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The Immune Response to Influenza Infection

The innate immune response

Key features of the innate response

The “innate immune response” is stimulated when cells are infected with viral, bacterial or fungal pathogens. The influenza virus induces chemokine and cytokine production by infected epithelial cells and monocytes/macrophages. These chemokines attract immune cells to the site of infection, including macrophages, neutrophils and natural killer (NK) cells, as summarized in Table 5 . These in turn produce additional cytokines, chemokines and other antiviral proteins. 8 x I Julkunen, K Melen, M Nyqvist, J Pirhonen, T Sareneva, S Matikainen. Inflammatory responses in influenza A virus infection. Vaccine 19 (Suppl 1) (2000) (S32 - S37) Crossref. This process activates a number of immune cells, including those of the adaptive immune response.

Table 5 Components of the innate immune response. source: Reproduced from Griffin J et al. Crash Course: Immunology and Haematology, 2003 with permission from Elsevier.

Components of the innate immune response
Innate system
Cellular components Monocytes/macrophages
Neutrophils
Eosinophils
Basophils
Mast cells
Natural killer cells
Secreted components Complement
Cytokines
Lysozyme
Acute phase proteins
Interferons

References in context

  • These chemokines attract immune cells to the site of infection, including macrophages, neutrophils and natural killer (NK) cells, as summarized in Table 5.
    Go to context

Type I interferons (IFN-α/β) are among the most important cytokines produced by the innate immune response and have several important antiviral functions. Firstly, they bind to neighbouring cells and induce an antiviral state by promoting the production of several intracellular antiviral proteins that inhibit protein synthesis (including, of course, viral proteins). Secondly, they recruit monocytes/macrophages, T cells and NK cells. Thirdly. they enhance maturation of antigen-presenting cells (APCs) and increase the expression of major histocompatibility complex (MHC) class I and II molecules on APCs, resulting in enhanced antigen presentation, which facilitates adaptive immune mechanisms.

In addition to cytokines, NK cells play an important role in the innate immune response against viral infections. NK cells are large granular lymphocytes that detect virus-infected cells in a non-specific manner. Many viruses induce a down-regulation of MHC class I molecules on the surface of infected cells, so as to escape destruction by CTLs. NK cells, however, sense the loss of MHC class I molecules on the surface of these cells, and destroy them by apoptosis. 9 x JA Trapani, MJ Smyth. Killing by cytotoxic T cells and natural killer cells: multiple granule serine proteases as initiators of DNA fragmentation. Immunol Cell Biol 71 (Pt 3) (1993) (201 - 208) Crossref. 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.

Implications for the immunopathogenesis of influenza

High levels of cytokines are produced in the inflammatory, antiviral response to the large quantities of virus that may be produced in the absence of an adaptive immune response. Desquamation of the respiratory epithelium combined with inflammatory processes leads to transudation of large amounts of fluid into the lungs. Progressive hypoxia and acute respiratory distress syndrome may cause death within the first 1–2 days of the onset of illness. This process is more likely to occur with pandemic influenza where the individual has not been exposed to the new virus subtype before and must rely on the innate immune response to decrease viral replication. The adaptive immune system must mount a primary response, which is delayed because of a lack of prior exposure to the new subtype of influenza virus.

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, x TM Tumpey, CF Basler, PV Aguilar, et al.. Characterization of the reconstructed 1918 Spanish influenza pandemic virus. Science 310 (2005) (77 - 80) Crossref. 11 x 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. J Virol 79 (2005) (14933 - 14944) Crossref. 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. The limited efficacy of the innate immune response against the 1918 virus appears to be related to adaptation of the NS1 gene to efficiently suppress the IFN-α/β system, thus allowing an almost unrestricted replication of the virus.

 
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Table 5 Components of the innate immune response. source: Reproduced from Griffin J et al. Crash Course: Immunology and Haematology, 2003 with permission from Elsevier.

Components of the innate immune response
Innate system
Cellular components Monocytes/macrophages
Neutrophils
Eosinophils
Basophils
Mast cells
Natural killer cells
Secreted components Complement
Cytokines
Lysozyme
Acute phase proteins
Interferons

References in context

  • These chemokines attract immune cells to the site of infection, including macrophages, neutrophils and natural killer (NK) cells, as summarized in Table 5.
    Go to context

References

Label Authors Title Source Year
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

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