A tiny primitive fish that makes up 70 percent of the biomass in Tampa Bay is the “missing link” marking the point in evolution that led to the development of the modern-day human immune system.

The inch-long spineless fish, called a lancelet, produces a key immune system protein that is similar to but much hardier than the version found in people. The bay waters are a microbial soup teeming with microorganisms, yet the worm-like bottom-feeder is remarkably adept at standing up to the bacterial, viral and chemical threats in its environment. Understanding how it does so could lead to improved biodefense and better immune-boosting drugs to fight cancer and disorders such as rheumatoid arthritis, say scientists at UF and the University of South Florida, who reported their findings recently in Nature Immunology.

“At a basic level, this sea worm tells us about the evolution of the immune response; specifically, it tells us that primitive organisms have more sophisticated immune systems than we previously thought,” said X-ray crystallographer David Ostrov, an assistant professor of pathology, immunology and laboratory medicine at UF’s College of Medicine who is affiliated with the UF Shands Cancer Center. “This is the first organism below the level of jawed vertebrates that expresses the type of proteins we use in our own complex adaptive immune system.”

The human immune system is constantly at work, on guard to tackle new ills while remembering past offenders. Compared with its predecessors on the evolutionary tree, the lancelet shares genes and proteins remarkably similar to ours that enable it to also skillfully elude attack.

“This influences our therapeutic strategy because we must consider that an organism we are trying to target may have an elaborate defensive system of its own, with features that neutralize what we’re trying to do to it,” Ostrov said. “For example, if we’re trying to create a vaccine against a specific pathogen such as anthrax, smallpox or bird flu, we have to take into account the defensive measures those and other organisms might have.”

The researchers bombarded a highly concentrated, crystallized form of an immune system protein isolated from the fish with X-rays, yielding incredibly high-resolution images of its structure.

Scientists can actually see where individual hydrogen atoms are positioned in the protein’s core, providing clues as to which atoms are participating in key stabilizing interactions. The lancelet’s immune response proteins, however, are resilient. Understanding their essential architecture with such precision could lead to new, improved types of antibody-based therapies that are better able to persist in the body, Ostrov said.

The study was funded by the National Institute of General Medical Sciences, the National Institute of Allergy, Immunology and Infectious Diseases, the Cure Autism Now Foundation and the U.S. Department of Energy.

David Ostrov, ostroda@pathology.ufl.edu

Melanie Fridl Ross