Irina Grigorova, PhD
Current Research Activity:
Humoral (Antibody) Immune Response Initiation Dynamics
The mammalian immune system has evolved to respond to a variety of infectious agents by integrating “danger signals” into distinct signaling outcomes and thus distinct dynamics of intercellular interactions. When the immune response is successful, disease eradication occurs. Our research interests are directed at understanding the quantitative principles that underlie this "signal processing" in an adaptive immune response, specifically in initiation of the humoral (antibody) immune response.
The humoral immune response is crucial for resistance against viral and bacterial infections. Antibodies are protein molecules that bind to infection-specific, foreign molecular determinants, called antigens (Ag). Upon infection, antigen drains into secondary lymphoid organs that are filled with T and B cells that recirculate through the lymph and blood circulatory system. In lymph nodes (LNs), foreign antigens activate a very small number of B and helper T cells specific for the particular Ag. For a T-dependent humoral response to start, these extremely rare B and helper T cells that migrate in the LNs have to find each other among ~ 106 -107 other lymphocytes in order to form a specific interaction. During these specific interactions activated by antigen B cells get appropriate signals (help) from the respective T cells that enable B cells to proliferate and differentiate into plasma cells (that secrete antibodies) or germinal center cells. Even though activated T cells are proliferating and activated helper T and B cells move to the interface between their resident T and B zones in the LN, it is still unclear whether the timing of the early B cell response could be entirely explained by their random encounters. In my lab we are using a combination of approaches to study the interactions between activated Ag-specific B and T cells. We use two-photon intravital microscopy (that enables imaging cell migration and interactions in the LNs of living mice) in combination with standard immunological techniques, including flow cytometry and ELISA, to measure the extent of responses on a single cell and organismal level, respectively. Quantitative data obtained by two-photon imaging are then used to build mathematical models of activated T and B cell migration and interaction in lymphoid organs. By combining the experimental and modeling approaches, we will explore whether there are any currently unknown factors that could promote/facilitate the interactions between rare activated T and B cells.
Recent Selected Publications
Grigorova I, Panteleev M, Cyster JG. Lymph node cortical sinus organization and relationship to lymphocyte egress dynamics and antigen exposure. PNAS 107(47): 20447-52, 2010 Nov 23.