Humoral Immunity of Long-lived Invertebrates

MCB 9726771 Armstrong，Peter Quigley，James长寿无脊椎动物的体液免疫 通俗摘要 任何动物的生存都需要有效的手段来阻止无数不同潜在病原体的入侵。 因此，大多数动物进化出各种不同的防御策略来保护自己。 这些包括哺乳动物非常复杂的适应性免疫系统以及较不复杂的先天防御机制，这些机制经常出现在低等动物中。 本研究的重点是无脊椎动物的一个特殊的防御系统，并利用美国鲎（美洲鲎）作为一个模式系统。 这种动物缺乏作为适应性免疫系统核心要素的抗体和淋巴细胞，但其血液系统中具有提供对病原体的抵抗力的成分。 一个系统涉及血浆蛋白，β-巨球蛋白，它能够结合到血液中的微生物蛋白酶。 不仅结合的β-巨球蛋白抑制蛋白酶，而且血细胞也识别、去除和降解由此形成的复合物。 第二个系统涉及第二种血浆蛋白，鲎素，它具有结合并溶解进入血流的外来细胞的能力。 这两个系统在功能上是相互关联的，因为蛋白酶反应的β-巨球蛋白可以增强鲎素的溶解活性。 目前的研究包括三个目标，以确定这些系统的基本特征。 (1)血细胞上结合蛋白酶-β 2-巨球蛋白复合物的受体将被分离和鉴定。 (2)将描述影响细胞摄取复合物的结合和途径的因素。 (3)蛋白酶-β 2-巨球蛋白复合物和其他因子调节鲎素溶解活性的分子机制将被确定。 这些研究不仅能让我们了解鲎中的这些系统，而且还可能预测在更复杂的高等生物的B细胞中发现的相关蛋白质的类似功能。

MCB9726771 Armstrong, Peter Quigley, James Humoral Immunity of Long-lived Invertebrates Lay Abstract Survival of any animal requires efficient means to thwart the invasion of a myriad of different potential pathogens. As a result, most animals have evolved a variety of different defense strategies for their protection. These include the very complex adaptive immune system of mammals as well as less complex, innate defense mechanisms represented frequently in lower animals. The present research focuses on a particular defense system of invertebrates and utilizes the American horseshoe crab (Limulus polyphemus) as a model system. This animal, which lacks the antibodies and lymphocytes that are the core elements of adaptive immune systems, nevertheless has within its blood system components that provide resistance to pathogens. One system involves the plasma protein, (2-macroglobulin, which is able to bind to microbial proteases in the blood stream. Not only does the bound (2-macroglobulin inhibit the proteases, but also blood cells recognize, remove and degrade the complexes thus formed. A second system involves a second plasma protein, limulin, which has the ability to bind to and lyse foreign cells that enter the blood stream. The two systems are functionally interrelated since protease-reacted (2-macroglobulin can enhance the lytic activity of limulin. The present studies include three objectives to define basic features of these systems. (1) The receptors on the blood cells that bind the protease-(2-macroglobulin complexes will be isolated and characterized. (2) Factors that effect the binding and pathway of uptake of the complexes by the cells will be described. (3) The molecular mechanism by which protease-(2-macroglobulin complexes and other factors regulate the lytic activity of limulin will be defined. These studies will not only allow us to understand these systems in Limulus but may also lead to predictions of similar functions for related proteins found in the b lood of more complex, higher organisms.