Lecture Notes: Pattern Recognition Receptors in Innate Immunity

Introduction

• Focus on pattern recognition receptors (PRRs) in innate immunity.
• PRRs detect infection or tissue damage, initiating signaling cascades.

Key Concepts

• Pathogen-associated molecular patterns (PAMPs): Unique to pathogens, e.g., bacterial cell walls, single or double-stranded viral DNA.
• Damage-associated molecular patterns (DAMPs): Host molecules out of place, e.g., extracellular ATP indicating cell damage.
• Location of PRRs: Key to their function—can be extracellular, intracellular, or within endosomes.

Pattern Recognition Receptors (PRRs)

• Toll-like Receptors (TLRs):
  • Ancient sensors found in various organisms.
  • Structure: Single-pass transmembrane proteins with leucine-rich repeats.
  • Signaling: TIR domains for interacting with adaptor proteins (MyD88, TRIF, Mal, TRAM).
  • Signaling Pathways:
    • MyD88 Pathway: Involves IRAK kinases, TRAF6, NF-κB activation.
    • TRIF Pathway: Involves TRAF6, TRAF3; leads to NF-kB and IRF3 activation.

Specific TLRs and Their Ligands

• TLR-2: Binds bacterial lipoproteins/lipoteichoic acid.
• TLR-3: Recognizes double-stranded RNA.
• TLR-4: Senses LPS from Gram-negative bacteria, uses four adaptor proteins.
• TLR-5: Binds bacterial flagellin.
• TLR-7: Binds single-stranded RNA.
• TLR-9: Recognizes unmethylated CpG DNA.

Other Pattern Recognition Receptors

• NOD-like Receptors (NLRs):

  • Intracellular sensors for microbial products.
  • Recognize peptidoglycan, activate NF-κB.

• RIG-I-like Helicases:

  • Sense viral nucleic acids in the cytoplasm.
  • Activation produces type I interferons.

DAMP Sensing

• Specific DAMP Receptors:
  • P2X7: Senses extracellular ATP.
  • RAGE: Senses extracellular HMGB1 and S100 proteins.
• Overlapping Recognition:
  • Some PRRs recognize both PAMPs and DAMPs, e.g., TLR-4.

Conclusion

• PRRs play a crucial role in the innate immune response.
• They provide a rapid response mechanism by recognizing a broad range of pathogenic and damage-related signals.
• Upcoming topics will include the adaptive immune system and antigen-specific responses.