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ScienceWise - May/Jun 2007

Trying to understand what T cells see in viruses?

Article Illustration
Dr Tscharke and colleagues working in a sterile hood

How genetically engineered viruses might help fight infections and cancer

The human body with its regulated temperature and rich supply of nutrients offers the perfect environment for invading microorganisms to potentially flourish, so to keep us healthy we need multiple layers of defense against them. Some of these defenses are simple but effective physical barriers like the skin or mucous membranes. However when inevitably bacteria or viruses do get inside, we rely on out highly complex immune system to fight the infection. The front line troops of the immune system are lymphocytes, a class of white blood cells. There are several different types of lymphocyte in the mammalian immune system, each with a specialised role. Some work by recognising foreign proteins on the surface of cells others simply kill any cells that don’t carry our own personal marker proteins.

During an infection the immune system generates millions of lymphocytes targeted to the proteins particular to a given pathogen. After the infection is destroyed, a few of these specially adapted cells remain in the body as memory cells, enabling the system to fight similar infections much more effectively second time round. It is the action of this immune memory that forms the basis for successful vaccination.

The practice of vaccination dates back to the eighteenth century physician Edward Jenner. Jenner noticed that milkmaids, who by the nature of their occupation were highly prone to a harmless illness called cowpox, almost never contracted deadly smallpox. Modern immunologists know that smallpox, cowpox and vaccinna are all derived from a common ancestor and therefore strongly interrelated. By infecting patients with cowpox, Jenner was able to dramatically reduce their chances of later developing smallpox. Two centuries of immunisation has successfully seen smallpox eradicated as a human disease and scientists have been successful in developing numerous other vaccines to a range of illnesses. Nonetheless, there have always been a number of immune related diseases that have traditionally been unable to be treated in this way.

However, with the emerging science of genetic engineering, scientists are hopeful that genetically engineered versions of vaccinna may be able to fight a whole range of other diseases ranging from HIV to many types of cancer. The basic concept is that extra DNA is added to the vaccina genome which programs it to produce additional proteins characteristic of other organisms. When the harmless vaccinna infection runs through the body, the immune system responds and builds up memory cells and thus immunity to both vaccinna and the additional “cargo” genes. However as so often is the case in science, this elegant sounding idea is a lot more difficult to accomplish in practice. The problem tends to be that the immune system’s T cells are not equally sensitive to all the various foreign proteins and in some cases are not sensitive to them at all. It’s still a puzzle to scientists why our T cells are only tuned to perhaps 10% of the viral proteins that might potentially be used to identify an infected cell.

Dr David Tscharke of the ANU School of Biochemistry & Molecular Biology works at the interface of virology and immunology building up an understanding of the mechanisms involved in T cell activation. Dr Tscharke and his coworkers have recently been successful in identifying all 40 of the vaccinna antigens visible to human T cells. Whilst this can’t explain why the T cells only see this small subset of the vaccinna proteins, it does represent a ground breaking step in better understanding the immune response mechanism. Dr Tscharke explains that “unless you are able to monitor the immune response to the entire range of proteins, it’s very difficult to eliminate guesswork from your models.”

As has so often proved to be the case in science, researchers are hopeful that an improved basic understanding of the underlying mechanisms of immune response, will open the door to much improved treatments.

Quite apart from developing a better understanding of the underlying mechanisms of immune response to vaccinna, Dr Tscharke has a very practical interest in the pox family. Although small pox has been eradicated from the world, the battle between viruses and the immune system is not a static thing. A new variant of the pox virus family, Monkeypox, is being increasingly seen as an emergent disease. Monkeypox caries with it a variety of threats. In humans it can be almost as deadly as smallpox but unlike small pox, monkeypox is also carried by animals. This makes it’s eradication by vaccination almost impossible. It is vitally important to understand as much as possible about pox family viruses so that future threats, such as Monkeypox can be effectively dealt with.

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