LECTURE #3 – TLR SIGNALING
After studying lecture #3, you should be familiar with the following concepts.
1. PAMP- PRR Interactions. Pathogen Associated Molecular Patterns (PAMP) are
microbial molecules that interact with host Pattern Recognition Receptors (PRR) to alert
a host to microbial presence/invasion. Once active, host PRR initiate intracellular
signaling cascades that drive rapid innate immune defenses. PAMP/PRR-based
defenses are ancient and evolutionarily conserved.
2. Toll-Like Receptors (TLR). TLR are classical PRR that illuminate many key features
of the signaling pathways that underpin innate immune responses. TLR have a modular
architecture with three distinct domains. The N-terminal Leucine Rich Repeats (LRR)
bind PAMPs. The transmembrane domain anchors TLR in the membrane and ensure
that TLR have appropriate access to PAMPs. The C-terminal intracellular Toll Internal
Repeat (TIR) engage intracellular adaptor molecules to initiate TLR signaling. There are
numerous versions of TLR (e.g. approx. ten in the human genome) with varying
specificities and distinct signaling outcomes. This ensures that the correc