BioEd Online

When discussing the attributes that make mammals special, a sophisticated immune response generally comes close to the top of the list. But now it seems that we’re not so unique after all.

Researchers have found that fish-like creatures called lampreys have evolved their own system, using building blocks that are completely unrelated to the antibodies found in mammals. The discovery opens up a new world for immunologists, who had previously assumed there was only one way of doing things – ours.

“The result blew my mind,” says Chris Amemiya, molecular geneticist at the Benaroya Research Institute in Seattle, and an author of the study. “Now we know there are at least two ways of making the adaptive immune system."

Shifting sequences

There are two types of immune response, innate and adaptive. Both spot and destroy pathogens such as viruses, bacteria and fungi. Innate immunity is inherited, and does not change over an animal’s lifetime.

In contrast the adaptive system changes according to the antigens an animal encounters. Specialized genetic sequences shuffle together to generate an almost infinite variety of defence cells, which attack antigens using proteins called antibodies.

A particular antigen triggers the genetic sequence that recognises it to begin copying itself, producing antibodies to fight that antigen.

Scientists believe that the adaptive immune system evolved at around the same time as animals developed jaws, about 400 million years ago. They hoped to find signs of a primitive system in the lamprey. It doesn’t have a jaw, but it does show some of the characteristics of an adaptive immune system, such as rejecting skin grafts.

But there was no hint that lampreys made antibodies.

Amemiya’s group wondered whether the lamprey might be attacking foreign molecules in some other way. To test the idea, the team injected lamprey larvae with a cocktail of antigen molecules, then compared the genetic sequences of the inoculated animals with untouched ones.

They found that animals exposed to the pathogens produced 13 times more copies of a genetic sequence that generates a pathogen-binding protein that is unrelated to an antibody. "The lamprey has gone for a different basic building block to construct mechanisms to recognize antigens," says Hugh Reyburn, an immunologist at the University of Cambridge, UK.