I was doing some reading about anti-sperm antibodies (ASA) - antibodies produced against sperm if sperm accidentally gets into the bloodstream, such as via testicle injury or whatnot - and apparently such ASAs might only reduce your fertility somewhat, or can make you all but infertile - there’s a wide range of what it will do to you.
This surprised me since I thought antibodies are basically produced to kill everything of something. If you have a cold, for instance, won’t your body keep producing antibodies until it detects no more cold viruses in the body? So I wondered, as long as you have sperm in your body (even in the testicles or vas deferens where it belongs,) once your body has decided to go anti-sperm and produce ASAs, won’t it keep manufacturing them until you are totally sterile?
That was a mistaken thought, especially in the context of what are called “autoantibodies” - antibodies against parts of self. The antibody response working in conjunction with the rest of the immune system, is often enough to clear cold viruses and the like, but often the response is not, be it against non-self (chronic Hepatitis B or C infection, HIV, HPV …) or self (auto-immune thyroiditis, celiac disease, diabetes, etc.).
The main part of the picture that you’re missing is that the testes are an immune privileged site. In some parts of the body, T-cells are excluded by a physical barrier, or through other mechanisms the immune response is suppressed.
Mature sperm are not present early in life when the adaptive immune system learns tolerance for “self” antigen. That’s why the testes need to be an immune privileged site - sperm would otherwise always be perceived as non-self and produce an adaptive immune response.
So that’s why anti-sperm antibodies usually only develop when sperm infiltrate somewhere they shouldn’t be inside the body, such as the bloodstread. And the immune privileged status of the testes is the reason that these antibodies will still not mount a full-fledged reaction against sperm inside the testes.
So Riemann, parts of the body subjected to auto-antibodies that are not similarly immune privileged are all subject to full fledged reactions that completely destroy the organ involved?
No, we are not seeing a full immune response in most autoimmune disease, but for different reasons. Other autoimmune diseases are not quite the same, in the sense that they affect tissues for which there should be tolerance as “self”, since the tissue was present when central tolerance was established. Our understanding of why most autoimmune diseases occur is partial at best.
Mature sperm are unusual in that they are not present in the body when central tolerance is established, so they do require special treatment. Anywhere outside of the priviliged site of the testes, I believe sperm do generate just as strong a response as you’d get with a truly foreign antigen.
The point is to correct the op’s misperception that antibody response is “and all or nothing thing”. It is not. Including to non-self in which long term stalemates sometimes occur.
As to the specific of sperm … you seem to be saying that the level of anti-sperm antibodies in those who have it are much higher than the levels of anti-thyroid antibodies, etc., (due to a lack of exposure when central tolerance was formed), and that the lack of complete infertility is exclusively because of its protected location status … I am honestly doubtful of that claim. Do have any sources for relative antibody levels? Even the protected location seems to be questionable as anti-sperm antibodies are found in the semen.
I’m not disputing that, very little in biology is all-or-nothing. I simply pointed out that the testes are an immune privileged site, which is the most important factor in this case in limiting the immune response.
T-cells and antibodies are not excluded from the testes, immune privilege involves other processes than just physical barriers and exclusion to suppress the immune response. And obviously there is some immune response taking place, or presumably there would no effect on fertility.
I linked above to the Wikipedia article on testicular immunology, which discusses what we know quite extensively, well beyond both of our levels of expertise. If you want to dispute what it says there… you will have to find an expert immunologist.
Programmed Cell Death is a mechanism that dampens the immune system response and is important in regulating and preventing autoimmune disorders.
When I was given a PD-1 inhibitor (as part of a chronic viral disease treatment trial), the following inflammatory response markers could have been an autoimmune reaction triggered by the PD-1 inhibitor - instead, it was evidence that my immune system was fighting the virus for harder and longer than previously, and my immune system was able to clear the viral illness after decades of stalemate.