World Aquaculture 49 immunization, which allows vertebrate animals to be specifically vaccinated against particular diseases. The ability of antibody-based immune systems to remember previous infections allows vertebrates to be vaccinated against selected diseases. For instance, humans can be vaccinated against pandemic diseases, such as, polio or smallpox. Attenuated (harmless) versions of the disease causing agents are injected into an individual to trick the immune system into mounting an antibody response that is fine-tuned for that particular disease. This generates disease-specific memory cells targeted specifically against the microbe used in the vaccination. Sometimes the memory response generated by vaccination is so effective that it lasts the remainder of the individual’s life. When a real, virulent infection by the same disease agent happens, the immune system is already primed to mount rapid, disease specific responses to that particular pathogen. Exactly the same process allows fish to be vaccinated against many of the major bacterial diseases that affect aquaculture production, including various species Vibrio, Edswardsiella, Flavobacteria and Aeromonas. These vaccines can provide long-term protection from disease, without which many fish aquaculture industries could not remain commercially viable. Can Invertebrates Mount Disease Specific Immune Reactions? From everything presented so far, it is clear that there are two requirements for an animal to be able to mount disease-specific immune responses… • The ability to produce hypervariable defense molecules that can differentiate between different disease-causing organisms with great accuracy and, • Ways of linking those molecules to killing mechanisms, so that disease-specific immune response can be generated. For years after the discovery of antibody-based adaptive immunity in vertebrates, it was thought that invertebrates lacked both of these essential criteria for disease-specific immunity (Raftos and Raison 1992). In hindsight, the failure Fig. 6. The generation of molecular “hypervariability” in sea urchins. Fig. 7. The design of classical vaccinations experiments. to detect hypervariable defense molecules and pathogen-specific immunity among invertebrates may end up saying more about our failure to look in the right places than it does about the absence of such systems. Most research in the past has been biased by our own view of what these systems should look like. That view was usually anthropocentric. In many instances, we believed that all disease-specific immune systems should mirror our own. That view now seems flawed. New technologies are revealing the existence of hypervariable gene systems among a number of different invertebrates that may be involved in anti-pathogen defense. None of those systems produce molecules that look like antibodies. So far, hypervariable genes that are associated with defense have been identified in sea urchins, snails, lancelets, sea squirts and flies. For the remainder of this article, we focus on the hypervariable molecules from sea urchins because one of us, Sham Nair, working with Courtney Smith in Washington DC, was responsible for their discovery and both of us are still closely involved in work on this new system. The hypervariable genes from sea urchins have been designated 185/333s, or 185s for short. This name is based on the original gene lodged in the Genbank gene sequence database during the early 1990s. Even though a single version of these genes had been known for almost 10 years, it wasn’t until Sham Nair and Courtney Smith started to characterize the immune response of sea urchins at a genetic level that the true significance of 185 genes became apparent. When sea urchins were vaccinated with bacteria, or bacterial molecules, more than 60 percent of all the sea urchin genes activated turned out to be closely related to the original 185/333 sequence from Genbank. That was unusual. Most often, hundreds if not thousands of different genes are turned on during an immune response. One particular set of genes usually doesn’t predominate as 185s seemed to do in sea urchins. On closer inspection, it became obvious that 185 genes coded for a large family of hypervariable defense proteins. We don’t yet know exactly how many subtly different 185 proteins can be made by an individual sea urchin. But we do know that the number is greater than 100, and probably much higher. So far, more than 800 different 185 gene sequences have been identified within populations of sea urchins. The 185 genes seem to be constructed by a combination of two different processes. When the DNA sequences of different 185 genes are aligned with one another, it becomes obvious that the sequences can be divided up into about 27 different blocks, or elements of DNA. Those elements, and the way (Continued on page 67)
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