Sequencing the Human Immune System
This spring, one of Kerafast’s providing investigators, Dr. James Crowe, Jr. of Vanderbilt University, spoke at TEDxNashville about the human immune system. His talk discussed how the body is able to defend against the constant threat of infectious pathogens and highlighted a new research project to sequence all the antibodies in the entire human population. This undertaking is the largest genetic project ever attempted.
You can view the talk, called Unraveling the Mystery of Immunity, below. We’ve also compiled our list of the key takeaways from the presentation.
- Microbial pathogens are constantly threatening the human immune system.
Infectious disease is a real and constant threat to the human population. Past examples include the black plague, which killed up to two million people per year at its height, and the 1918 influenza pandemic, which killed 50 million people in one year alone. Small pox, the first and so far only infectious disease to be eradicated by humans, caused 500 million deaths before an effective vaccine was implemented. More recently, the human population has faced a variety of threats, including the bird flu, SARS, MERS, chikungunya, Ebola and Zika.
- The human immune system is enormous, many orders of magnitude bigger than our genome.
The Human Genome Project found that our DNA only encodes for about 25,000 genes, a lower total that expected, and one that doesn’t seem to explain how our bodies can defend against so many external threats. To fight foreign pathogens, the immune system uses antibodies. Antibodies are encoded by combinations of genes, which in turn can be connected by different linkers. This provides much-needed combinational diversity. Antibodies can also mutate in response to external organisms, providing even more diversity. As a result, the human body ends up with 10 to the 18th antibody possibilities, which means you have more potential antibodies in your immune system than all the stars in the galaxy.
- A research project seeks to sequence all potential human antibodies.
A project led by Dr. Crowe, called The Human Immunome Program, is working to sequence all antibodies in the entire human population. It’s an open-source project, meaning all data will be publicly available to researchers around the world. It’s the largest genetic project ever attempted; the human immunome is estimated to be 100 billion times larger than the human genome. You can read more about the project here.
- New knowledge of antibodies is leading to treatment advances.
The goals of The Human Immunome Program go beyond simply cataloging antibodies. Dr. Crowe and his colleagues are using this information to develop new vaccines and treatments against infectious diseases. They first collect white blood cells from someone who previously fought off a disease and then pinpoint their antibodies able to inhibit and kill that virus. After sequencing those antibodies, scientists can synthesize more for therapeutic purposes.
Dr. Crowe’s team has already successfully done this for various diseases. For example, they were able to get antibodies from 100-year-old patients who survived the 1918 influenza pandemic. They also worked with a survivor of Marburg, finding antibodies in her blood able to inhibit the deadly virus. Researchers are now developing those antibodies into a treatment; for more on that project, check out a recent story published on NBCNews.com.
Dr. Crowe joined the Kerafast community in 2015 by making available his CD40L Expressing Feeder Cell Line, used to generate B cell cultures yielding human monoclonal antibodies. He has also shared via our platform human serum specimen containing polyclonal antibodies induced by natural infection with Zika virus. If you work in this area of research, check out all available reagents for studying immunology or infectious diseases.