Ruslan Medzhitov and discovery of Toll-like receptors; Nobel Prize ignored him
youtube.com
youtube.com
Here is my layman interpretation (disclaimer: I am not by any means knowledgeable in biology, and just wikepidyed most of the terms used):
1) our immune system has T cells that are responsible for recognizing if an antigen is 'foreign' molecule/substance or something that's generated by our own body (self).
These types of T-cells are called 'Regulatory T-Cells' [1]
2) Cancers, as an example, trick these types of cells to think that the cancerous cells are 'self'
3) For these type of regulatory T-Cells (T-regs) to get activated, they need 2 signals:
-a- signal that says -- here is a pathogen
-b- signal that says -- this pathogen is foreign (if not, immune system will not get activated).
Toll-like receptors help with -b-.
They work, in a way (this is my analogy, sorry if it is lame), like RegEx (regular expression), that have evolutionary encoded patterns that indicate the origin of a given antigen. And that's the core of Ruslan Medzhitov's research
4) So if we get the regex match of the antigen structure (which is being sliced 'prepped up' for the check, by slicing its proteins into peptides) -- the signal 2 is generated, and immune system will activate.
If the match did not happen -- no activation.
5) Another interesting thing, (or may be I misunderstood) Is that those TReg cells, each do not have 'all the patterns'. Instead, our body generates, randomly, many of those cells, and each one just have one of those 'RegEx'. So another key, is that our body has to, in parallel, so to speak, apply multiple of them to the foreign body. And so some of those TReg cells would never get activated (as they did not have the pattern to induce the -b- signal). But others, hopefully, would get the match and the -b- signal will happen, and immune system will get activated.