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.
