ROLE OF SANDFLY SALIVA IN LEISHMANIASIS

利什曼原虫通过叮咬传播给它的哺乳动物宿主 血吸虫沙蝇。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虫。豁免权 利什曼病似乎是由于巨噬细胞的精化。 由寄生虫特异性T细胞激活的因子，使 巨噬细胞来破坏它的寄生虫负担。然而，它是， 令人惊讶的是，自从利什曼病以来，这种特定的豁免权是必需的 可容易地被宿主非特异性免疫力量破坏(例如， 补体)，在巨噬细胞内，寄生虫必须以某种方式 在吞噬小体的恶劣环境中生存。一部份 这个谜团的答案已经通过萨克斯和 同事们描述了利什曼原虫的后循环形式， 在沙蝇体内发育，更能抵抗 补体和巨噬细胞。然而，后环寄生虫是 仍然不能完全抵抗这两种宿主防御 机械装置。因此，寄生虫很可能有其他途径 从而逃避这些最初的非特定宿主防御 特异性T细胞的作用机制及后期攻击 豁免权。 当沙蝇叮咬哺乳动物宿主时，它会流口水进入 皮肤。苍蝇的唾液含有许多强效成分 药理活性，最近在 申请人实验室发现沙蝇唾液显著增强 利什曼原虫对小鼠具有感染性，并阻断巨噬细胞的激活。 因此，检查唾液对人体健康的影响就变得很重要。 利什曼原虫和巨噬细胞上的各种沙蝇 功能。这些研究将在两个生化系统上进行 和分子水平，并可能导致对小说的描述 免疫调节的形式。这些实验还将尝试 鉴定和分离在沙蝇体内发现的各种活动 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 在哺乳动物中开始感染利什曼原虫 宿主，如果它的活性被中和，感染将是 被阻止了。因此，动物将用唾液免疫，或者 其相关成分，试图接种疫苗 利什曼病。

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.