Klei T R, Enright F M, Blanchard D P, Uhl S A
Am J Trop Med Hyg. 1982 Mar;31(2):280-91. doi: 10.4269/ajtmh.1982.31.280.
Experiments were conducted to measure the degree of lymphatic pathology which develops in mongolian jirds (Meriones unguiculatus) sensitized to Brugia pahangi antigens prior to subcutaneous infections. Two protocols were used to sensitize jirds. One group of animals received three intravenous (IV) inoculations of 5,000 frozen, washed, B. pahangi-microfilariae at 10-day intervals. A second group received three inoculations of 150 micrograms of soluble somatic adult B. pahangi antigen (Ag) in Freund's complete adjuvant (FCA) at 10-day intervals. Groups of animals receiving saline in FCA and animals receiving no treatment served as controls. Following immunizations, animals from each group were tested for circulating antibody by the indirect hemagglutination assay, and for immediate and delayed hypersensitivity responses by the footpad swelling assay. All sensitized animals tested showed positive reaction to these assays. Observations at necropsy 90 days after inoculation with infective larvae showed that: 1) the percent recoveries of adult worms were the same in all treatment groups; 2) the numbers of patent infections which developed in the Ag in FCA-treated animals was greatly reduced; 3) level of microfilaremia which developed in animals sensitized with microfilariae was markedly lower; and 4) the degree of lymphatic pathology as judged by lesion score, numbers of intralymphatic thrombi, and lymphatic vessel size was significantly greater in presensitized animals than in nonsensitized infected controls. The increased lymphatic pathology seen in presensitized animals was most marked in jirds with occult infections and high antibody titers. These observations indicated that the B. pahangi-jird model is a useful semiquantitative system for the study of filarial-associated lymphatic pathology and strongly supports the hypothesis that the host immune response is involved in the pathogenesis of lymphatic filariasis.
进行了实验以测量在皮下感染前对彭亨布鲁线虫抗原致敏的长爪沙鼠(Meriones unguiculatus)中发生的淋巴病理程度。采用两种方案使沙鼠致敏。一组动物每隔10天静脉注射(IV)接种5000条冷冻、洗涤过的彭亨布鲁线虫微丝蚴,共接种三次。第二组动物每隔10天接种三次150微克可溶性彭亨布鲁线虫成虫体细胞抗原(Ag),佐剂为弗氏完全佐剂(FCA)。接受FCA中生理盐水的动物组和未接受治疗的动物作为对照。免疫后,通过间接血凝试验检测每组动物的循环抗体,并通过足垫肿胀试验检测即时和迟发型超敏反应。所有测试的致敏动物对这些试验均呈阳性反应。在接种感染性幼虫90天后进行尸检观察发现:1)所有治疗组成虫的回收率相同;2)FCA处理的动物中发生的显性感染数量大大减少;3)用微丝蚴致敏的动物中发生的微丝蚴血症水平明显较低;4)通过病变评分、淋巴管内血栓数量和淋巴管大小判断,预致敏动物的淋巴病理程度明显高于未致敏的感染对照。预致敏动物中增加的淋巴病理在隐匿感染和高抗体滴度的沙鼠中最为明显。这些观察结果表明,彭亨布鲁线虫-沙鼠模型是研究丝虫相关淋巴病理的有用半定量系统,并有力支持宿主免疫反应参与淋巴丝虫病发病机制的假说。