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RESEARCH

Research is focused on comparative immunology, specifically the immune response of bony fish (teleosts) to the common protozoan parasite Ichthyophthirius multifiliis. This virulent ciliate (see life cycle) is well known in commercial aquaculutrure as the etiological agent of "white spot," a disease that afflicts a wide range of freshwater fishes. While Ichthyophthirius is highly pathogenic, animals exposed to controlled infections develop a strong acquired resistance to the parasite.

Our studies suggest that host resistance involves a novel mechanism of humoral immunity affecting parasite behavior. Rather than being killed, parasites are forced to exit the fish prematurely in response to antibody binding. The target antigens involved in this response are a class of highly abundant glycosylphosphatidly-inositol-anchored coat proteins referred to as immobilization antigens(i-antigens). We study this immune response to learn more about the basic mechanisms of immunity in lower vertebrates as well as to develop vaccines for use in aquaculture.

In addition to directly killing parasites (through immobilization) or blocking their attachment within the host, it has been argued that antibodies may have subtle effects on parasite behavior, leading to host resistance. This idea is intuitively appealing given that parasites express a variety of surface receptors that could potentially interact with immunoglobins. Such interactions might interfere with any number of signal transduction pathways, resulting in profound effects on parasite physiology. Nevertheless, surprisingly few examples of antibody-mediated effects on parasite behavior exist. In part, this may reflect an inherent ability of parasites to sequester receptors (and other surface antigens) as a means of surviving within the host. At the same time, assaying for physiological effects of antibodies in vivo is difficult at best. Ichthyophthirius offers some advantages in this regard. Because it is confined to the epidermal layers of the skin and gills, it can be visualized by light microscopy from the time it invades the fish until the time it exits. Consequently it provides a unique system for the study of host-parasite behavior and suggests a mechanism of humoral immunity not previously characterized.

Ichthyophthirius and channel catfish (the laboratory animal used in our studies) also provide a good host-parasite experimental system for research on the mechanisms of mucosal immunity. With existing reagents (mousemAbs against parasite i-antigens and catfish immunoglobulin), it is possible to design in vivo and in vitro experiments to elucidate the basic components and kinetics of the teleost cutaneous mucosal immune response. In mammals, the production of enteric mucosal antibody is initiated locally either by direct antigen stimulation of resident lymphoid cells or through migration to mucosal surfaces of antigen-specific lymphocytes generated in the gut-associated lymphoid tissues. Some evidence exists for such a mechanism in fish as well. By analogy, we hypothesize that the skin of the fish is also an active participant in the immune response, serving as both an inductive and an effector site, and not merely as an end target tissue of antibody deposition. Thus, methods used to evaluate the trafficking of mammalian cells among mucosal surfaces and their appropriate systemic immune organs should be applicable to similar studies in channel catfish. For instance, using ELISPOT assays with mAbs specific to i-antigens and to catfish immunoglobulin, we are working to isolate and quantitate i-antigen specific antibody-secreting lymphocytes in the skin and primary lymphoid tissues of the fish following parasite challenge.