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Immunologist Martha Zúñiga studies the ways our bodies fight illness.
Last time you were sick, what were your symptoms? How did you get better?
If someone tells you that you have a major histocompatibility complex, you might reply with an insult or worry that they’re calling you crazy. But that person has one, too. The major histocompatibility complex (MHC) is part of the immune system, which helps keep us healthy by protecting us from viruses, bacteria, chemicals, and natural allergens that can make us sick. Immunologist Martha Zúñiga studies MHC molecules, using transgenic mice to explore how they work. (What are transgenic mice? Read on to find out.)
“I’m a child of Sputnik,” Zúñiga told Math4Science. “I was born in 1950 and I benefited from two things: [first] the fact that the United States was terrified that the Russians were going to beat us (so they started to pour a lot of money into science) and second, Lyndon Johnson was President.”
Martha grew up in Laredo, Texas. Her home town, located on the U.S.-Mexican border, was considered one of the poorest cities. President Johnson “was a Texan, so Laredo was on his radar screen and had a lot of money pouring into it for science education.” “My natural bent for science,” evident when Martha examined animals her father brought home after hunting and when she read Scientific American magazine, “was given a lot of opportunity to flower.”
When a group of scientists from NASA visited Martha’s school, one of them told students that things they were doing might impress them “but when you grow up you will do things that make what we are doing look very pedestrian.”
According to Zúñiga, “I felt he was talking right to me: he was telling me that I could become a scientist.” So when her high school biology teacher urged her to apply to a summer program sponsored by the National Science Foundation (NSF), she applied and ended up in New Orleans, at Loyola University.
“In the Laredo school system, we had a single [guidance] counselor. I hate to say it, but he was looking out for the boys” and steered Zúñiga away from work as a scientist. “I was smart and I could go out and major in education,” he said, “and I could come back and teach in the Laredo public school system. But these people in this [NSF summer] program said “No, no, no: we are helping you — you are a budding scientist or a budding mathematician.”
Zúñiga went on to study zoology in college and received a PhD in biology at Yale University.
When you get the flu, dendritic cells break up the cells of the virus that is making you sick. They carry the pieces of the virus to areas where you have many T-cells and B-cells. T-cells and B-cells each recognize parts of viruses, such as the one causing your flu. When they detect that virus or another antigen on dendritic cells, they multiply, creating a tiny army to fight the antigen and help make you healthy again. “When a T-cell sees a virus antigen, it doesn’t see it all by itself but rather it sees it in the context of the major histocompatibility complex (MHC).”
Zúñiga explains that “every day of your life, you’re producing new T-cells and B-cells.” Some of them are helpful but some can attack the body’s tissue. “These cells are screened for whether they’re useful for getting rid of something foreign. You have to get rid of [T- and B-] cells that would potentially attack your own tissues.”
How does your body find and kill the T-cells and B-cells that might cause you to reject useful tissue? How does it decide which T-cells and B-cells to keep — the ones that will help you fight antigens, getting rid of molecules that can hurt you? These are the questions Zúñiga and her team explore.
There are times when people need new organs, for instance a liver or kidney transplant or even a new heart. Burn victims and people wounded in other ways might need some of their skin replaced. One problem doctors face when putting new tissue into someone’s body is that when the immune system detects it, it may assume that the new cells are antigens. When this happens, the person’s body rejects the transplant.
In order to understand what causes a body to reject some transplants and accept others, Zúñiga uses transgenic mouse technology. “You can create a mouse that is expressing a gene that you want to study.” An infertile male mouse puts a female mouse into a “pseudopregnancy,” making her body ready to accept fertilized eggs from two other (fertile) mice. Those eggs are injected with the gene Zúñiga and her colleagues wish to study. “We modify the gene so that we can make sure that it’s only expressed in certain tissue, not in all of the tissue.”
“Now you implant those fertilized eggs into the pseudopregnant female. She will give birth to pups and some of them will have the gene in them and you can generate a line of mice that differ from what they would have been, because now they’re expressing the gene you put into them.” Voila: transgenic mice.
Using these mice and other sophisticated technology, including a hemocytometer and fluorophores (fluorescent molecules which attach to antibodies, marking them with different colors), Zúñiga and her team are extending our understanding of how the MHC works, hoping to make transplants safer and more likely to be accepted by the immune systems of the people receiving them.
The results of Zúñiga’s research help us better understand our immune systems and may lead to more effective transplant surgeries. No doubt they would also impress the NASA scientist who predicted she would do great work.
