sameeralord said:
Hello everyone,
What I just read is for type 1 diabetes mellitus, it requires an environmental factor (eg virus) and genetic determinant that allows the B cells to be detected as non self. Now I'm not very familiar with autoimmune diseases.
My question is why does a virus have to come and trigger the autoimmune destruction of B cells. If B cells are alreadly genetically non self, shouldn't the body start attacking them without a stimulus? Thank you
Well it gets real complicated real fast, but here's the short version of it.
Your specific immune response works by recognition of "self" and "not-self". This is carried out by a class of molecules we call MHC II (major histocompatability complex). Which present an antigen or epitope to immune cells.
When you are born, T-cells and B-cells (the main stay of your specific immune response) undergo recombination events for their MHC II receptors, theoretically then you get every possible combination of antigen or epitope.
The flaw here is that you would also make T/B-cells against
your own antigens.
How does the body get around this? By sending T-cells and B-cells to "school". T-cells go to T cell school in the thymus, while B cells do so in the bone marrow. They get "educated" (literally what immunologists call it) so they don't go all crazy on "self".
The problem is that binding an antigen isn't "perfect". Its less like an exact puzzle fit and more like a being able jam something through wet cardboard.
Some of your T/B-cells then will have "learned" not recognize self, but still have MHC II receptors that can bind to sufficiently similar "self" antigens.
In an autoimmune response that is primed by a pathogen, that pathogen has antigens which not only fit the MHC II receptor of the T/B-cells, but also resemble (closely enough) some of your own antigens/epitopes.
When the immune system gets primed against these pathogens, the cells (T/B) proliferate. They make two kinds of cells, effectors (which go out and kill stuff) and memory (which "store" an immune response for future invasion).
The problem then arises when you get lots of these clones which can also bind the "almost-self" antigen. Even after the pathogen is gone, these cells (memory mostly) start to roam the body in search of the specific pathogen they are primed against. When they find something that "almost-fits" (like say you pancreatic B cells) they start a immune response, by proliferating and attacking. Unfortunately, they've forgot their schooling and destroy things labeled "self".
And it just keeps getting worse, because the more of the "almost-self" they find, the more they proliferate and attack.
Also, type 1 diabetes is a lack of insulin. Which can occur a couple of ways, one would be by a heritable mutation. Another, as you suggest is an autoimmune response to pancreatic b cells. Also, it is conceivable that pathogen primes B lymphocytes to make antibodies against insulin. Which would get bound up by antibodies (we call this opsonization) and destroyed by phagocytic cells.
Does that help?
Edit: There's also another class of MHC proteins called MHC I (creative right?) which work mostly by the stimulation of cytotoxic-T cells (this is especially important for viral responses). Another class of immune cells, NK cells (natural killer) destroys cells that don't have enough MHC ligands on their surface (in case anyone is trying to "sneak by"), which is especially important for cancer cells.
