Corbeil L B, Anderson M L, Corbeil R R, Eddow J M, BonDurant R H
Department of Pathology, University of California, San Diego Medical Center, California 92103-8416, USA.
Am J Reprod Immunol. 1998 Mar;39(3):189-98. doi: 10.1111/j.1600-0897.1998.tb00353.x.
Mechanisms of protective immunity in the female reproductive tract are poorly understood. For sexually transmitted diseases, bovine trichomoniasis is a useful model because it resembles human trichomoniasis to some extent, and antibodies play an important role in protection against these extracellular parasites. Protective efficacy was compared in animals with genital responses of predominantly immunoglobulin G (IgG) or predominantly IgA antibodies to a purified surface antigen of Tritrichomonas foetus.
Immunization of mice by various routes with immunoaffinity-purified T. foetus surface antigen (TF1.17) or killed cells was used to define the best routes and antigen combinations to give predominantly IgG or IgA antibodies to TF1.17 antigens in genital secretions. Cattle were then immunized either subcutaneously (SC) two times with TF1.17 antigen and once SC with killed T. foetus or twice SC with TF1.17 antigen and once intravaginally with killed T. foetus. All immunizations were in Quil A adjuvant. Controls were not immunized. Animals were challenged intravaginally with 10(6) T. foetus 3 weeks after the third immunization. Vaginal mucus was collected weekly for culture and antibody assays. Serum was collected weekly, and uterine secretions were collected at 10 weeks post-challenge. Tissues were fixed at 10 weeks also.
Murine studies showed systemic priming with vaginal boosting gave the highest genital IgA responses. In cattle, systemic immunization (group S) induced high IgG1 antibody levels in vaginal secretions. Systemic priming with vaginal boosting (group S/V) primed for an anamnestic vaginal IgA response after challenge with T. foetus. Cattle with predominantly IgG or predominantly IgA responses in vaginal secretions either did not become infected or cleared infection faster than controls. Uterine IgA responses at 10 weeks were highest in the vaginally boosted group, but other responses were not different from the controls at this time point. Microscopic examination of genital tissues showed subepithelial infiltration of mononuclear cells in all groups. Lymphoid aggregates or nodules were detected in vaginal sections in cattle of groups S/V and C as well as in uterine sections of all animals in all three groups.
Both IgG and IgA antibodies to T. foetus superficial antigen were associated with protection. The timing of the response was related to the time of clearance. Lymphoid organization in the vagina and uterine tissues suggested development of mucosal inductive sites.
女性生殖道保护性免疫的机制尚不清楚。对于性传播疾病而言,牛毛滴虫病是一个有用的模型,因为它在一定程度上类似于人类毛滴虫病,并且抗体在抵御这些细胞外寄生虫的过程中发挥重要作用。比较了对胎儿三毛滴虫纯化表面抗原主要产生免疫球蛋白G(IgG)或主要产生IgA抗体的动物的生殖器反应中的保护效果。
通过多种途径用免疫亲和纯化的胎儿三毛滴虫表面抗原(TF1.17)或灭活细胞免疫小鼠,以确定在生殖器分泌物中产生针对TF1.17抗原的主要为IgG或IgA抗体的最佳途径和抗原组合。然后,用TF1.17抗原对牛进行两次皮下(SC)免疫,并用灭活的胎儿三毛滴虫进行一次皮下免疫,或者用TF1.17抗原进行两次皮下免疫,并用灭活的胎儿三毛滴虫进行一次阴道内免疫。所有免疫均使用Quil A佐剂。对照组未进行免疫。在第三次免疫后3周,用10⁶个胎儿三毛滴虫对动物进行阴道内攻击。每周收集阴道黏液进行培养和抗体检测。每周收集血清,在攻击后10周收集子宫分泌物。在10周时也对组织进行固定。
小鼠研究表明,全身初免加阴道加强免疫产生的生殖器IgA反应最高。在牛中,全身免疫(S组)在阴道分泌物中诱导出高IgG1抗体水平。全身初免加阴道加强免疫(S/V组)在受到胎儿三毛滴虫攻击后引发了记忆性阴道IgA反应。阴道分泌物中主要产生IgG或主要产生IgA反应的牛要么未被感染,要么比对照组更快清除感染。在10周时,阴道加强免疫组的子宫IgA反应最高,但此时其他反应与对照组无差异。对生殖器组织的显微镜检查显示,所有组均有单核细胞的上皮下浸润。在S/V组和C组牛的阴道切片以及所有三组所有动物的子宫切片中均检测到淋巴滤泡或结节。
针对胎儿三毛滴虫表面抗原的IgG和IgA抗体均与保护作用相关。反应的时间与清除时间有关。阴道和子宫组织中的淋巴组织形成表明黏膜诱导部位的发育。