Researchers at Seattle BioMed aim to study the host response to diseases of global importance. Understanding how a human or animal host deals with the invading virus, bacterium, or parasite involves studying the immune cells and how they respond to the infection. Importantly, each of these pathogens utilizes different ‘tricks’ to evade the immune system and cause disease. Some infections, such as HIV and Tb, even live inside cells of the host’s immune system. To effectively understand the host side of the equation immunologists need to work in close collaboration with virologists, bacteriologists and parasitologists, and Seattle BioMed is a place where this can happen. To achieve this, Faculty focusing on immunology are now an integral part of the disease-focused programs of Seattle BioMed. These efforts are designed to increase the effective development of vaccines, diagnostics and drugs through a more complete understanding of the complex cross-talk between host and pathogen.

The immune system comprises defensive cells that are distributed around the body in the blood and in tissues, and cells that are concentrated in specific organs such as the lymph nodes and the spleen. Any parasite that enters the body must confront antibody, which binds to the invader and may prevent it from entering susceptible tissues, or targets it for destruction in immune cells such as granulocytes and macrophages. Dr. Leonidas Stamatatos is pursuing research to identify kinds of antibody that most effectively neutralize HIV, and ways to promote such antibodies through vaccination. Many bacteria, many parasites and all viruses grow inside cells of the host, and once inside cells they are largely protected from antibody. To pathogens inside cells, the immune system responds with T cells. Thus, Dr. Ruobing Wang is using experimental models to identify new biomarkers of protection against sporozoite-based malaria vaccines, and leads the Malaria Clinical Trials Center immunology laboratory, which is dedicated to vaccine discovery and the measurement of the T cell response in human volunteers in Seattle. In parallel, Dr. Michal Fried evaluates immune responses in malaria patients in Tanzania. In HIV infection, T cells of the CD4+ subset are targets of the infection, while CD8+ T cells make a response. To determine which kinds of immune response are linked to long survival, Dr. Helen Horton measures CD8+ T cell responses to HIV in patients’ blood samples obtained as part of a collaboration with the Fred Hutchinson Cancer Research Center.

Experimental malaria vaccines are created in the laboratory of Dr. Stefan Kappe, while his colleague Dr. Sebastian Mikolajczak investigates the contribution of innate immune cells to anti-malaria immunity. The malaria parasite must undergo part of its maturation inside liver cells, and the nature of the T cell responses to such parasites is investigated in the laboratory of Dr. Ian Nicholas Crispe, whose specialty is immune responses in the liver and who also works on experimental hepatitis. The activation of the immune system by infection is generally to the host’s advantage. However, activated immune cells can cause disease, as in the case of viral hepatitis, and in some circumstances may even work to the advantage of the invader. Thus, Dr. Donald Sodora’s research is driven by the idea that immune activation may be a liability in infections with viruses related to HIV. Distinguishing between immune responses that are helpful and those that cause illness will be critical in inventing the next generation of vaccines.

Different sub-populations of lymphocytes in different organs.

On the left, liver lymphocytes contain NK and NK-T cells (11.5% and 6.6% respectively). In contrast, lymph node cells contain very few of those cells. This experiment is a collaboration between the Sodora and Crispe labs.