Unlocking the secrets of the immune system

A team of scientists within the College of Life Sciences is attempting to better understand the 'nuts and bolts' of the human immune system in the hope that it may lead to improvements in vaccination and in the treatment and prevention of a variety of different illnesses and conditions from allergies to cancer.

With major funding from the Wellcome Trust and a new £2.3 million grant from the Medical Research Council, Professor Colin Watts and his team in the Division of Cell Biology and Immunology are developing their research into how the immune system works at a fundamental level and how it can be better controlled.

'The work we do could have an impact in lots of different areas of medicine,' explained Professor Watts, Chair of Immunobiology. 'We're trying to understand the nuts and bolts of the immune system and if we can do that then we will be better able to control it.'

'We're interested in how a healthy immune system operates and reacts to foreign invaders such as bacteria, viruses and vaccines but also the way the immune system reacts to transplants and what happens in autoimmune diseases such as rheumatoid arthritis and in allergies.'

Both the Wellcome Trust and MRC awards are funding five-year programmes of research with the former focussed on key enzymes called proteases which control many aspects of immunity. For example they generate small protein fragments called peptides, the 'currency' that white blood cells called T lymphocytes recognise and respond to when displayed to them on 'antigen presenting cells'.

'One of our longer term aims here is to engineer vaccines so that they are more efficiently processed and presented to T cells. That might allow limited vaccine supplies to go much further,' said Professor Watts, who began his career as a cell biologist but decided to concentrate on immunology after moving to Dundee more than 20 years ago.

The new MRC grant, awarded earlier this year, is specific funding for work on a key group of antigen presenting cells known as 'dendritic cells.'

These cells act as messengers in the body, travelling long distances from body tissues to raise the alarm if an infection has occurred. T lymphocytes then make the appropriate immune response using the information that dendritic cells provide them with.

'This is an area which we and many labs around the world are examining in great detail,' said Professor Watts. 'Immunologists agree that better understanding of how dendritic cells work will help in the design of more effective vaccines which trigger the right type of immune response. There is no doubt that vaccines are going to become more and more sophisticated as we learn how to exploit the special properties of dendritic cells.'

'Better immune responses might then be generated against both infectious agents and also perhaps against cancerous cells. There is clear evidence that the immune system can kill cancer cells and dendritic cells are already being tested in patients to 'kick-start' an anti-cancer response. In fact translation from lab bench to bedside has been particularly rapid in this area. Some early results with this type of 'dendritic cell therapy' are encouraging but it is clear that more basic information on these cells is needed for this approach to fulfil its potential.'

Professor Watts, who was elected a Fellow of the Royal Society in 2005 and is currently on the Editorial Board of the world's leading scientific journal, Science, added that the recent introduction of the Human Papillomavirus (HPV) vaccination programme to protect young women from cervical cancer was an example of how the immune system could be encouraged to respond against cancer.

'HPV causes cervical cancer and this vaccine against HPV is really the first effective vaccine against cancer so it is a good example of what can be achieved.'

Although both the Wellcome Trust and MRC grants are aimed at unlocking vital information which could ultimately result in wider practical applications in healthcare Professor Watts emphasises that his team's research is focussed on a detailed investigation of the immune system at the molecular and cellular level.

'We need to understand what is going on at a fundamental level during an immune response," he said. "It is by understanding how the system of capture, processing and presentation works, that we may then be able to make vaccines more effective or create new opportunities to intervene when the immune system is switched on inappropriately - such as in allergy, rejection of transplants or autoimmunity.'

'Our Wellcome Trust and new MRC funding reflects the progress we've made and how important this area of immunobiology is proving to be. It gives the lab continuity and the flexibility to take advantage of new developments. My scientific style has always been quite opportunistic. If a problem looks interesting and important and I think we have the tools and expertise to make a serious contribution we will start working on it, even if it is a new area for us. That is how I started working in immunology with no background in it. Of course, pretty soon we need to start collaborating with people with complementary skills and key materials.'

'The funding we currently have is also a great tribute to the outstanding colleagues who work with me and the new MRC award will benefit not only our laboratory but also, through the new Research Council funding arrangements, the University more generally.'