Toll-like receptors (TLRs) are single, membrane spanning, protein receptors which play a valuable role in the innate immunity of a person. It initiates the recognition of certain molecular patters derived from microbial cells invading the human body and signals the beginning of a cascading pathway resulting in the elimination of the invading pathogen in most instances. Due to the cell mediated initial immunity not lasting to provide long-term immunity from the same pathogen, it is considered an ‘innate immune response’.
Discovery of the toll-like receptors:
The term ‘toll’ which refers to ‘amazing’ or ‘great’ in German was given to the toll-like receptors following its resemblance to the toll receptors found in Drosophila, as far back as 1985. The elated team of discoverers expressed their amazement by shouting ‘toll…toll’ which made the receptors be named in the same way.
Structure of the TLR:
These receptors are known as type 1 transmembrane protein which means that they will have an extra cellular component, a transmembrane portion and an intra-cellular or cytoplasmic component. According to researchers, the extracellular portion of the receptor resembles the shape of a large horseshoe while the cytoplasmic component resembles a ‘tail’ extending from the membrane of the cell.
The toll-like receptors are located in large numbers in places such as the spleen, peripheral blood leukocytes and places such as the intestine and the lungs. The reason for their larger presence in such places is the increased susceptibility of these locations to be exposed to invading organisms from the outside environment or through circulation.
The function of TLRs:
The uniqueness of the TLRs is their ability to recognize molecular patterns specific to invading microorganisms which are known as pathogen-associated microbial patterns (PAMPs). Stimulation of the TLRs with PAMPs will initiate a signaling cascade through proteins such as MyD88, TRIF and IRAK. As a result, several factors known as transcription factors which include AP-1, NF-Kb AND IRFs will initiate the secretion of inflammatory cytokines that would direct its effects on the invading organism. Furthermore, some of the induced cytokines have the ability to direct the adaptive immune response which is the long-term immunity one gains following being exposed to certain microorganisms or molecules.
In case of bacterial pathogens, the final outcome of the activation of toll-like receptors would be the phagocytosis (the process in which the pathogenic organism is being engulfed by a cell membrane) and digestion of the same. In case of a viral pathogen, the infected cell containing the TLRs will terminate its protein synthesis and initiate a process of self destruction. Furthermore, release of antiviral factors may also take place as a result of the signaling process.