犬钩虫第三期钩蚴免疫裸鼠再感染AcL3的组织病理学观察

Pathomorphology observation on nude mice immunized and challenged with third-stage infective hookworm （ Ancylostoma caninum ） larvae

目的观察裸鼠经犬钩虫第三期钩蚴（AcL3）免疫后，其皮肤和肺内AcL3的形态变化及宿主的组织细胞反应，评价其作为疫苗筛选动物模型的可能性。方法取BALB／c-nu／nu小鼠，每两周由皮下免疫接种活的AcL3 500条，共3次，并于末次免疫后1周由皮肤攻击感染AcL3 500条。用未免疫的感染AcL3裸鼠作对照，攻击感染后不同时间取感染部位皮肤和肺脏，观察宿主皮肤和肺内AcL3的组织病理学变化。结果攻击感染后6、24、72h及7d，皮肤内的绝大部分虫体切面形态和组织结构与感染对照裸鼠皮肤内的相似，仅0．5％～2．2％的虫体切面示有变性、死亡，偶见有死虫肉芽肿，而肺组织内的AcL3及其周围的炎细胞反应与对照组相比较，无明显差异。结论用活的AcL3免疫裸鼠后，仅见对攻击感染的AcL3有弱的免疫效应，裸鼠不适宜作为钩虫疫苗筛选的动物模型。

Objective To observe the inflammatory responses and morphology changes in the lung and skin of nude mice immunized and challenged with third stage hookworm larvae of Ancylostoma caninum （ AcL3 ）, and then, to investigate the feasibility of nude mice as vaccine screening animal model. Methods Nude mice BALB/c-nu/nu were immunized subcutaneously with three doses of 500 AcL3 at 2-week intervals, and then challenged percutaneously with 500 AcL3. Lungs and skins were excised from post-challenged nude mice after 6, 24, 72 h and 7 d, and then examined by light microscopy. Non-immunized nude mice served as negative controls. Results In both non-immunized mice and majority of immunized mice, the AcL3 exhibited no structural damage and infiltrating inflammatory cells were absent at the surrounding tissues. There were no changes in the architecture of skin and lung tissues. However, about 0.5%-2.2% AcL3 in the skin of immunized mice exhibited cuticular swelling, damage and even death, and the surrounding tissue was infiltrated by polymorphonuclear inflammatory cells. From 24 h to 72 h post-challenge, granulomata were observed surround- ing the dead AcL3. Conclusion Weak post-vaccination host immune response against challenged AcL3 was seen in nude mice, indicating that it was unsuitable to be used as vaccine screening animal model.