ROLE OF SANDFLY SALIVA IN LEISHMANIASIS

利什曼原虫通过叮咬传播给哺乳动物宿主， 白蛉 在哺乳动物宿主中，利什曼原虫是 巨噬细胞的专性细胞内寄生物。 豁免权 利什曼病似乎是由于巨噬细胞的加工 寄生虫特异性T细胞激活因子， 巨噬细胞破坏其寄生虫负担。 然而， 令人惊讶的是，这种特异性免疫是必需的， 可以容易地被宿主非特异性免疫力破坏（例如， 在巨噬细胞内，寄生虫必须以某种方式 在吞噬溶酶体的恶劣环境中生存。 部分 这个谜的答案已经由萨克斯的工作提供， 他的同事描述了利什曼原虫的亚循环形式， 在沙蝇中发展，并且更耐降解， 补体和巨噬细胞。 然而，亚循环寄生虫 对这两种宿主防御都没有完全抵抗力 机制等 因此，寄生虫很可能有其他手段 通过这种方式，它可以避开这些最初的非特异性宿主防御， 机制以及后来的特定T细胞的攻击 免疫力 当沙蝇叮咬哺乳动物宿主时，它会向 皮肤 苍蝇的唾液中含有大量的 药理活性，最近在 申请人的实验室证实沙蝇唾液显著增强了 利什曼原虫对小鼠的感染性和阻断巨噬细胞活化。 因此，检查唾液对人的影响变得很重要。 利什曼原虫和巨噬细胞上的各种白蛉 功能协调发展的 这些研究将在生物化学 和分子水平，并可能导致新的描述 免疫调节的形式。 这些实验还将试图 描述和分离白蛉中发现的各种活动 唾液，以确定每种物质的作用方式。 最后，在自然界中，沙蝇的唾液可能是至关重要的 利什曼原虫在哺乳动物中的感染开始 宿主，而且，如果它的活性被中和，感染将被 防止。 因此，动物将用唾液免疫，或 其相关成分，以试图接种疫苗， 黑热病

Leishmania is transmitted to its mammalian host by the bite of phlebotomine sand flies. Within the mammalian host, Leishmania is an obligate intracellular parasite of macrophages. Immunity to leishmaniasis appears to be due to the elaboration of macrophage activating factors by parasite specific T cells which allow the macrophage to destroy its parasite burden. It is, however, surprising that this specific immunity is required since Leishmania can be readily destroyed by host non-specific immune forces (e.g., complement) and, within the macrophage, the parasite must somehow survive in the hostile environment of the phagolysosome. A partial answer to this enigma has been supplied by the work of Sacks and colleagues who described metacyclic forms of Leishmania which develop in the sand fly and are more resistant to degradation by complement and macrophages. However, the metacyclic parasites were still not completely resistant to either of these host defense mechanisms. Therefore, the parasite is likely to have other means by which it evades these initial non-specific host defense mechanisms as well as the later onslaught of specific T cell immunity. When the sand fly bites the mammalian host, it salivates into the skin. The saliva of the fly contains a number of potent pharmacological activities and it has recently been shown in the applicant's laboratory that sand fly saliva dramatically enhances Leishmania infectivity for mice and blocks macrophage activation. It therefore becomes important to examine the effect of saliva from various species of sand flies on Leishmania and on macrophage functions. These studies will be performed on both a biochemical and molecular level and could result in the description of novel forms of immunoregulation. The experiments will also attempt to characterize and isolate the various activities found in sand fly saliva in order to determine the mode of action of each substance. Finally, it is possible that in nature sand fly saliva is critical to the initiation of infection with Leishmania in the mammalian host, and, if its activity were neutralized, infection would be prevented. Therefore, animals will be immunized with saliva, or the relevant components thereof, in an attempt to vaccinate against leishmaniasis.