Ep. 85: “Reproductive Immunology” Featuring Dr. Adrian Erlebacher
Aug 13, 2024
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Dr. Adrian Erlebacher, a Professor at UCSF, delves into reproductive immunology, focusing on immune tolerance during pregnancy. He explains how the maternal-fetal interface affects pregnancy outcomes and touches on challenges translating animal studies to human pregnancy. The importance of glycans in immune modulation is emphasized, alongside discussions about the complexity of immune responses and factors influencing preterm labor. This fascinating conversation highlights the intersection of maternal health and immunology.
Maternal-fetal tolerance is facilitated by trophoblast cells in the placenta, which interact with maternal immune cells to prevent fetal rejection.
Inflammation triggered by infections during pregnancy can disrupt normal progression and affect fetal development, highlighting complex maternal-fetal interactions.
Recent findings on nasal vaccinations reveal the importance of pre-existing B cell populations in developing effective local immune responses.
Deep dives
Understanding Maternal-Fetal Tolerance
Maternal-fetal tolerance is a paradoxical phenomenon wherein the mother's immune system does not reject the genetically distinct fetus. This concept, explored by immunologist Sir Peter Medawar, highlights how the placenta acts as a critical interface between the fetus and the maternal immune system. Research indicates that trophoblast cells in the placenta are integral to this process, as they communicate with maternal immune cells to prevent rejection. Current findings suggest that the immunological mechanisms might involve specialized glycan structures on trophoblasts that tamp down immune responses towards the fetal antigens.
Role of Immune Cells in Pregnancy Outcomes
The interaction between immune cells and the uterine environment plays a significant role in pregnancy outcomes such as preterm birth and pregnancy failure. Ongoing studies seek to understand how inflammation triggered by infections can lead to the onset of labor by activating immune responses that may disrupt typical pregnancy progression. Furthermore, researchers are investigating whether immune responses to infections can carry over into the pregnancy, potentially affecting fetal development and leading to adverse outcomes like growth restrictions. This bidirectional relationship underscores the complexity of maternal-fetal interactions in pregnancy.
New Insights into Nasal Immunization
Recent research has shed light on the origins of IgA-secreting cells in the nasal cavity, driven by the increasing interest in nasal vaccinations. The study identified the nasal associated lymphoid tissue in mice as crucial for the development and migration of IgA-producing B cells. Importantly, it was found that pre-existing populations of reactive B cells are vital for effective responses to nasal immunization. These findings could have significant implications for enhancing nasal vaccination strategies against various respiratory pathogens, emphasizing the role of localized immune responses in nasal immunity.
Impact of Microbiota on Respiratory Health
A comprehensive analysis of upper airway microbiota across different ages revealed significant shifts in bacterial composition from infancy to adulthood, suggesting that immune development correlates with microbial diversity. In infants, a higher diversity of nosocomial bacteria was noted, while adults exhibited a decrease in bacterial biomass but increased stability in diversity. The study also emphasized the influence of environmental factors, such as exposure to family members, on the nasal microbiome, in contrast to how oral microbiota shifts were more impacted by lifestyle choices like antibiotic use. Such insights are crucial for understanding how the microbiome interacts with respiratory health throughout different life stages.
Neural Control of Gut Tregs
Neuroimmunology research has highlighted the relationship between specific neurons and regulatory T cells (Tregs) in the gut, particularly involving the TRPV1 positive neurons. Activation of these neurons was shown to decrease the prevalence of Rorγt positive Tregs in the colon, possibly due to reduced proliferation rather than increased cell death. Furthermore, the interplay between neuropeptides released from these neurons and Tregs appears to shape immune responses in the gut, suggesting a local regulatory mechanism for gut immune homeostasis. These findings underscore the importance of neural signaling in modulating the immune landscape and potentially influencing gut health.
Dr. Adrian Erlebacher is a Professor in the Department of Laboratory Medicine at the University of California, San Francisco. His lab studies how the developmental properties of a tissue influence its ability to mount a successful immune response. He talks about immune tolerance in pregnancy and how the maternal–fetal interface affects pregnancy outcomes.
Immune Cells in the Skull – The glioblastoma-linked immune-cell niche in the human skull provides an unanticipated resource and concept of acute tumor reactivity in the proximal bone marrow.
Nasal Vaccine Reactions – Nasal vaccination induces B cell expansion in the subepithelial dome of nasal-associated lymphoid tissues.
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