Skin frequently represents the first point of contact with pathogens and allergens, but there is still very little known about the role of the surface immune system in fighting unwanted invaders. Professor Graham Ogg aims to understand the role of skin immune responses by studying common skin diseases and infections.
This podcast presents the research done by Professor Ogg whilst working in the Nuffield Department of Medicine. Professor Graham Ogg now works at the Radcliffe Department of Medicine.
There are many levels in which the skin stops pathogens: first as a structural barrier, then as as focal point for both the innate and adaptive immune systems. Barrier dysfunction can lead to the development of eczema. Understanding these mechanisms can help us develop new treatments targeting the skin, as well as targeting the inflammatory response.
Ultimately, medical research must translate into improved treatments for patients. At the Nuffield Department of Medicine, our researchers collaborate to develop better health care, improved quality of life, and enhanced preventative measures for all patients. Our findings in the laboratory are translated into changes in clinical practice, from bench to bedside.
Q: How does the surface immune system on our skin stops pathogens?
GO: There are many levels in which the skin stops pathogens. The first is the structural barrier function of the skin: when we scratch ourselves that acts as a focal point for infection, so the structural physical presence of the skin is very important. Some pathogens will get past that point and that then activates components of the immune system that is split into the innate and adaptive immune responses. The innate immune response is ready to go in the skin, it can work very quickly and it works very broadly against different types of pathogens. There are molecules that are important in the innate immune system, and cells that are important. Molecules include antimicrobial peptides which can bind and inactivate different viruses, bacteria and fungi. In fact these are being harnessed for new potential antibiotic treatment in the future. Cells of the innate immune system include macrophages, natural killer cells, neutrophils and these all have broad anti-pathogen effects. But sometimes the pathogens get past the innate immune system and that’s when the adaptive immune system is activated. This is a very powerful component of the immune response. It’s very specific so an immune response to one bacterium won’t be effective against another bacterium; it’s highly specific but very powerful. It’s very costly for the host to make such an adaptive immune response but nevertheless when pathogens have passed these various levels of defence, it is activated and helps control the further replication of the pathogen. Again there are molecules and cells that are important. Molecules amongst others include antibodies; antibodies bind pathogens, bind bacteria, bind viruses and that inactivates them. Cells of the adaptive immune system include T cells and B cells; these cells help coordinate all aspects of the immune response both the adaptive and the innate immune responses.
Q: What happens when these mechanisms don’t work anymore?
GO: That’s one of the areas we’re investigating: one area of interest in our laboratory is the pathogenesis or the cause of eczema. It’s becoming increasingly clear that one of the first steps in somebody developing eczema is that there might be relative barrier dysfunction of the skin. If there’s barrier dysfunction, infections and allergens can enter the skin and induce an immune response which then causes inflammation in the skin which the patient notes as an inflammatory rash. These are really important questions because by understanding all the steps in the pathway through to the disease that the patient is experiencing one can identify new potential points which we can intervene and treat.
Q: Can this research help us to design vaccines?
GO: Yes, many vaccines are delivered into the skin or at least just beneath the skin and by understanding the skin immune system we hope to be able to inform new approaches to vaccination which may enhance vaccine response in the future.
Q: What are the most important lines of research that have developed over the past 5 or 10 years?
GO: I think it would be this recognition of the importance of the skin barrier in eczema disease. Until 5 or 10 years ago the prevailing belief was that it was the immune system that was primarily contributing to the disease, that differences in how people handled different challenges would explain why some people developed eczema and other people didn’t. Now there is this recognition that if there is barrier impairment, infections and other challenges can get into the skin and the immune response that we’re observing may be an entirely predictable and expected immune response in the skin. It illustrates I think the importance of understanding these steps because most of our treatments for eczema and related diseases such as asthma and hay fever target the immune system. It may be that we’re missing a trick here, that we should be targeting the skin, the barrier function of the skin and also the lungs and the bowels as well for food allergy as well as targeting the inflammatory response. I think in the next 5 years or 10 years there will be new treatments which are more focused on targeting the linings: the lungs, the skin and the bowels.
Q: Why does your line of research matter, why should we put money into it?
GO: Eczema is very common; it affects 20-30 % of children and is associated with asthma and hay fever and food allergies. These carry an enormous burden for families, children affected and also an enormous health economic implication for the NHS and these are very broad common diseases of which there is an unmet clinical need.
Q: How does your research fit into translational medicine within the department?
GO: The research that we do is very close to the patients; I’m a dermatologist and I see patients each week. With patients’ consent they kindly give samples, blood samples, in which we analyse the immune response. The findings that we develop in those studies we then translate back to new clinical studies for the patients.