Pattern Recognition Receptors (PRRs)
Most PRRs are found in our immune cells. However, other cells at the interface with the external environment, like epithelial cells, also express some PRRs. The PRR expressing cells expose their PRRs at all times regardless of their life cycle and also express many different types of PRRs with differing PAMP specificities. The different types of PRRs also locate to sites on the cell surface or within the cell where their specific PAMPs are most likely found. The importance of the location of our PRRs is the main focus of the following pages. However, all the above PRRs features help maximise detection of invading pathogens.
In the graphic below (click link to activate zoom) you can see four different types of PRRs. The Toll-like receptors (TLRs), C-type lectin receptors (CLRs), the RIG-like receptors (RLR) and NOD-like receptors (NLR). Notice how TLRs and CLRs are associated with a membrane.
TLRs and CLRs have a PAMP detecting part facing the extracellular environment and a signalling part in the cytosol. CLRs contain a lectin domain specialised in binding carbohydrates. CLRs, like Dectin-1, are thereby excellent in recognising microbial glycoproteins, like fungal β(1,3)-glucans. TLRs on the other hand are built to bind a huge variety of PAMP structures including carbohydrates, lipids and nucleic acids.
Why do you think there are TLRs with a PAMP detecting part inside the endosome? You can find the answer is this video clip. While watching this clip, also try to locate the RLRs and NLRs and think of why they are found where they are. This video should also help you answer the DNA question from the previous page, if you think of where mammalian cells store their DNA.
So how do PRRs actually help destroying pathogens? Well, in the video you saw how recognition of a PAMP by a PRR resulted in transcription of genes. The narrator mentioned that activation of NLRs and RLRs leads the production of type I interferons. Signalling from TLRs also result in gene transcription, this time leading to the production of pro-inflammatory cytokines like TNF-α and IL-1β. All these so called cytokines affect surrounding cells leading to the inflammatory response and the destruction of pathogens. Signalling from CLRs can in addition lead to instant removal of the pathogen by the cell itself via phagocytosis.
We have now seen how PRRs quickly can detect and start the elimination of pathogens. But PRRs not only bind PAMPs but some also bind self molecules. To stop unwanted immune responses to "self", the cells have had to carefully segregate these PRRs from their potential self triggers, as you saw with the DNA detecting PRRs that are kept away from the DNA stored in the nucleus. But these self reactive PRRs are not just a nuance but also crucially important controllers of immune responses that will be discussed in the next section on "Danger Signals".