MCA Pilot PUI: Genomic Diversity, Adaptive Immunity and Immune Memory

Cuny Brooklyn College, Brooklyn NY

Investigators

Abstract

How do animals protect themselves from disease? The majority of vertebrates have an adaptive immune system that retains a record of past infections, allowing for a more robust immune response upon reinfection. The recent discovery of animals that are capable of surviving infection despite the loss of key components of this adaptive immune system offers an opportunity to better understand the structure and function of the immune response in animals. This research uses a unique evolutionary experiment to directly compare immune function and memory in a species with an intact adaptive immune system with one that has lost major components of its adaptive immune machinery. This Mid-Career Advancement award will enhance national research capacity in comparative immunology through a research collaboration between the City University of New York and the University of Maryland Medical School, and will offer unique educational and training opportunities to undergraduate and graduate students interested in understanding adaptive immune function. Such findings can ultimately identify resilience in animals. The presentation of pathogen-derived antigens by Major Histocompatibility Class II molecules (MHC II) on the surface of antigen-presenting B-cells, dendritic cells, and macrophages is thought to be essential for eliciting both an immediate antibody response and for activating memory B- and T-cells that preserve a record of past infection. Members of the Family Syngnathidae (seahorses and pipefish) have independently lost key components of the MHC II pathway, and would therefore be expected to lack immune memory, a hallmark of the adaptive immune response. This research project aims to capitalize on this unique evolutionary model to address test three major questions related to immune system structure, function and memory. A first experiment will use single-cell RNA sequencing to characterize immune activation following primary immunization of experimental animals with heat-killed bacterial pathogen. A second experiment will employ two rounds of immunization to test the memory response in species with- and without an intact MHC II pathway. A final experiment will test immune function by following primary immunization with secondary exposure to live bacteria. Experimental immunization is expected to be ineffective in animals lacking the MHC II axis, and fail to provide protection against secondary exposure. The explicitly comparative nature of this research, comparing immune system structure, function and memory in species with- and without a fully intact adaptive immune system, offers an especially powerful test of central questions in adaptive immunity and an opportunity to learn more about the evolutionary diversity of the immune response. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.