8 This process activates a number of immune cells, including those of the adaptive immune response.
    Go to context

I Julkunen, K Melen, M Nyqvist, J Pirhonen, T Sareneva, S Matikainen. Inflammatory responses in influenza A virus infection. Crossref. Vaccine 19 (Suppl 1) (2000) (S32 - S37) 2000
9

References in context

  • NK cells, however, sense the loss of MHC class I molecules on the surface of these cells, and destroy them by apoptosis.9 The innate immune response is activated within a few hours of infection and lasts for as long as 7 days during a primary influenza infection, when the adaptive immune response takes longer to be activated.
    Go to context

JA Trapani, MJ Smyth. Killing by cytotoxic T cells and natural killer cells: multiple granule serine proteases as initiators of DNA fragmentation. Crossref. Immunol Cell Biol 71 (Pt 3) (1993) (201 - 208) 1993
10

References in context

  • Recently it has been shown in mice that the lethality of the 1918 pandemic influenza virus is related to high levels of virus replication, severe lung inflammation and infiltration of the lungs with neutrophils and alveolar macrophages.10,11 These elements are the result of an ineffective innate immune response to control replication of this subtype of influenza in the absence of an adaptive immune response.
    Go to context

TM Tumpey, CF Basler, PV Aguilar, et al.. Characterization of the reconstructed 1918 Spanish influenza pandemic virus. Crossref. Science 310 (2005) (77 - 80) 2005
11

References in context

  • Recently it has been shown in mice that the lethality of the 1918 pandemic influenza virus is related to high levels of virus replication, severe lung inflammation and infiltration of the lungs with neutrophils and alveolar macrophages.10,11 These elements are the result of an ineffective innate immune response to control replication of this subtype of influenza in the absence of an adaptive immune response.
    Go to context

TM Tumpey, A Garcia-Sastre, JK Taubenberger, et al.. Pathogenicity of influenza viruses with genes from the 1918 pandemic virus: functional roles of alveolar macrophages and neutrophils in limiting virus replication and mortality in mice. Crossref. J Virol 79 (2005) (14933 - 14944) 2005
12

References in context

  • MHC molecules present peptide fragments derived from viral proteins either degraded or synthesized inside the cell, and the MHC–peptide complex is transported to the cell surface, where the complex can be recognized by the T cell receptor.12 Antigen-presenting cells (APCs) have different pathways of antigen processing for class I and class II MHC, and different requirements for loading peptides from live or killed virus onto the MHC class I molecules (see Figure 17).
    Go to context

TJ Braciale, LA Morrison, MT Sweetser, et al.. Antigen presentation pathways to class I and class II MHC-restricted T lymphocytes. Crossref. Immunol Rev 98 (1987) (95 - 114) 1987
13

References in context

  • Human studies showed that CTL activity is important for recovery from influenza infection even in the presence of protective antibodies to the infecting virus strain.13 CTLs combat influenza viral infections by recognizing and destroying virus-infected host cells that otherwise become the factories for viral replication.
    Go to context

AJ McMichael, FM Gotch, GR Noble, PA Beare. Cytotoxic T-cell immunity to influenza. Crossref. New Engl J Med 309 (1983) (13 - 17) 1983
14

References in context

  • In contrast to the antibody response to a specific strain of influenza virus, T cell responses tend to be cross-protective within the types and subtypes of influenza, as the viral peptides that stimulate the T cell response are relatively more conserved than antibody binding sites across the different strains of influenza.14 Internal peptide sequences of HA and NA are similar within the subtypes of influenza (e.g.
    Go to context

PG Thomas, R Keating, DJ Hulse-Post, PC Doherty. Cell-mediated protection in influenza infection. Crossref. Emerg Infect Dis 12 (2006) (48 - 54) 2006
15

References in context

  • Although T cell responses are much more cross-reactive compared to antibody responses, recent data suggest that antigenic drift also affects CTL responses against NP as soon as immunological pressure is applied.15 Although B cell memory is largely strain-specific, it lasts a lifetime.
    Go to context

GF Rimmelzwaan, AC Boon, JT Voeten, et al.. Sequence variation in the influenza A virus nucleoprotein associated with escape from cytotoxic T lymphocytes. Crossref. Virus Res 103 (2004) (97 - 100) 2004
16

References in context

  • In contrast to the antibody response to a specific strain of influenza virus, T cell responses tend to be cross-protective within the types and subtypes of influenza, as the viral peptides that stimulate the T cell response are relatively more conserved than antibody binding sites across the different strains of influenza.14 Internal peptide sequences of HA and NA are similar within the subtypes of influenza (e.g.
    Go to context

FA Ennis, Q Yi-Hua, GC Schild. Antibody and cytotoxic T lymphocyte responses of humans to live and inactivated influenza vaccines. Crossref. J Gen Virol 58 (1982) (273 - 281) 1982
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

« Back to Resource Center