The Reproductive Immunology Program

The Reproductive Immunology Program aims to advance the understanding of immune interactions during pregnancy under both normal and pathological conditions. By investigating how environmental stressors such as air pollution and viral infections influence maternal and fetal immune responses, this program seeks to elucidate mechanisms of fetal immune development and identify potential interventions to improve maternal and fetal health outcomes.

Research Program

A Bold New Approach:
Strengthening The Immune System In Our Children

The Reproductive Immunology Program at the C.S. Mott Center will contribute to a comprehensive understanding of the immune mechanisms governing pregnancy and fetal immune system development, ultimately leading to improved maternal and child health through these objectives:

Maternal-Fetal Immunology

The interactions between maternal and fetal immune systems are crucial for a successful pregnancy, balancing immune tolerance and defense. At the maternal-fetal interface, primarily the placenta, immune cells from both mother and fetus engage in complex interactions to prevent maternal immune rejection of the fetus and protect against infections. Key mechanisms include the regulatory roles of T cells, the expression of immune checkpoint molecules, and the unique cytokine environment. Understanding these interactions is crucial for addressing pregnancy complications like preeclampsia and recurrent pregnancy loss, and it opens avenues for developing targeted therapies to improve maternal and fetal health outcomes.

Environmental and Infectious Exposures

Environmental and infectious exposures significantly impact placental function and fetal immune system development. Investigating specific pollutants like benzene reveals how toxic substances can alter placental responses, potentially leading to impaired nutrient and oxygen exchange, and contributing to adverse pregnancy outcomes such as preterm birth and low birth weight. Similarly, pathogens like the Zika virus can infect the placenta, triggering immune responses that may disrupt its function and compromise fetal development. Understanding these effects helps in identifying critical windows of vulnerability during pregnancy and underscores the importance of minimizing exposure to harmful pollutants and pathogens to safeguard maternal and fetal health.

Immune Regulation in Pregnancy Disorders

Exploring the immunological basis of common pregnancy complications such as preeclampsia and preterm birth is crucial for developing preventive and therapeutic strategies. Preeclampsia, characterized by high blood pressure and damage to organs like the liver and kidneys, affects about 5-8% of pregnancies and can lead to severe maternal and fetal morbidity and mortality. Preterm birth, occurring before 37 weeks of gestation, is the leading cause of neonatal death and long-term health problems. Both disorders often arise from dysregulated immune responses at the maternal-fetal interface, leading to inflammation, impaired placental function, and adverse pregnancy outcomes. By investigating the underlying immune mechanisms, such as the roles of specific immune cells, cytokines, and signaling pathways, researchers aim to identify biomarkers for early detection and targets for intervention. This research holds promise for improving maternal and fetal health by enabling timely and effective management of these pregnancy complications.

Maternal Immunoglobulin Transfer: Ensuring Early Immunity

Maternal immunoglobulin transfer during pregnancy plays a critical role in providing passive immunity to the developing fetus, significantly impacting neonatal health outcomes. Immunoglobulins including IgG and IgD transferred from the mother to the fetus not only protects newborns against a broad spectrum of infectious diseases but also influences the development of the infant’s immune system. Recent studies have shown that maternal immunoglobulins can modulate immune responses in the newborn, potentially reducing the risk of developing asthma and allergies. By binding to allergens and antigens, maternal antibodies can prevent the sensitization of the neonatal immune system to these substances, thus lowering the likelihood of allergic reactions and asthma later in life. Furthermore, maternal immunoglobulins may also promote the maturation of the infant’s regulatory T cells, which are crucial for maintaining immune tolerance and preventing hypersensitivity responses. Therefore, the transfer of maternal antibodies is not only vital for immediate protection against infections but also for shaping a more resilient and balanced immune system in the offspring.

Longitudinal Studies

Conducting longitudinal cohort studies to track immune changes from preconception through postpartum is essential for understanding the dynamic nature of immune responses during pregnancy and their impact on outcomes. These studies involve detailed monitoring of specific immune parameters, such as cytokine levels, immune cell populations, and antibody profiles, at multiple time points. By correlating these immune changes with pregnancy outcomes, such as gestational age, birth weight, and the incidence of complications like preeclampsia and preterm birth, researchers can identify specific biomarkers and immune patterns that predict adverse events. Furthermore, tracking maternal immune status during pregnancy and assessing child health outcomes, including immune system development and susceptibility to infections or autoimmune conditions, can provide valuable insights into the long-term effects of maternal immune activation. This comprehensive approach helps in identifying critical periods for intervention and guiding the development of targeted strategies to improve maternal and child health across the lifespan.