When you think about your own health and immune system, sharks probably never cross your mind. However, sharks and humans may have more in common than you think, despite having last shared a common ancestor 450 million years ago. Dr. Helen Dooley, Associate Professor of Microbiology and Immunology at the University of Maryland School of Medicine, has spent over 20 years uncovering just how similar shark and human immune systems are.
Shark Immune System
“When I started working in this field, we knew shark immune components were similar to humans, including B cells, T cells, and MHC; however, immunization studies suggested shark immune responses were primitive and poorly protective. The work of our group and others has shown that while the shark immune system is ancient, it is far from primitive. It is almost as sophisticated as the human immune system, meaning far fewer major changes have happened over the last 450 million years than was initially thought,” said Dr. Dooley.
One key difference, however, is that sharks do not have lymph nodes, leaving researchers wondering how sharks conduct system-wide immune surveillance.
Shark Pancreas has Immune Tissue
An exciting discovery led by Thomas Hill, Ph.D. candidate in the Dooley Lab, may have uncovered part of the answer. The findings, published in The Journal of Immunology, reveal that nurse shark pancreas contains organized immune tissue in the form of B cell follicles. These follicles are spatially distinct from the exocrine and endocrine tissues of the pancreas and exhibit many of the hallmarks of B cell selection previously known to occur in the nurse shark spleen. Based on these functional characteristics it appears the nurse shark pancreas may function as a secondary lymphoid organ.
“This discovery came as a surprise,” said Hill. “I was looking at shark tissues under the microscope out of curiosity and while I had read that shark pancreas might have immune function, I had never looked at it before. By chance, I looked at a tissue section and saw these large, impressive, clusters of cells that, to me, looked exactly like the B cell follicles found in shark spleen.”
“When Thomas brought me this, my first reaction was that we must have mislabeled the tissue samples or something else had gone wrong; the findings were so surprising,” added Dr. Dooley. Seeing B cell follicles in human pancreas would be indicative of a disease state like cancer or diabetes. “While there were reports of immune gene expression in the pancreas of sharks and maybe some other animals, like bony fishes, organized immune tissue had never been described. Interestingly in some reptiles, the spleen and pancreas form a combined organ called a splenopancreas, indicating the pancreas may have some ancient association with immune tissue,” said Hill.
Deeper Understanding
For both Dr. Dooley and Hill, this newfound role for shark pancreas broadens the understanding of the shark immune system. “This highlights the fact that other organs, like the pancreas, may be incorporated into the shark immune system as a means to conduct immune surveillance in the absence of lymph nodes,” said Hill.
Understanding immune systems that came before humans can tell us a lot about human health. Dr. Dooley compares only studying mammalian immune systems to only reading the final Harry Potter book or only watching the final episode of Game of Thrones. While you know the ending, you have no idea how each character (or immune component) got to that point. “While the human pancreas no longer has significant immune function, that it served this role in the past may explain why it is susceptible to inflammation and immune cell infiltration during disease,” said Dr. Dooley.
“Studying sharks, and comparative immunology in general, is so important because sometimes we find things we could never have imagined that better inform us about human conditions and diseases or we may discover new tools, like shark nanobodies, that can be harnessed to cure human disease,” said Dr. Dooley.
This paper can be found in The Journal of Immunology (The JI), published by the American Association of Immunologists. As one of the most highly cited journals in the field of immunology, The JI is committed to describing novel findings in all areas of experimental immunology, including basic and clinical studies.
