Ep. 30: “Comparative Immunology and Sharks” Featuring Dr. Hanover Matz
Jun 7, 2022
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Dr. Hanover Matz, a Postdoctoral Fellow at the University of Maryland specializing in comparative immunology, dives into the fascinating immune systems of sharks. He explains how sharks have evolved unique adaptive immune responses and the role of T cells and antibodies. Matz also discusses the innovative work at aquaculture centers, where they immunize nurse sharks, revealing the potential medical applications of shark-derived antibodies. The conversation highlights the surprising complexities of shark immunity compared to mammals, offering intriguing insights into future research.
Sharks possess a distinct adaptive immune system characterized by the specialized antibody isotype IgNAR and unique B-cell organization.
The robust innate immune system in sharks serves as the primary defense, while their adaptive immunity is slower and aims at long-term protection.
Research into shark T cell populations identifies key subsets that resemble those in mammals, highlighting their significance in immune defense mechanisms.
Deep dives
Comparative Immunology in Sharks
The episode covers the research of B-cell repertoire and affinity maturation in sharks, highlighting their unique immune systems that include adaptations not found in other vertebrates. Sharks possess a specialized antibody isotype called IgNAR that aids in their immune response against pathogens. This study of cartilaginous fish, which include sharks and rays, reveals how their immune systems function differently from those of mammals, particularly in terms of B-cell organization and the absence of germinal centers. The research suggests that the understanding of shark immunity can provide insights into the evolution of adaptive immunity and potential applications in biotechnology and medicine.
Innate and Adaptive Immune Responses
Sharks exhibit a robust innate immune system that includes many similarities to mammals, such as complement systems and various innate immune cells. However, the adaptive immune response in sharks is notably slower, taking significantly longer to produce protective antibody titers compared to mammals. The episode emphasizes the role of innate immunity as a primary defense mechanism, indicating that the adaptive immune system plays a secondary role, mainly for long-term protection in chronic infections. This understanding highlights the evolutionary pressures that shaped the immune systems of both sharks and mammals, suggesting that size and longevity may influence immune complexity.
The Role of T Cells in Shark Immunology
The discussion includes the presence of T cells in sharks, which were historically poorly understood, but recent research suggests the existence of several T cell subsets akin to those in mammals. Notably, this research shows that sharks have CD8 T cells and potentially CD4-like T follicular helper cells, although the latter remains less defined. Gamma-delta T cells are also prevalent, believed to play critical roles, yet their specific functions remain largely unidentified. This investigation into T-cell populations sheds light on the basic mechanisms of immune defense in sharks, contributing to the broader understanding of vertebrate immunology.
Mechanisms of Somatic Hypermutation
The episode delves into how sharks achieve affinity maturation despite lacking germinal centers, indicating that they possess mechanisms for somatic hypermutation. This finding suggests that selective pressures in their evolutionary history may have favored a slower but efficient immune response that allows for receptor diversification. The researchers propose that this unique approach enables sharks to maintain a diverse antibody repertoire critical for responding to various pathogens. The idea that sharks can undergo somatic hypermutation opens up exciting research avenues regarding their immune defense strategies and potential applications for therapeutic antibody development.
Potential Therapeutic Applications
The discussion highlights the potential biomedical applications of shark antibodies, particularly the IgNAR isotype, which can be used as innovative tools in diagnostics and therapeutics due to their high specificity and binding affinity. These antibodies hold promise for developing treatments against diseases, including cancer, by targeting specific biomarkers that may be difficult to detect using traditional mammalian antibodies. Furthermore, because shark-derived antibodies can recognize targets that are challenging to obtain immune responses against in mammals, they present opportunities for groundbreaking research in immunotherapy. The continued exploration of shark immunology may lead to novel therapeutic avenues and enhance the understanding of vertebrate immune systems.
Dr. Hanover Matz is a Postdoctoral Fellow at the University of Maryland, who recently completed his PhD under the supervision of Dr. Helen Dooley. He discusses why sharks may have evolved adaptive immune systems, the role of T cells, mucosal immunity, and antibodies, and working with sharks in the lab.
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