Immunology

2004-2005

From left: Ken Shortman (Division Head), Gabriel Belz, Lynn Corcoran, Steve Gerondakis, Bill Heath, Phil Hodgkin, Jacques Miller, Stephen Nutt, David Tarlinton, José Villadangos & Li Wu.

• Research Focus
• Overview
• Email the Immunology Division

Research Focus

• Immune system development
• Dendritic cell function
• B cell responses

Overview

Our Division studies the immune defense system. This involves investigating the individual cells of this system, particularly the T and B lymphocytes, the NK cells and the dendritic cells (DC). We investigate their development from stem cells, by pathways related to those that form other blood cells. We investigate the ways they signal to each other, as well as the cascade of chemical signals within each cell when they are activated. We investigate their transformation into effector cells, making antibodies or cytokines, or becoming killer cells, in response to invasion by microorganisms, parasites or cancer cells. The overall aim is to learn enough about the immune system to be able to manipulate it, either to prevent or ameliorate autoimmune disease, or conversely to enhance responses to pathogens and improve vaccines.

This year has seen progress in understanding the detailed roles of several transcription factors that direct the development of immune system cells. These factors inside the cells include PU.1 which is involved in the early development of many blood cells, Rel A involved in the functioning of lymphocytes but now shown to be important for other blood cells, and OBF-1 involved in antibody production by B lymphocytes.

The developmental origin of the multiple subtypes of DC had been difficult to study, since previous culture systems for producing DC did not mimic normal development. We now have a culture system that efficiently generates from bone marrow all the DC subtypes normally found in spleen. It will now be possible to analyse the individual steps of this process. We have also shown that one particular subtype of DC has a specialised role in defence against viral infections, since it collects viral components transported by other DC, then stimulates the development of killer T cells.

Predicting the final immune response outcome when lymphocytes receive multiple stimuli is a daunting but necessary task if we hope to manipulate the immune system. By breaking the problem down into a series of “internal machines” we have been able to use computational methods to accurately predict outcomes. We are developing the models, the programmes and the software to make this approach more accessible.