睾丸免疫豁免与天然免疫

Immune privilege and innate immunity in the testis

睾丸炎是引起男性不育的病因之一.睾丸是典型的免疫豁免组织,具有特殊的免疫调节机制.免疫豁免是指机体某些部位对外来抗原及自身抗原免疫反应很弱,以防止因免疫反应引起的组织损伤和功能紊乱.机体的免疫豁免位点包括睾丸、大脑、眼睛及孕期的子宫.睾丸的主要功能是产生精子与合成雄激素,而精子发生完成于机体免疫系统建立之后,在这一过程中,生殖细胞合成许多具有免疫原性的蛋白质.然而这些生殖细胞抗原在睾丸内并不诱导免疫反应,这主要是由于睾丸特殊的免疫豁免环境,睾丸免疫豁免受其组织结构、细胞特性及局部免疫抑制分子的共同调控.然而睾丸可以被多种病原体感染,为了克服免疫豁免环境,抵御入侵的病原体,睾丸建立了局部有效的天然防御机制.睾丸免疫环境平衡是维持其正常功能所必需的,睾丸免疫平衡受到破坏时,可引发睾丸炎,损伤男性生育能力.睾丸的免疫豁免与天然防御机制是广泛关注的科学问题,本文将综述这一领域的研究进展,提出亟待深入研究的方向.

Orchitis is one of the etiological factors of male infertility. The testis is a remarkable immune privileged organ and represents a special immunological environment. Immune privilege implies a small number of tissues in the body where allo- and auto-antigens are tolerated to prevent tissue damage and dysfunction by the systemic immune response. Immune privileged sites in mammals include the testis, brain, eyes and pregnant uterus. The two main functions of the testis are sperm production and androgen synthesis. Since the production of mature sperm occurs exclusively post-puberty, long after immune competence is established during fetal and early neonatal life, a large number of auto-antigens synthesized by germ cells are immunogenic. However, these germ cell auto-antigens do not induce immune responses within the testis, because of ＂immune privilege＂. Testicular immune privilege status is maintained by a combination of physical structures, testicular cell properties and local immune suppressive molecules. However, the testis can be infected by invading microbial pathogens. To overcome immune privilege and mount an appropriate local immune response to protect the testis from infection, tissue-specific cells have adopted effective innate immune functions against invading pathogens. Balance of the testicular immunological environment is necessary for tissue functions. Breakdown of immune homeostasis in the testis may lead to chronic orchitis, a significant etiological factor for male infertility. The mechanisms underlying testicular immune privilege and innate immunity are important issues in the field of reproductive biology. This review highlights the progress of studies on these issues, and outlines topics that are worthy of further investigation.