Immune Systems of Long-lived Invertebrates

对生存的重要威胁之一是寄生虫的宿主，这些寄生虫感染所有有机体，导致疾病并威胁过早死亡。免疫系统是抵御寄生虫攻击的第一道防线。有效的免疫系统对长寿物种尤其重要，因为它们通常表现出从受孕到繁殖年龄的较长时间。免疫系统针对入侵的寄生虫，通常通过固定和直接对寄生虫进行细胞毒攻击的过程，也有结合和灭活入侵寄生虫的有毒产物的蛋白质。这项提案将描述长寿无脊椎动物--美洲马蹄蟹--免疫系统的不同元素，包括它的血液凝结系统和一个保护甲壳表面免受污染生物侵占的系统。(1)对于节肢动物和脊椎动物来说，血液凝块是免疫系统中一个被低估的组成部分。这项研究将调查免疫系统的一组蛋白质与血栓的纤维结合的潜在重要性。结合的免疫效应蛋白包括广泛反应的血浆蛋白酶抑制剂a2-巨球蛋白(A2M)，它可能起到保护纤维状血凝块免受被包裹的微生物蛋白降解的作用，以及一套其他针对有毒微生物产物(如脂多糖)的效应蛋白，并且对入侵的微生物具有直接细胞毒性。哺乳动物和节肢动物都利用血液凝块来固定寄生虫，减少它们全身传播的可能性。这项研究将检验这一命题，即凝块对入侵的微生物有直接毒性，并直接参与中和它们的有毒产物。这是一个全新的角度来看待血液凝块在免疫中的运作。(2)成虫如果有蜕皮的话，也很少蜕皮。然而，令人惊讶的是，甲壳没有固定的污垢有机体，这些污垢生物体装饰着与海水直接接触的其他固体表面。这个实验室已经确定了一种系统，它可能有助于保持成体角质层的原始特征，角质层是一层粘液层，从紧邻甲壳下面的腺体系统分泌到角质层表面。这种分泌物具有强大的细胞溶解活性，拟议的研究将表征真皮渗出物的细胞溶解活性，并表征该系统的保护功能。有可能的是，可以对使贻贝的甲壳不受污染生物的系统进行改造，以保护与海洋环境接触的人造表面免受污染物种的殖民。

One of the important threats to survival is the hosts of parasites that infect all organisms, causing disease and threatening premature death. The immune system is the first line of defense against attack by parasites. An effective immune system is particularly important for long-lived species because they typically show an extended period between conception and the age of reproduction. The immune system targets the invading parasite, typically by processes of immobilization and direct cytotoxic attack on the parasite and also has proteins that bind and inactivate toxic products of the invading parasites. This proposal will characterize distinct elements of the immune system of the long-lived invertebrate, the American horseshoe crab, Limulus polyphemus, including its blood clotting system and a system that protects the surface of the carapace from colonization by fouling organisms. (1) The blood clot is an under-appreciated component of the immune system for arthropods and vertebrates. The research will investigate the potential importance of the binding of a collection of proteins of the immune system to fibrils of the blood clot. Bound immune effector proteins include the broadly reactive plasma protease inhibitor, a2-macroglobulin (a2M), which may function to protect the fibrillar blood clot from proteolytic degradation by entrapped microbes, and a suite of other effector proteins that target toxic microbial products such as lipopolysaccharide and that are directly cytotoxic to the invading microbes. Both mammals and arthropods utilize the blood clot to immobilize parasites and reduce their potential for systemic dissemination. This research will test the proposition that the clot is, in addition, directly toxic to invading microbes and is directly involved in neutralizing their toxic products. This is an entirely new perspective on the operation of the blood clot in immunity. (2) The adult Limulus infrequently, if ever, molts its carapace. Nevertheless, the carapace is surprisingly free of the sessile fouling organisms that decorate every other solid surface in direct contact with seawater. This laboratory has identified a system that potentially contributes to maintaining the pristine character of the adult cuticle, a mucous layer secreted onto the surface of the cuticle from a system of glands that lie immediately beneath the carapace. This secretion has potent cytolytic activities and the proposed research will characterize the cytolytic activity of the dermal exudate and to characterize the protective functions of that system. It is possible that the system that keeps the carapace of Limulus free of fouling organisms can be adapted to protect man-made surfaces in contact with the marine environment from colonization by fouling species.