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Where in the body are self antigens important? In terms of central tolerance and autoimmunity, but also in terms of T cell activation?

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Could you clarify a bit? What do you mean by important? Most problematic? Most relevant? I assume the body you refer to is the human one? – terdon Dec 19 '13 at 11:33
This was a question in a PhD defense so I can only add my own interpretation. It's in the mouse and by important I mean anything really, relevant for proper development, where defects may lead to autoimmunity, and/or poor activation...I'm not entirely sure. – DunjaM Dec 19 '13 at 17:26

Self-antigens are not recognized by the body. This is due to self-antigens being presented to the immune system of the body during the embryological development. Any immune cell which recognize the pattern are destroyed during the intrauterine period, preventing the emergence of Auto-immunity in the Life-time.

Self-antigens become important in the following situations:

  1. There are self-antigens, called cryptic antigen, which are not presented to the immune system during embryologic development. These antigens generally are not present on the cell surface or they are present behind a barrier which is usually not penetrated by the immune cells. Eg.: The sperm antigens are not usually exposed to immune system as the sperms are behind the blood-testis barrier. Other such barriers are blood brain barrier, blood retina barrier, etc...

    • This is important because if for some reason (infection, trauma, etc...) such antigens get into the general circulation they will cause an immune reaction leading to autoimmunity
  2. Self antigens play a role in graft rejection and transfusion reactions. This is mediated specially by the T-cells. This is the reason why transplant patients receive life-long immune supressants and cross-match is done before transfusion

  3. Self-antigen non-recognition also means non-self antigen recognition. This is the basis of cells infected with viruses or tumor cells getting destroyed. As the new protein peptides (viral or mutated regular proteins) presented by the MHC 1 are not recognised as self, such cells are destroyed protecting the body

  4. The corollary of 3 is that any pathogen which resembles the self-antigen are tolerated and active immunity does not come into play i.e. the epitopes that are recognized as self do not cause any immune response

  5. Some pathogens have antigens that closely resemble human antigens. When T-cells mount response against such antigens, a specific sub-clone of T-cell or B-cell (which are activated by the T-cell) may gain the ability to act against the body cells (due to mutations in the hotspots of the anti-topes) that have antigEns resembling the pathogens. This is called molecular mimicry. A well established disease that is due to this mechanism is the Rheumatic Heart Disease. Post-streptococcal Glomerulonephritis is also another example.

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That is the old model of the immune system. There are many other models, which are closer to the reality. E.g. many self recognizing cells become regulating cells instead of dying, and a lot of non self cells (microbes) can be tolerated by the immune system until they don't cause cell death and other messy things... By auto immunity, not just the molecular mimicry is the problem, e.g. a single T cell can have different receptors, so one of the receptors can be self recognizing, while the others can recognize a pathogen, and so on... Immunology is very complicated... – inf3rno Jan 7 '15 at 1:11
1 :-) I have the same problem, I read mostly reviews and scientific articles, probably dissertations if have more time. I don't know of a book which is up to date. E.g. none of the ones I checked, mention gasotransmitters, which is a relatively new topic in immunology. Wikipedia is often incomplete, or sometimes even completely wrong. I'll try to make an own wiki, but I have too many tasks: developing programming framework, learning stock exchange indicators, learning data mining, learning immunology, making training plans, etc... 24h in a day is simply not enough. :S – inf3rno Jan 7 '15 at 1:55
Please let me know if you've found a book worth to read! – inf3rno Jan 7 '15 at 1:55
1 Be aware that wikipedia is not a reliable scientific resource, so if you want to learn this in depth, you have to find scientific articles and reviews in the topic. – inf3rno Jan 7 '15 at 1:58
Ohh sorry :D (was redirected automatically by google) – inf3rno Jan 7 '15 at 12:47

There can be many responses. They are important for alloimmunity (so by transfusion, transplantation, etc...), for recognizing pathogens, cancer, virus, etc... By T cell activation, the regulator T cells recognize these antigens as self, and prevent the autoimmune reaction.

I guess they were thinking on MHC1 and MHC2. MHC1 shows the inside of the cells, so e.g. by viral infection or cancer non-self oligopeptides (from degraded proteins) bind to MHC1. These non-self antigens are recognized by CD8+ T cells, which destroy the affected cells. MHC2 is used by APCs to present possible pathogens to CD4+ T cells in a similar way.

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