Sperm & testicular autoimmunity – The human immune system is trained during the early postnatal period. In men, at puberty when the sperm first appear in the testis and epididymis, the human immune system will have the chance to contact sperm antigens. Similarly, when women become sexually active, their immune system will inevitably contact sperm antigens. Therefore, once sperm, as an autoantigen, activates the human immune system, an autoimmune response against human sperm will occur. The blood-testis barrier and the epididymal blood-epithelium barrier in humans are important structures in preventing sperm antigens from contacting immunocompetent cells, due to the tight junctions of Sertoli and epithelial cells. This creates favorable conditions for spermatogenesis and sperm survival in the testicular fluid, and sperm maturation in the epididymal fluid. It also prevents the occurrence of autoimmunity after puberty. Therefore, alteration of the blood-testis barrier and the blood-epithelium barrier allows the production of ASAs and, hence, may lead to infertility. There are three types of sperm autoimmunity: that associated with genital tract obstruction, that accompanied by tesricular inflammation, and a spontaneously occurring type that does not present with either of the preceding associated features.