We have safeguards against developing immune responses against our own tissues. The first one, which was mentioned previously in this course is negative selection during T Cell and B Cell development. However, since not all self antigens are represented in the bone marrow or thymus, some self-reacting cells can escape into the circulation, but there are other mechanisms to prevent autoreactivity. One is that when self-reactive B or T cells encounter mono-valent antigen, a process occurs in the B or T cell that leads to anergy (meaning that the cell continues to live but does not function) in that cell. Also, one of the jobs of T reg (T regulatory) cells is to suppress self reactivity.
Despite all these safeguards, autoimmune diseases do develop, and are not uncommon. There are certain risk factors associated with development of autoimmunity:
- The dominant one is certain HLA/MHC types. Although this is not really a "cause and effect" situation, it is known that a high frequency of particular MHC types are found in certain autoimmune diseases. For instance, greater than 95% of people with Ankylosing Spondylitis (an autoimmune disease that attacks the spine) have the B27 molecule. However, not everyone that has this particular allele has Ankylosing Spondylitis. Over 80% of people with Type I diabetes have the DQ2 and DQ8 alleles. What one can deduce from this is that in certain people, these molecules present self antigen in such a way that induces reactivity.
- Female gender is another risk factor. More females develop diseases such as Addison's Disease, Systemic Lupus Erythematosus and many others. The reason for this is not fully understood.
- Trauma, especially to "immune privileged" sites, can induce autoimmunity. An example is an injury to the eye. Since immune cells generally don't access certain antigens from the eye, if there is injury to the eye releasing these antigens, an immune response can be induced.
- "Molecular Mimicry" is another mechanism. Some pathogens' antigens are so similar to some of the hosts' own antigens, and after the immune response to the pathogen has been induced, the immune cells then "cross-react" with self-antigens.
- Certain autoimmune diseases are also associated with environmental factors such as smoking.