Activation of the Innate Immune Response in Critical Illness

Abstract

Recognition molecules, inflammatory cells, and the cytokines they produce are the principle means for host tissues to recognize invading microbes, and to initiate intercellular communication between the innate and acquired immune systems. However, activation of host innate immunity may also occur in the absence of microbial recognition, through expression of internal “danger signals” produced by tissue ischemia and necrosis, or through the release of free radicals. When activation of the innate immune system is severe enough, the host response itself can propel the patient into a systemic inflammatory response syndrome (SIRS), or even multi-system organ failure (MSOF) and shock. Although the majority of patients survive the initial SIRS insult, these patients remain at increased risk of developing secondary or opportunistic infections due to the frequent onset of a compensatory anti-inflammatory response syndrome (CARS). The initial activation of the innate immune response often leads to macrophage deactivation, T-cell anergy, and the rapid apoptotic loss of lymphoid tissues, which all contribute to the development of this CARS syndrome and its associated morbidity and mortality. Initial efforts to treat the septic and critically ill patient with anti-cytokine therapies directed at the SIRS response have been disappointing, and therapeutic efforts to modify the immune response during sepsis syndromes will require a more thorough understanding of the innate and acquired immune responses.KeywordsNatural Killer CellSeptic ShockInnate Immune ResponseSystemic Inflammatory Response SyndromeInnate Immune SystemThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.