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The Immune System in Critical Illness and Injury

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Pediatric Critical Care Medicine

Abstract

During the onset of critical illness or injury, initial attention is focused on supporting vital parameters for patient survival including oxygenation and tissue perfusion. Successful navigation past the primary insult often results in the patient with massive systemic inflammation and multi-organ dysfunction, thus at high risk for progression to organ failure, or secondary infection. It has become increasingly evident that the activation (or deactivation) state of the immune system is highly relevant to the prognosis of every critically ill or injured patient, not just those patients initially presenting with bacterial sepsis. Both the innate immune system, first described by Metchnikov in 1884 with his observations of phagocytosis, and the adaptive immune system are interconnected to sense and respond to invasion of the host by any pathogen. The outcome of these integrated the cellular and humoral responses can range from immediate termination of the microbe at site of invasion, with minimal systemic insult, to profound uncontrolled inflammation and organ damage, to systemic immunoparalysis and death from nosocomial sepsis. A broad overview of host defense is provided below with some discussion of how dysregulation of immune function impacts outcome in the critically ill patient.

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References

  1. Janeway Jr CA. Approaching the asymptote? Evolution and revolution in immunology. Cold Spring Harb Symp Quant Biol. 1989;54(Pt 1):1–13.

    Article  CAS  PubMed  Google Scholar 

  2. Blasius AL, Beutler B. Intracellular toll-like receptors. Immunity. 2010;32(3):305–15.

    Article  CAS  PubMed  Google Scholar 

  3. Kawai T, Akira S. Toll-like receptors and their crosstalk with other innate receptors in infection and immunity. Immunity. 2011;34(5):637–50.

    Article  CAS  PubMed  Google Scholar 

  4. Takeuchi O, Hoshino K, Akira S. Cutting edge: TLR2-deficient and MyD88-deficient mice are highly susceptible to Staphylococcus aureus infection. J Immunol. 2000;165(10):5392–6.

    Article  CAS  PubMed  Google Scholar 

  5. Weiss DS, Raupach B, Takeda K, Akira S, Zychlinsky A. Toll-like receptors are temporally involved in host defense. J Immunol. 2004;172(7):4463–9.

    Article  CAS  PubMed  Google Scholar 

  6. Bellocchio S, Montagnoli C, Bozza S, et al. The contribution of the Toll-like/IL-1 receptor superfamily to innate and adaptive immunity to fungal pathogens in vivo. J Immunol. 2004;172(5):3059–69.

    Article  CAS  PubMed  Google Scholar 

  7. Picard C, Puel A, Bonnet M, et al. Pyogenic bacterial infections in humans with IRAK-4 deficiency. Science. 2003;299(5615):2076–9.

    Article  CAS  PubMed  Google Scholar 

  8. von Bernuth H, Picard C, Jin Z, et al. Pyogenic bacterial infections in humans with MyD88 deficiency. Science. 2008;321(5889):691–6.

    Article  Google Scholar 

  9. Yang K, Puel A, Zhang S, et al. Human TLR-7-, -8-, and -9-mediated induction of IFN-alpha/beta and -lambda Is IRAK-4 dependent and redundant for protective immunity to viruses. Immunity. 2005;23(5):465–78.

    Article  CAS  PubMed  Google Scholar 

  10. Martinon F, Mayor A, Tschopp J. The inflammasomes: guardians of the body. Annu Rev Immunol. 2009;27:229–65.

    Article  CAS  PubMed  Google Scholar 

  11. Benko S, Philpott DJ, Girardin SE. The microbial and danger signals that activate Nod-like receptors. Cytokine. 2008;43(3):368–73.

    Article  CAS  PubMed  Google Scholar 

  12. Williams A, Flavell RA, Eisenbarth SC. The role of NOD-like receptors in shaping adaptive immunity. Curr Opin Immunol. 2010;22(1):34–40.

    Article  CAS  PubMed  Google Scholar 

  13. Masters SL, Simon A, Aksentijevich I, Kastner DL. Horror autoinflammaticus: the molecular pathophysiology of autoinflammatory disease . Annu Rev Immunol. 2009;27:621–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Pichlmair A, Reis e Sousa C. Innate recognition of viruses. Immunity. 2007;27(3):370–83.

    Article  CAS  PubMed  Google Scholar 

  15. Bottazzi B, Doni A, Garlanda C, Mantovani A. An integrated view of humoral innate immunity: pentraxins as a paradigm. Annu Rev Immunol. 2010;28:157–83.

    Article  CAS  PubMed  Google Scholar 

  16. Haagsman HP, Hogenkamp A, van Eijk M, Veldhuizen EJ. Surfactant collectins and innate immunity. Neonatology. 2008;93(4):288–94.

    Article  PubMed  Google Scholar 

  17. Garred P, Honore C, Ma YJ, Munthe-Fog L, Hummelshoj T. MBL2, FCN1, FCN2 and FCN3-The genes behind the initiation of the lectin pathway of complement. Mol Immunol. 2009;46(14):2737–44.

    Article  CAS  PubMed  Google Scholar 

  18. Deban L, Jaillon S, Garlanda C, Bottazzi B, Mantovani A. Pentraxins in innate immunity: lessons from PTX3. Cell Tissue Res. 2011;343(1):237–49.

    Article  CAS  PubMed  Google Scholar 

  19. Lakshman R, Finn A. Neutrophil disorders and their management. J Clin Pathol. 2001;54(1):7–19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Dinauer MC. Disorders of neutrophil function: an overview. Methods Mol Biol. 2007;412:489–504.

    Article  CAS  PubMed  Google Scholar 

  21. Kobayashi SD, DeLeo FR. Role of neutrophils in innate immunity: a systems biology-level approach. Wiley Interdiscip Rev Syst Biol Med. 2009;1(3):309–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Leon B, Ardavin C. Monocyte-derived dendritic cells in innate and adaptive immunity. Immunol Cell Biol. 2008;86(4):320–4.

    Article  CAS  PubMed  Google Scholar 

  23. Geissmann F, Manz MG, Jung S, Sieweke MH, Merad M, Ley K. Development of monocytes, macrophages, and dendritic cells. Science. 2010;327(5966):656–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Vivier E, Raulet DH, Moretta A, et al. Innate or adaptive immunity? The example of natural killer cells. Science. 2011;331(6013):44–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Rus H, Cudrici C, Niculescu F. The role of the complement system in innate immunity. Immunol Res. 2005;33(2):103–12.

    Article  CAS  PubMed  Google Scholar 

  26. Degn SE, Jensenius JC, Thiel S. Disease-causing mutations in genes of the complement system. Am J Hum Genet. 2011;88(6):689–705.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Guani-Guerra E, Santos-Mendoza T, Lugo-Reyes SO, Teran LM. Antimicrobial peptides: general overview and clinical implications in human health and disease. Clin Immunol. 2010;135(1):1–11.

    Article  CAS  PubMed  Google Scholar 

  28. Takahama Y. Journey through the thymus: stromal guides for T-cell development and selection. Nat Rev Immunol. 2006;6(2):127–35.

    Article  CAS  PubMed  Google Scholar 

  29. Cossu F. Genetics of SCID. Ital J Pediatr. 2010;36:76.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Mosmann TR, Cherwinski H, Bond MW, Giedlin MA, Coffman RL. Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol. 1986;136(7):2348–57.

    CAS  PubMed  Google Scholar 

  31. Bonilla FA, Oettgen HC. Adaptive immunity. J Allergy Clin Immunol. 2010;125(2 Suppl 2):S33–40.

    Article  PubMed  Google Scholar 

  32. Meraviglia S, El Daker S, Dieli F, Martini F, Martino A. gammadelta T cells cross-link innate and adaptive immunity in Mycobacterium tuberculosis infection. Clin Dev Immunol. 2011;2011:587315.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Conley ME, Dobbs AK, Farmer DM, et al. Primary B cell immunodeficiencies: comparisons and contrasts. Annu Rev Immunol. 2009;27:199–227.

    Article  CAS  PubMed  Google Scholar 

  34. Guarda G, Dostert C, Staehli F, et al. T cells dampen innate immune responses through inhibition of NLRP1 and NLRP3 inflammasomes. Nature. 2009;460(7252):269–73.

    Article  CAS  PubMed  Google Scholar 

  35. Shanker A. Adaptive control of innate immunity. Immunol Lett. 2010;131(2):107–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Ward NS, Casserly B, Ayala A. The compensatory anti-inflammatory response syndrome (CARS) in critically ill patients. Clin Chest Med. 2008;29(4):617–25. viii.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Hotchkiss RS, Coopersmith CM, McDunn JE, Ferguson TA. The sepsis seesaw: tilting toward immunosuppression. Nat Med. 2009;15(5):496–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Polk Jr HC, George CD, Wellhausen SR, et al. A systematic study of host defense processes in badly injured patients. Ann Surg. 1986;204(3):282–99.

    PubMed  PubMed Central  Google Scholar 

  39. Livingston DH, Appel SH, Wellhausen SR, Sonnenfeld G, Polk Jr HC. Depressed interferon gamma production and monocyte HLA-DR expression after severe injury. Arch Surg. 1988;123(11):1309–12.

    Article  CAS  PubMed  Google Scholar 

  40. Cheadle WG, Wilson M, Hershman MJ, Bergamini D, Richardson JD, Polk Jr HC. Comparison of trauma assessment scores and their use in prediction of infection and death. Ann Surg. 1989;209(5):541–5. discussion 545 –546.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Volk HD, Reinke P, Krausch D, et al. Monocyte deactivation–rationale for a new therapeutic strategy in sepsis. Intensive Care Med. 1996;22 Suppl 4:S474–81.

    Article  PubMed  Google Scholar 

  42. Baehr RV, Volk HD, Reinke P, Falck P, Wolff H. An immune monitoring program for controlling immunosuppressive therapy. Transplant Proc. 1989;21(1 Pt 1):1189–91.

    CAS  PubMed  Google Scholar 

  43. Greenman RL, Schein RM, Martin MA, et al. A controlled clinical trial of E5 murine monoclonal IgM antibody to endotoxin in the treatment of gram-negative sepsis. The XOMA Sepsis Study Group. JAMA. 1991;266(8):1097–102.

    Article  CAS  PubMed  Google Scholar 

  44. Fisher Jr CJ, Dhainaut JF, Opal SM, et al. Recombinant human interleukin 1 receptor antagonist in the treatment of patients with sepsis syndrome. Results from a randomized, double-blind, placebo-controlled trial. Phase III rhIL-1ra Sepsis Syndrome Study Group. JAMA. 1994;271(23):1836–43. Jun 15.

    Article  PubMed  Google Scholar 

  45. Fisher Jr CJ, Agosti JM, Opal SM, et al. Treatment of septic shock with the tumor necrosis factor receptor:Fc fusion protein. The Soluble TNF Receptor Sepsis Study Group. N Engl J Med. 1996;334(26):1697–702.

    Article  CAS  PubMed  Google Scholar 

  46. Cohen J, Carlet J. INTERSEPT: an international, multicenter, placebo-controlled trial of monoclonal antibody to human tumor necrosis factor-alpha in patients with sepsis. International Sepsis Trial Study Group. Crit Care Med. 1996;24(9):1431–40.

    Article  CAS  PubMed  Google Scholar 

  47. Bone RC. Why sepsis trials fail. JAMA. 1996;276(7):565–6.

    Article  CAS  PubMed  Google Scholar 

  48. Bone RC. Sir Isaac Newton, sepsis, SIRS, and CARS. Crit Care Med. 1996;24(7):1125–8.

    Article  CAS  PubMed  Google Scholar 

  49. Frazier WJ, Hall MW. Immunoparalysis and adverse outcomes from critical illness. Pediatr Clin North Am. 2008;55(3):647–68. xi.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Monneret G, Lepape A, Voirin N, et al. Persisting low monocyte human leukocyte antigen-DR expression predicts mortality in septic shock. Intensive Care Med. 2006;32(8):1175–83.

    Article  PubMed  Google Scholar 

  51. Ho YP, Sheen IS, Chiu CT, Wu CS, Lin CY. A strong association between down-regulation of HLA-DR expression and the late mortality in patients with severe acute pancreatitis. Am J Gastroenterol. 2006;101(5):1117–24.

    Article  CAS  PubMed  Google Scholar 

  52. Osuchowski MF, Welch K, Siddiqui J, Remick DG. Circulating cytokine/inhibitor profiles reshape the understanding of the SIRS/CARS continuum in sepsis and predict mortality. J Immunol. 2006;177(3):1967–74.

    Article  CAS  PubMed  Google Scholar 

  53. Muenzer JT, Davis CG, Chang K, et al. Characterization and modulation of the immunosuppressive phase of sepsis. Infect Immun. 2010;78(4):1582–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Inoue S, Unsinger J, Davis CG, et al. IL-15 prevents apoptosis, reverses innate and adaptive immune dysfunction, and improves survival in sepsis. J Immunol. 2010;184(3):1401–9.

    Article  CAS  PubMed  Google Scholar 

  55. Nierhaus A, Montag B, Timmler N, et al. Reversal of immunoparalysis by recombinant human granulocyte-macrophage colony-stimulating factor in patients with severe sepsis. Intensive Care Med. 2003;29(4):646–51.

    Article  PubMed  Google Scholar 

  56. Meisel C, Schefold JC, Pschowski R, et al. Granulocyte-macrophage colony-stimulating factor to reverse sepsis-associated immunosuppression: a double-blind, randomized, placebo-controlled multicenter trial. Am J Respir Crit Care Med. 2009;180(7):640–8.

    Article  CAS  PubMed  Google Scholar 

  57. Hall MW, Knatz NL, Vetterly C, et al. Immunoparalysis and nosocomial infection in children with multiple organ dysfunction syndrome. Intensive Care Med. 2011;37(3):525–32.

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Jessica G. Moreland MD .

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Moreland, J.G. (2014). The Immune System in Critical Illness and Injury. In: Wheeler, D., Wong, H., Shanley, T. (eds) Pediatric Critical Care Medicine. Springer, London. https://doi.org/10.1007/978-1-4471-6416-6_28

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  • DOI: https://doi.org/10.1007/978-1-4471-6416-6_28

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