As far as I understood so far, B and T cells are produced in the bone marrow, and during their maturing process in the bone marrow or Thymus, the are "programmed" to react to certain proteins. It is like giving them a particular key.

As I also understood, these "keys" are entirely created by random. Which means, that also "keys" are generated that match cells of the "host body." Hence, if released into the bloodstream/lymph system, those B and T cells would attack the cells of the "host body."

As I understood further, there is a kind of a "security system" which checks if B and T cells are produced that would attack cells of the "host body." This security system would intervene and destroy those B and T cells before they are released into the bloodstream/lymph system.

As read lately - and I am not sure if I did understand this correctly - it is also possible, that B and T cells could also react to other cells even if the key doesn't match perfectly.

Now my questions.
Firstly, being an SW engineer interested in this topic is my understanding above correct?

Secondly, is it correct to say that autoimmune diseases are mainly caused by the following two points: 1. the "security system" in the bone marrow / Thymus failed, and therefore "bad" B and T cells were released into the bloodstream/lymph system
2. B and T cells react to other cells, even if the "key" does not match perfectly.

  • $\begingroup$ Welcome to Biology.SE! You need to keep in mind that this is one of the (many) riddles in biology which aren't completely solved yet. So, although you might get answers to many of your questions, don't expect an answer to everything $\endgroup$ Jun 4 '17 at 17:26
  • $\begingroup$ This will be a fun read for you. Note the publishing date: this is still a hot area of debate. Also note that there's another security system, clonal anergy, meant to stop rogue cells from responding to autoantigens: T cells require 2-3 signals during Ag stimulation for conventional activation, as do B cells require Th or Tfh cell co-stimulation. Otherwise they're made to become quiescent and die in the periphery. $\endgroup$
    – CKM
    Jun 4 '17 at 17:47
  • 1
    $\begingroup$ There's also this notion that B or T cells regularly need to get survival signals, often times from very weak self-pMHC signalling that doesnt activate them, but says stay alive (ref). Whats interesting about B and T cell maturation is they need enough binding for self-pMHC at selection checkpoints that they don't bind too tightly, but also that they bind at all. $\endgroup$
    – CKM
    Jun 4 '17 at 17:50
  • $\begingroup$ Consider you're a software engineer, consider an autoimmune disorder the equivalent of a bad antivirus update causing your AV to recognize C:\Windows\system32 as a threat and "quarantine" it. $\endgroup$ Jun 15 '17 at 13:55

Your understanding of the process is basically correct. There are of course a lot more details to it, but that wouldn't be in the scope of the question. Do note that only T cells mature in the thymus (that's where the T comes from ^^), whereas B cells mature in lymph nodes and the spleen.

As for why autoimmunity occurs you also understood the basics, however the devil is in the details: wikipedia does have a much longer list of mechanistically different causes. While its often sufficient to explain immune recognition using 'keys' (T cell receptor / B cell receptor = antibody) and their respective 'locks' (peptides bound to MHC / antigens), the exact process of immune cell activation becomes important in autoimmunity, where cells are wrongly activated. This means that there are many possible points at which the 'security system' of the immune cell maturation can (or rather has to) fail to allow autoimmunity.

As for the cross-reactivity of cells: the difference between the binding of B cells (via antibody/B cell receptor to protein surfaces) and T cells (via T cell receptor to peptide sequences) means that in general T cells are much more likely to show cross reactivity - just because the possibility space of a 10-12aa peptide is much smaller than that of a protein surface (even though the probability is still very low).

Additionally - as stated in the comments to your question - both the immune activation pathway and the issue of cross reactivity, while principally understood, are not 'completely solved'. The immune system is insanely complex just by itself and the addition of interactions with both almost all human proteins AND proteins any kind of pathogen, mean that it will take quite a lot of time until researchers can figure out all the weird quirks caused by the 'wrong' combinations.


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