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利用实验性攻击模型对免疫绵羊肠道内蛇形毛圆线虫排斥过程中黏液和黏膜超敏反应作用的研究。

Studies on the role of mucus and mucosal hypersensitivity reactions during rejection of Trichostrongylus colubriformis from the intestine of immune sheep using an experimental challenge model.

作者信息

Harrison G B, Pulford H D, Gatehouse T K, Shaw R J, Pfeffer A, Shoemaker C B

机构信息

New Zealand Pastoral Agriculture Research Institute Ltd., AgResearch, Wallaceville Animal Research Centre, Upper Hutt.

出版信息

Int J Parasitol. 1999 Mar;29(3):459-68. doi: 10.1016/s0020-7519(98)00221-5.

Abstract

Nematode-naive sheep and sheep immunised by truncated infections with Trichostrongylus colubriformis were fitted with intestinal cannulae to allow administration of challenge infection and collection of intestinal fluids. Sheep were slaughtered at various times after challenge and the distribution of larvae along the small intestine was determined. Results showed that immune sheep had significantly fewer larvae in their intestines and that some sheep could expel the challenge infection within 2 h. Mucus samples from immune sheep contained increased parasite-specific antibody, histamine and anti-parasite activity as measured by larval migration inhibition assay. Higher levels of antibody and histamine were seen in intestinal fluids of immune sheep after challenge. Immunisation of sheep by truncated infections stimulated serum IgE and resulted in significantly higher numbers of IgE-positive cells in gut tissue sections before challenge and at 2 h and 24 h after challenge. Immune sheep also had greater numbers of mucosal mast cells and globule leucocytes after challenge, compared with naive sheep. When challenge larvae were mixed with mucus from immune sheep and infused back into naive recipient sheep, there was a distinct displacement of the larval population towards the distal part of the intestine, compared with the profile of larval establishment after infusion with mucus from naive sheep. These results are further evidence for an immediate hypersensitivity reaction in the intestine of immune sheep, where challenge larvae are expelled within 2 h and confirm the direct anti-larval properties of mucus. The cannulated-sheep challenge model described here will be a useful tool to unravel the mechanism of larval rejection from immune sheep and could lead to novel therapies.

摘要

对未曾接触过线虫的绵羊以及经短截型结肠毛圆线虫感染免疫的绵羊安装肠套管,以便进行攻击感染并收集肠液。在攻击后的不同时间宰杀绵羊,测定幼虫在小肠中的分布情况。结果显示,免疫绵羊肠道中的幼虫数量显著减少,部分绵羊能够在2小时内排出攻击感染的幼虫。免疫绵羊的黏液样本中寄生虫特异性抗体、组胺以及通过幼虫迁移抑制试验测定的抗寄生虫活性均有所增加。攻击后,免疫绵羊的肠液中抗体和组胺水平更高。经短截型感染免疫绵羊可刺激血清IgE产生,并导致在攻击前以及攻击后2小时和24小时,肠道组织切片中IgE阳性细胞数量显著增多。与未接触过线虫的绵羊相比,攻击后免疫绵羊的黏膜肥大细胞和球样白细胞数量也更多。当将攻击幼虫与免疫绵羊的黏液混合后回输到未接触过线虫的受体绵羊体内时,与输注未接触过线虫绵羊的黏液后幼虫定植情况相比,幼虫群体明显向肠道远端移位。这些结果进一步证明免疫绵羊肠道中存在速发型超敏反应,攻击幼虫可在2小时内被排出,并证实了黏液具有直接抗幼虫特性。本文所述的带套管绵羊攻击模型将成为揭示免疫绵羊排斥幼虫机制的有用工具,并可能带来新的治疗方法。

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