The Fetus Fights Back
Not so defenseless: The human fetus can develop its own immune response in utero, says Dr. Claire Chougnet.
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Animal models, particularly mouse models, cannot replicate the development of the human immune system, says Claire Chougnet, PhD. The best method available for studying human immunity in its earliest stages is cord blood taken just after delivery, but that presents its own set of problems. It can be contaminated by the mother’s cells, or altered by the physiological stresses of delivery. The function of the immune cells found in that circulating blood is not always identical to that of immune cells found in tissue.
Nevertheless, research has shown that the human neonate is able to mount an immune response of its own, says Chougnet, a scientist in the Division of Molecular Immunology at Cincinnati Children’s who has spent her career studying the intricacies of the immune system.
Signs of Early Independence
“We know that the adaptive immune system in humans can be primed to respond, even as early as in gestation,” Chougnet says. “The type of response that a neonate will mount is not the same as an adult’s, but there is the capacity for response.”
This is a significant change from earlier thinking that the fetus’s immune system was basically unformed.
“A number of years ago, you would read broad statements about the immunology of the neonate saying that T-cells are not very functional in the neonate,” says Chougnet. “But now we have come to look at the many different subsets of T-cells, and we are seeing that some of the responses are at least at the same level as an adult response.”
Chougnet’s focus has been on HIV infection in children and adults, and in infants born to HIV-infected mothers.
“In a sizeable proportion of babies born from an HIV-infected mother, we can detect T-cells that respond to HIV antigens when they’re born, or shortly after they’re born, even if they’re not infected themselves. Similarly, infants congenitally infected by cytomegalovirus (CMV) exhibit CMV-specific T-cell responses at birth. This means their immune systems have been primed to respond to the antigen while they were in utero. So we know that in some ways, the T-cells are able to respond.”
Not Unlike Adult Response
When asked why one fetus would respond to infection in utero by prematurely exiting the womb while another would not, Chougnet explains it is likely the same as why two adults differ in their reactions to infection. She attributes it to a complicated blend of genetic differences, timing and the strength of the infection. An additional level of complexity is the human leukocyte antigen (HLA) disparity between mother and fetus, which likely participates in the shaping of the immune responses mounted by the fetus.
In the end, Chougnet explains, the immune system is all about balance and control, even in early fetal development.
“The immune system is fine-tuned, and almost all of its responses are extremely controlled. In any type of response, there is an activation phase and a shutdown phase. If an individual does not have a developed activation phase, the infection might not be controlled sufficiently. And without a good shut-down response, the individual will have uncontrolled inflammation or activation of effector cells that start to attack tissue.”
