In the fast paced world of immunological research, it’s not your p’s and q’s you have to mind, but your b’s and t’s. That’s B cells and T cells, two of the main players in the complex orchestra that makes up your immune system. B. Paige Lawrence, assistant professor in the College of Pharmacy, keeps track of both in her research into how the environmental contaminant dioxin affects immune system function but spends most of her time with T cells.
Dioxins are the byproducts of many industrial processes, including the incineration of municipal and medical wastes and of plastics. While they are destroyed by heat, dioxins reform as smoke cools in the incinerator smokestacks.
There are many different dioxins, and Lawrence studies the most toxic of them, TCDD, or 2,3,7,8,-tetrachlorodibenzo-p-dioxin. TCDD is ubiquitous, found in the water, on soil, on plants. Because it is not metabolized by the body but stored in body fat, the higher up in the food chain that you eat, the more dioxin you’ll accumulate. Especially if your diet includes meat.
Lawrence uses the mouse to study the effects of dioxin on the immune system. “You have to ask the immune system to do something if you want to study it,” she says. Since influenza is a common human ailment, we know a lot about how the human system responds to it. And we know that the mouse’s response to flu is quite similar to ours.
Normally, a flu virus invasion of the lungs is detected by several different immune system cells. Some are part of the non-specific immune response and will fight anything they encounter that’s not “you.” Others are specific for a part of the flu virus and will respond to and fight only it.
When cells specific to the flu virus encounter it, they travel to lymph nodes near the lungs and activate T cells that also are specific to that virus. The activated T cells then reproduce. If they are “cytotoxic” T cells, their offspring will travel to the lung to kill the cells infected with flu virus. If they are “helper” T cells, their offspring will secrete chemicals that help the cytotoxic T cells and any other immune cells that might get involved in the fight. Helper T cells are the conductors of the immune system orchestra, and without them, all the rest don’t know what to do, says Lawrence.
When mice have been exposed to dioxin, neither type of T cell does its job. “It’s not that they’re dying, but for some reason they’re just sitting there doing nothing,” says Lawrence.
Lawrence’s lab is working on several projects aimed at determining how dioxin causes this effect. At this time, they know that dioxin attaches to a specific protein that’s found on the inside of all cells in the body that have been surveyed. That attachment ultimately results in a change in the normal function of those cells , mostly by changing what proteins the cell makes. The cellular functions affected by dioxin seem to vary from cell to cell, says Lawrence, and it’s not known exactly what is affected in T cells. In fact, it’s not yet known for certain that dioxin even attaches directly to a protein within T cells.
Another project is assessing whether prenatal or postnatal exposure to chemicals has an effect on an offspring’s immune function. The lab’s first experiment designed to address this question gave dioxin to pregnant mice at levels that are immunosuppressive in adult animals. Although live mouse pups were born, most of them died within 24 hours. A fortuitous switch at birth of some to a mother mouse that hadn’t been treated with dioxin produced pups that did survive beyond 24 hours. Lawrence suspected that the reason for the death of most of the pups was that the mother’s exposure to dioxin inhibited or impaired mammary gland development. A subsequent experiment supported that conclusion.
An additional experiment used lower doses given during fetal development and after birth via breast feeding. It suggested that exposure to dioxin during fetal development causes defects in the immune function of female but not male offspring. These results are preliminary and will be verified using other pathogens. The lab also plans to test whether exposure to dioxin after, but not before, birth has any effect on immune function, for dioxins and other fat-soluble chemicals have been found in human breast milk.
Lawrence’s work is typical of much current research into the effects of environmental chemicals, an example of a paradigm shift that’s taken place over the last few years. Early research focused on whether environmental chemicals caused cancer and usually considered high dosage levels. Now many researchers are concerned with much lower exposure levels and concentrate on whether there are effects on development or on any one of a number of body systems such as the immune, reproductive, or neurological systems.