MACROPHAGE ACTIVATION IN EXPERIMENTAL LEISHMANIASIS

巨噬细胞活化的实验研究进展 利什曼病将试图定义巨噬细胞的作用 Ia在遗传敏感和抗性反应中的作用 品系的小鼠对利什曼原虫有重大感染。鉴于 BALB/c小鼠发生内脏致命感染， 被用作弥漫性皮肤和皮肤的实验模型 系统性利什曼病在人类中，C57B1/6小鼠对 病情严重，随病情发展完全康复 局部损伤。不同免疫反应的原因 对这两个品系小鼠体内的寄生虫的了解还不是很清楚 但可能与易感的Balb/c的趋势有关 小鼠承受不适当的、非保护性的扩张 感染后T淋巴细胞的变化。T细胞的这种扩增 显然会导致无法控制或产生免疫力 寄生虫，一种由各种不同的事实证实的理论 包括预防性环孢素在内的免疫调节策略 一种治疗方法允许保护和发展 在易感小鼠模型中对主要乳杆菌的免疫力。AS 淋巴细胞可被激活的Ia刺激扩张 巨噬细胞，可能是这些细胞的过量 刺激巨噬细胞在感染期间被激活 非免疫抑制、感染的Balb/c小鼠。事实上，初步的 数据显示腹膜渗出物中含有很高水平的Ia 与未感染的Balb/c小鼠相比，感染的Balb/c小鼠确实有细胞发育 受感染的对照组。 希望这项研究将有助于澄清激活的作用 巨噬细胞对L. 以及它们与疾病进程的关系。具体地说， 豚鼠腹膜腔内含Ia的巨噬细胞水平 C57B1/6、Balb/c和环孢素治疗的Balb/c小鼠 比较感染后不同时间的变化。此外, 受感染的Balb/c小鼠将接受Ia抗体预防性治疗 抗体，以便进一步分析可能的 巨噬细胞活化在系统性红斑狼疮中的免疫调节作用 疾病的发展。所有动物都将被跟踪检查是否有疾病 通过确定病变大小在每个时间点进行进展， 引流淋巴结和脾的细胞数和重量， 利什曼原虫对脾和淋巴结的转移及其水平 抗利什曼抗体与迟发型超敏反应 一种利什曼病毒抗原。

The proposed study on macrophage activation in experimental leishmaniasis will attempt to define the role of macrophages bearing Ia in the response of genetically susceptible and resistant strains of mice toward Leishmania major infections. Whereas Balb/c mice develop visceralizing, fatal infections which have been used as experimental models both for diffuse cutaneous and systemic leishmaniasis in man, the C57B1/6 mice are resistant to severe disease and recover completely following the development of local lesions. The reasons for the different immune responses to the parasite in these two strains of mice is not well understood but may be related to the tendency of the susceptible Balb/c mouse strain to undergo an inappropriate, nonprotective expansion of T lymphocytes following infection. This expansion of T cells apparently leads to the inability to control or develop immunity to the parasite, a theory substantiated by the fact that various immunomodulatory strategies including prophylactic cyclosporine A treatment allows for protection and the development of immunity against L. major in the susceptible mouse model. As lymphocytes may be stimulated to expand by activated, Ia bearing macrophages, it may be that an over-abundance of these stimulatory macrophages become activated during infection in non-immunosuppressed, infected Balb/c mice. Indeed, preliminary data has shown a very high level of Ia-bearing peritoneal exudate cells does develop in infected Balb/c mice as compared to non- infected controls. It is hoped that this study will help to clarify the role of activated macrophages in the susceptibility or resistance of mice to L. major and their relation to the disease process. Specifically, the levels of Ia bearing macrophages of the periotoneal cavities of C57B1/6, Balb/c and cyclosporine treated Balb/c mice will be compared at different times following infection. In addition, infected Balb/c mice will be prophylactically treated with anti-Ia antibody in order to further analyze the possible immunoregulatory role of macrophage activation in systemic disease development. All animals will be followed for disease progression at each time point by determinations of lesion size, cell numbers and weights of the draining lymph node and spleen, metastasis of Leishmania to the spleen and lymph node and levels of anti-leishmanial antibodies and delayed type hypersensitivity toward a leishmanial antigen.