When a host (person or animal) is exposed to a substance that causes an immune response, under certain circumstances the body generates antibodies. Although the generation of protective antibodies is the purpose of vaccinations, there is very little understood about the role of chemokines in controlling the numbers and types of antibodies that are produced during the secondary immune response. C-C chemokine receptor 7 is a chemokine receptor that regulates the levels of antibodies made. The goal of our studies is to learn how a host uses C-C chemokine receptor 7 to regulate the levels of antibodies that are made during a secondary immune response. This is important since antibodies provide protection to the host when he/she is exposed to the same substance during a secondary immune response. We hypothesize that loss of CCR7 or signaling to downstream effectors such as ERK5 will disrupt targeting of effector memory T cells leading to increased antibody production following the second exposure to an antigen. With the knowledge we gain we will determine if promoting CCR7 signaling during vaccination against a specific self-antigen, and in the near future, can be used to prevent excessive production of antibodies observed during autoimmune disease.
Vaccination is arguably the most effective medical tool developed from scientific discoveries that can be used to protect both humans and animals from diseases. The proposed studies are designed to improve our knowledge of the cellular and molecular mechanisms that are controlled by C-C chemokine receptor 7 (CCR7), that regulate titers of high-affinity IgG antibodies that protect the host (person or animal) from disease or are elevated during certain autoimmune diseases. Thus, completion of these studies may provide knowledge that can be used to increase antibody production during vaccination or decrease exacerbated immune responses during autoimmune disease.
