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Immunology of Auto-inflammatory Syndromes

  • Grant S. SchulertEmail author
Chapter

Abstract

The body’s first line of defense is the innate immune system, an ancestrally ancient response distinct from the adaptive immune system. At the heart of innate immunity are host germline-encoded pattern recognition receptors, which sense conserved structural features present on pathogens or signs of tissue damage, and trigger production of inflammatory responses. In contrast, autoinflammation represents a disordered and inappropriate innate immune response, with excessive production of inflammatory cytokines in the absence of high-titer autoantibodies and antigen-specific T cells. This chapter reviews the innate immune system, with a particular focus on how defects in these immune sensors and their associated signaling pathways are linked to autoinflammation. Central to this is a large family of intracellular pattern recognition receptors including the nucleotide-binding oligomerization domain (NOD) proteins and the NOD-like receptors (NLRs), which serve as key mediators in both innate immunity and autoinflammation largely through ability to form inflammasomes. Indeed, many autoinflammatory disorders converge at the level of inflammasome activation. Inflammasomes and other sensors trigger rapid production of inflammatory cytokines, and defective regulation and attenuation of cytokine responses can also underlie autoinflammation. In addition, the type I interferon response represents a distinct innate immune pathway able to elicit a potent antiviral response but when dysregulated is increasingly recognized as an important cause of autoinflammation. The objective of this overview of innate immune responses is to provide a framework for understanding autoinflammation and inform clinical diagnosis and rationally directed therapies.

Keywords

Innate immunity Inflammasome Nucleotide-oligomerization domain (NOD) protein NOD-like receptor Cytokine Cytokine storm syndrome Type I interferon 

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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Division of RheumatologyCincinnati Children’s Hospital Medical CenterCincinnatiUSA
  2. 2.Department of PediatricsUniversity of CincinnatiCincinnatiUSA

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