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Location, location, location.
"Most intuitive ligands for these receptors, such as LPS, only exist in bacterial outer membranes and are recognized, in this case, by TLR4 on the APC surface. Other ligands, such as dsRNA produced by viral replication, are sensed by a magnitude of intracellular and endosomal receptors (3, 4). Less intuitive are structures such as ssRNA or dsDNA, which are abundant in virtually all cell types, and hence do not appear to be ideal pathogen-associated molecular patterns because they are not exclusively pathogen associated. However, in this case, the immune system harnesses another fundamental aspect of cellular biology, namely subcellular location."
