Some times the hidden or sequestered antigens get exposed to the circulating lymphocytes due to their release from inaccessible tissues such as central nervous tissue, testicular tissue, eye lens etc., either by accidental traumatic injury or surgery.
Exposure of sequestered antigens results in the stimulation of auto immune response leading to an autoimmune disease. For example, inflammation of the test is known as “orchitis” occurs in males followed by mumps. Since mumps virus damage the basement membrane of seminiferous tubules, leading to the release of sperms in to the circulation.
As the production of spermatozoa begins in puberty (at the age of 13 to 15), sperm antigens are not exposed to the developing immune system, hence immune system fails to develop tolerance to them.
Production of antibodies against sperm antigens takes place when sperm antigens enter in to the blood. The circulating antibodies enter the testis and initiates immune response.
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Inflammatory eye diseases also develop in the same manner. Antibodies produced against the lens proteins are responsible for the pathogenesis. The development of lens takes place around tenth week of gestation and thereafter they are isolated from fetal circulation.
Since the lens proteins are encapsulated prior to the development of immune system, they can not induce tolerance. Therefore if lens proteins escape into the circulation due to surgery or any other injury they induce production of antibodies against them resulting different inflammatory eye diseases and damage of lens.
The exact etiology of autoimmune diseases is not yet known. However, various theories have been offered. These include sequestered antigens, escape of auto-reactive clones, loss of suppressor cells, cross reactive antigens including exogenous antigens (pathogens) and altered self antigens (chemical and viral infections).