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Toll-like Receptors
Written by Tim Sheppard MBBS BSc. Created 29/3/10; last updated 29/3/10

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What are Toll-like receptors?

The body has two main types of dealing with invaders. One is specially designed to respond in a very specific way to any enemies that it has seen before, by recognising any features that it has seen before and attacking them. This is acquired immunity. The other is an in-built system to battle with things it's not seen before, but which it knows to be an enemy - this is the innate immune system. The innate immune system needs receptors that will be able to recognise something is an invader without having seen it before, and this is achieved extremely well by Toll-like receptors.

The idea of Toll-like receptors is to spot any molecule which you will never find in the normal body (that is, the host), but which you might find on a bacteria. So, when a bacteria comes swimming by with weird molecules covering it, the Toll-like receptor spots that this isn't a normal molecule and starts the body's reaction to get rid of the invader.

The name for 'Toll-like receptor' is said to come from another receptor which was found in a fruit fly. This receptor was a big surprise to the original scientists who discovered it, so they shouted 'Great!' - but, because they were German, this was 'Toll!' The receptor was inevitably called the Toll-receptor, and because the topic of this article is similar in structure to the original, it is said to be like the Toll receptor - or, a Toll-like receptor. Clever, hey?

How do Toll-like receptors work?

Toll-like receptors usually sit on the surface of immune cells like macrophages or dendritic cells, also known as antigen presenting cells. These cells are placed around the body, ready to spot invaders, and deal with them appropriately when they do.

Imagine there's a bacterium - any bacterium - floating around. Most of the proteins (or antigens) on the surface will be different between different bacteria, and if the body tried to respond to them, it might accidentally attack its own proteins as well. However, some of the molecules - or ligands - which are on the surface of the bacteria are only found on bacteria. In fact, there will be certain molecules which are found on almost every bacteria, but not on any normal body cells.

These ligands are specific to invaders (or microbes), and these are the molecules which the Toll-like receptor will recognise. They include things like lipopolysaccharides found on the surface of bacteria; flagellin which is used to make the wavy flagellae that propel bacteria along; and double-stranded RNA, which you'll find in viruses but which the body doesn't naturally produce.

Different Toll-like receptors will recognise different examples of these ligands. However, when a particular Toll-like receptor recognises one, it will trigger a reaction in its cell. This might be phagocytosis (gobbling up the cell like a well-cooked meal!) so that it can break the invader apart into individual proteins and present them to T-cells - i.e. turning it into part of the acquired immune response. Alternatively, activation of the Toll-like receptor might lead to the production of cytokines - chemical messengers that trigger an immune response. The cells can also produce chemicals to try and attack the invader itself.

Basically the system works together to recognise a threat which it may never have seen before, but which contains tell-tale signs that it shouldn't be there. It's a bit like a zebra walking into the middle of a pride of lions. It's got signs that it doesn't belong to the group of lions, and as a result, the pride is able to mount a response against it - even if they've never seen a zebra before. Which means the body is extremely well-equipped to survive.

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