2.2 - Recognition of Microbes, Necrotic Cells, and Foreign Substances

Cells recognize dangerous material using pattern-recognition receptors.

recognition

inflammation has to be activated only when a dangerous signal is detected

• several cell types express receptors designated to recognize infectious pathogens and substances released from dead cells

  • phagocytes, dendritic cells, Langerhans cells, epithelial cells, other innate immune cells

• pattern recognition receptors → recognize molecular patterns associated with pathogens and injured cells

  • Toll-like receptors

  • inflammasome

Toll-like receptors (TLRs)

recognize molecular components of microbes and damaged cells that trigger production of inflammatory proteins

• recognize products of:

  • bacteria → endotoxin, bacterial DNA

  • viruses → double-stranded RNA

  • other pathogens

• located on:

  • plasma membranes → detect extracellular bacteria

  • endosomes → detect ingested bacteria

• recognition of pathogens activates transcription of inflammatory mediators, antiviral cytokines (interferons), and proteins that promote lymphocyte activation

  • recognition becomes inflammation through gene expression

inflammasome

intracellular multi-protein complex that detects danger signals and promotes production of active IL-1

• recognizes products of dead cells, uric acids, extracellular ATP, and some microbial products

  • extracellular ATP suggests cell membrane damage or cell death

• mechanism —

  1. danger signal activates inflammasome

  2. recognition triggers caspase-1

  3. cytokine IL-1β precursor cleaved to IL-1

  4. IL-1 involved in recruitment of WBCs in acute inflammation

inflamasome clinical connection

inflammasome also activated by uric acid crystals, cholesteral crystals, and fatty acids

• implicated in gout, atherosclerosis, and obesity-associated type 2 diabetes

• possibilities for therapy by blocking IL-1 to reduce inflammatory disease