Unlocking the secrets of the immune system


Professor James McCluskey

07 October 2011

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Voice-over: Welcome to this National Health and Medical Research Council podcast.

Our podcasts aim to keep you in touch with major health and medical research issues and the people who shape them.

Introduction: Hello I’m Carolyn Norrie of the NHMRC. I’m speaking today with Professor Jim McCluskey, program grant winner of Melbourne University. Professor McCluskey’s work is in antigen presentation, recognition and the immune system.

Hello Jim.

Prof. McCluskey: Hello Carolyn how are you?

Interviewer: I’m good. I’d like to ask you how does the immune system work?

Prof. McCluskey: Well the immune system has two parts to it, one is the part that reacts to foreign agents in a fairly non specific way …so if you cut yourself or get a splinter you’ll get a swelling and inflammation and that’s called the innate immune system. The other part is the specific immune system and that’s the part we work on …that’s much more customized and tailored towards recognising very specific and particular microbes. We work on how that recognition takes place, what is actually recognised and how the cells of the immune system that protect us from infection are activated following that recognition.

Interviewer: So how does the recognition take place?

Prof. McCluskey: The T-cells and B-cells of the immune system have on the surface of their membrane, very specific receptors. The part we work on are the receptors on T-cells. T-cells are often called the conductors of the immune orchestra because they actually regulate antibody production and they kill infected cells and make factors called cytokine that regulate immunity so how T-cells recognise microbes is enormously interesting to us and they have very specific receptors that can recognise fragments of micro-organisms.

Interviewer: So it’s obviously an extremely complex process. Where is your research focused?

Prof. McCluskey: A big part of our program is focused on how the dendritic cells work and it turns out that not all dendritic cells are the same… there’s a family of these and they each seem to have a different function and capacity. Some of them make certain cytokines that help protect against viruses, others are more specialised in activating killer T-cells and there even seems to be a kind of a relay team function amongst dendritic cells so that some of the dendritic cells – let’s say in the skin – can capture parts of microorganisms, carry them back to lymph nodes in the spleen where the T-cells reside and then hand them to a new dendritic cells which will then show it off to the T-cell and lead to that activation. So a big part of our program is on the cellular aspects of how antigen is presented to T-cells.

Interviewer: My understanding is the dendritic cells give you some great opportunities to potentially apply this high level research to clinical health.

Prof. McCluskey: Well exactly. So this is where the translational pay off comes from our research. If we can understand which are the dendritic cells that activate killer T-cells…which are the ones that hand over antigen, which are the ones that make certain cytokines specific to particular viruses and perhaps there are even dendritic cells that might be more specialised in suppressing immunity…more specialised perhaps in inducing what we call tolerance in T-cells preventing them from reacting to antigens... then we can tailor intervention therapies, immune therapies, to target antigens to particular dendritic cells. So if you want immunity let’s say in the case of a vaccine – development against a virus- then you might target one type of dendritic cell that will activate killer T-cells. If you want tolerance then you may chose actually to target another type of dendritic cell.

Interviewer: And so the dendritic cells that lead to this tolerance have some great potential don’t they?

Prof. McCluskey: They do but we need to know whether they really exist first so we need to be sure first that there are dendritic cells that are capable of inducing tolerance and if that was the case then the capacity to potentially prevent autoimmune disease or inhibit transplant rejection or suppress unwanted allergic reaction.. this would be very powerful.

Interviewer: So that’s where you can see a real benefit coming through to not only Australians but potentially on the international scene?

Prof. McCluskey: Absolutely. Understanding these pathways and mechanisms helps us understand why different people react differently to the same virus…why some people get a terrible bout of influenza and others are protected… why some people progress with HIV and others don’t progress as rapidly…why some people get drug reactions to new drugs and others don’t. That sort of immunogenetics is part of the whole background of what we’re doing.

Interviewer: Sounds excellent so I would like to thank you for spending time speaking to us today and I hope your research goes very well.

Prof. McCluskey: My pleasure Carolyn.

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You’ll find more information about this and other health and medical research issues on our website, at www.nhmrc.gov.au.