Research Theme

Immunology

The study of our immune system, known as immunology, has important implications in almost every disease. When our immune system is functioning normally we hardly notice that it exists. It protects us day and night from life threatening infections. If our immune system fails, diseases result.

An “underactive” immune system makes us susceptible to bacterial, viral and fungal infections and diseases such as cancer.  An “overactive” immune system can cause a variety of disorders such as lupus, rheumatoid arthritis and multiple sclerosis as well as hypersensitivities including anaphylaxis, asthma and atopic eczema.

There are very few diseases that do not involve the immune system, and many therapeutic approaches are aimed at boosting the immune response.

Some examples of research projects within the Immunology research theme at the Menzies Research Institute:

Switching on gene expression in T cells: The role of NF-kB recruited SWI/SNF chromatin remodelling complexes in inducible gene expression in T cells

Cells within the immune system are activated to fight infection by producing a host of signalling molecules called cytokines. Immune diseases arise when these cytokines are not produced at the correct time and place. This project aims to determine how cytokine genes are produced in response to immune signals.

We have identified important components of the gene switch that is required to produce a cytokine called GM-CSF in immune cells. We have found that particular tags or marks are associated with this cytokine gene in immune cells which allow it to be switched on rapidly in these cells. These tags are not associated with the gene in cells where it does not need to be switched on. In addition we have found that some of these tags are also associated with other immune cytokines, suggesting a common mechanism by which cytokines can rapidly orchestrate a response to infection.

Long Term Effects of UV-B Irradiation on the Developing Skin Immune System

Exposure to sunlight, which includes ultraviolet radiation, during early childhood has been linked to the development of skin cancer later in life. We believe that this is due to differences in the immune system of adults compared to very young children, and that this influences the response to the ultraviolet radiation. This project aims to analyse the immediate and long term effects of ultraviolet radiation on the immune system of neonatal mice, with the aim of scientifically demonstrating a link between neonatal exposure to ultraviolet radiation and skin cancer development.

This study demonstrated that exposure to a single “sunburn” in early life does disrupt the development of the skin immune system. When the mice in this study reached adulthood, cells within lymph nodes were significantly altered as there was an increase in the population that controls the immune response, namely T regulatory and B cells. These results clearly show that inappropriate exposure to sunlight at a very young age can alter the immune response in adulthood.

The Skin Immune System in Cutaneous Carcinogenesis

Vitamin D is produced in the skin in response to exposure to sunlight. As excess sunlight can contribute to the development of skin cancer we assessed how the skin immune system and skin cancer development was influenced by vitamin D. To do this we analysed the effects of vitamin D deficiency throughout life to determine if vitamin D deficiency in mice impairs the development and function of the skin immune system as well as increasing the susceptibility to sunlight induced skin cancer.

The outcomes to date indicate that males and females respond to different extents to vitamin D. When analysing the function of the skin immune system it was found that vitamin D controls its function of skin immune system more effectively in males than in females. However, when analysing the role of vitamin D in protecting against sunlight induced skin cancer we produced evidence to indicate vitamin D is more effective in females than in males. The role of vitamin D may explain why females are more prone to autoimmune disease but less prone to skin cancer than their male counterparts.

Skin Immune System: From Birth to Maturity

In early life we have an immature immune system and we are susceptible to various infections. The local environment in which the cells reside will influence the development of the immune system, therefore this project used the skin immune system as a model to understand how the immune system develops and the influence of the environment. This was undertaken by analysing the proteins and cells during development.

A detailed “map” of all the proteins which are present in adult and neonatal skin has been produced and when comparing these “maps” a number of proteins have been identified that may guide the development of the skin immune system. One of these proteins, Stefin A, has been evaluated in more detail, as it appears to be critical to development of the skin immune response. Using human skin we have been able to produce a model of how immune cells interact in the early stages of development and how this may direct outcomes of immunity in later life.

Immune Response of the Tasmanian Devil

The Tasmanian Devil is currently under threat from a devastating disease known as Devil Facial Tumour Disease (DFTD).  A remarkable feature of this disease is that it is directly transferred between devils. As there is no evidence for lymphocyte infiltration into the tumour it would indicate a lack of immune involvement and poses the possibility that the immune system of the devil is suppressed. In order to evaluate this we analysed aspects of the immune response of the Tasmanian devil as well as analysing the tumour for factors that may suppress the immune response.

This study has clearly shown that the Tasmanian devil has a healthy immune response and that the tumour does not produce a factor to suppress the immune response. By performing studies on lymphocytes from devils from around the state we have good evidence to indicate that there is a limited genetic diversity among the devil population hence the tumour is not recognised and eliminated by the immune system.

Evaluation of Natural Products on the Immune Response and Other Related Health Parameters

For more information, contact:

Associate Professor Greg Woods

Member

Telephone: (03) 6226 4832

Fetal and infant determinants of childhood asthma

The Tasmanian Infant Health Survey is an important international resource with regard to obtaining better information on the fetal, infant and child determinants of allergic disease, including asthma.

In 2006, a paper on the possible programming effects of antenatal diet on child size, shape and body composition at birth was prepared and published. Further work on to evaluate the possible adverse effects of very early introduction of a range of foods and drinks was conducted and is now in press.

Early life factors and allergic disease in adolescence

The T-Bone Study included measures on hayfever and allergic development in adolescents. This allows us to take a ‘life course approach’ to study allergic disease causation, looking at not only fetal and infant factors but also those likely to be acting when children are of primary school age.

In 2006, extensive data analysis was conducted on allergen-pollen interactions, risk factors for peanut and other food allergy and other issues.

For more information, contact:

Professor Anne-Louise Ponsonby

Senior Member

Telephone: (03) 6226 7700