Toll-like Receptors

For many years, it was not known how innate cells recognized foreign substances since they lacked the specific receptors that lymphocytes have. Then, receptors were discovered that can recognize patterns of molecules that pathogens have in common but that our bodies lack. An example is lipopolysaccharide (LPS) found in the outer membrane of gram negative bacteria. These groups of foreign molecules are called Pathogen Associated Molecular Patterns (PAMPs). Since the structures of the receptors that recognize these PAMPs were very similar to receptors called "Toll receptors," which are responsible for patterning during development in Drosophila, they were named "Toll-like Receptors" or TLRs.

There are ten functioning TLRs in humans. They are found on cells as diverse as monocytes, dendritic cells, intestinal cells, basophils, mast cells, B cells, and others. They can recognize products on an array of pathogens, from viruses to fungi. The PAMPs do not "fit" into the receptors, such as during T Cell receptor/antigen engagement, but rather work with other receptors on the cell surface when the pathogen is nearby. Once the receptor responds, it leads to a series of intracellular pathways that ultimately turn on a nuclear transcription factor. The nuclear transcription factor will then activate a gene, leading to the synthesis of a protein or other activity. Many cytokines are synthesized and secreted as a result of TLRs recognizing PAMPs.