How Pattern Recognition Receptors Provide Signal Two for Adaptive Immunity

The lecture traces how Charles Janeway proposed that pattern recognition receptors on innate immune cells detect conserved pathogen structures such as LPS and peptidoglycan, supplying the co-stimulatory second signal needed to activate adaptive immunity. Ruslan Medzhitov joined Janeway's lab in 1994 after reading his paper and cloned the first Toll-like receptor in 1996 using EST data and bioinformatic comparison of IL-1R and Toll intracellular domains; it later became known as TLR4, the LPS receptor complexed with MD2. The talk also covers how dendritic cells present peptide via MHC as signal one while pattern recognition induces CD80/CD86 co-stimulation and cytokines such as IL-12, and draws evolutionary parallels between Drosophila Toll and mammalian TLR pathways.