Why Does Peripheral Airway Dysfunction Lead To Broncholitis Obliterans Syndrome In Lung Transplantation?
Funder
National Health and Medical Research Council
Funding Amount
$312,927.00
Summary
The uneven way that airways narrow (heterogeneity) is an important factor affecting the natural history, clinical expression and response to treatment in patients following lung transplantation. In the proposed study we plan to monitor the heterogeneity of the airways in patients immediately following lung transplantation and relate these changes to immunological markers of lung rejection.
The Ontogeny Of TLR Mediated Innate Immune Function In Normal And Atopic Children
Funder
National Health and Medical Research Council
Funding Amount
$463,328.00
Summary
Bacteria are first recognised by the immune system though primitive innate immune pathways which are highly conserved through evolution. The activation of these pathways is critical for the maturation of the immune system. This may explain the rise in immune diseases with cleaner environments (and less innate immune activation). We speculate that functional differences (as a result of environmental or genetic factors) are implicated in the rising rates of allergic disease. This is the first stud ....Bacteria are first recognised by the immune system though primitive innate immune pathways which are highly conserved through evolution. The activation of these pathways is critical for the maturation of the immune system. This may explain the rise in immune diseases with cleaner environments (and less innate immune activation). We speculate that functional differences (as a result of environmental or genetic factors) are implicated in the rising rates of allergic disease. This is the first study to document normal maturation of these innate pathways in early childhood, and to compare this in allergic and nonallergic children. We will do this using existing samples collected as part of previous cohort studies. This study is the logical next step in the quest to define allergy pathogenesis. Whatever the outcome, the findings will be of enormous significance. A better understanding of the development of these pathways is also likely to contribute to more avenues for better-targeted treatment and prevention.Read moreRead less
The Role Of Aire In Immunological Tolerance And Autoimmunity
Funder
National Health and Medical Research Council
Funding Amount
$434,134.00
Summary
The immune system is designed to protect us from foreign pathogens such as bacteria, viruses and parasites. This is achieved through lymphocytes which recognise foreign pathogens. However in 5-6% of the population the immune system attacks the host and induces autoimmunity. We aim to understand the mechanisms which control the production of self-reacting lymphocytes and how we may reduce the incidence of autoimmunity.
Inflammatory diseases, such as autoimmune diseases, result from an overactive immune system. A new therapy that is currently under trial is the use of special blood cells, called Treg cells, whose function is to suppress unwanted immune responses. This application evaluates the efficacy and safety of such treatments.
Crossover Trial Of Dermoscopy And Short-term Digital Monitoring For The Management Of Skin Lesions In General Practice
Funder
National Health and Medical Research Council
Funding Amount
$192,000.00
Summary
Australia has the highest incidence of melanoma in the world. Early detection of melanoma is critical in reducing the death rate from melanoma. Currently the diagnostic accuracy of melanoma in general practice is poor with around 30 benign lesions being cut out for every one melanoma. This severely impacts on the total health budget, with a cost of $46M per annum in general practice. An improved diagnostic method for detecting melanoma of the skin will allow earlier detection of melanoma and dec ....Australia has the highest incidence of melanoma in the world. Early detection of melanoma is critical in reducing the death rate from melanoma. Currently the diagnostic accuracy of melanoma in general practice is poor with around 30 benign lesions being cut out for every one melanoma. This severely impacts on the total health budget, with a cost of $46M per annum in general practice. An improved diagnostic method for detecting melanoma of the skin will allow earlier detection of melanoma and decrease the rate of needless excision biopsies.Read moreRead less
Tolerogenic Dendritic Cells In Common Marmoset Renal Transplantation
Funder
National Health and Medical Research Council
Funding Amount
$162,756.00
Summary
ORGAN TRANSPLANT PATIENTS currently need life-long immune suppressing drugs to prevent rejection, often using 15 medications a day, costing Australia $52M in 2002. These drugs increase risks of infection and cancer. 90% of patients develop some form of cancer over 30 years. They also cause non-specific side effects including high blood pressure, diabetes and osteoporosis. The average lifespan of a kidney transplant is 8-15 years. Major causes of kidney transplant loss are rejection and drug toxi ....ORGAN TRANSPLANT PATIENTS currently need life-long immune suppressing drugs to prevent rejection, often using 15 medications a day, costing Australia $52M in 2002. These drugs increase risks of infection and cancer. 90% of patients develop some form of cancer over 30 years. They also cause non-specific side effects including high blood pressure, diabetes and osteoporosis. The average lifespan of a kidney transplant is 8-15 years. Major causes of kidney transplant loss are rejection and drug toxicity. TRANSPLANTS ARE REJECTED when a recipient's immune system sees the kidney as foreign. Immune suppressing drugs prevent rejection by stopping the reaction to foreign tissues, but this causes increased infection and cancer risk. IMMUNE TOLERANCE means the recipient's immune system sees a transplant not as foreign but as part of itself, no longer reacting to it. If tolerance could be achieved for transplants, patients wouldn't need to use immune suppressing drugs. Costs of immune suppression would be nil. Tolerance is the best long-term solution for patients needing transplants. Tolerance has been achieved in various ways in mice models. DENDRITIC CELLS can be used to induce tolerance as they can silence a recipient's immune system, preventing it from seeing transplant tissues as foreign. We have shown in mice that a single infusion of a certain type of dendritic cells caused prolonged transplant tolerance without needing immune suppression. This project aims to use dendritic cells to induce tolerance in a marmoset model - a required step before allowing this therapy to be done in humans. PRIMATES like MARMOSETS have close genetic identity to humans and are ideal transplant models as their immune systems react much more like humans than other animals. Marmosets are not an endangered species and are smaller, cheaper and easier to care for than other primates. Ultimately, experiments in other species would need repeating in primates before human trials could be done.Read moreRead less
Risky spaces: Children experiencing governance across school, home and community sites. Children's lives are being increasingly governed through adult policy and practices designed to protect children, but about which children themselves have hitherto had little say. This project invites young children to account for their experiences in managing risky spaces in everyday interactions at school, home and community. Risky spaces refer to those potentially dangerous social, political and economic ....Risky spaces: Children experiencing governance across school, home and community sites. Children's lives are being increasingly governed through adult policy and practices designed to protect children, but about which children themselves have hitherto had little say. This project invites young children to account for their experiences in managing risky spaces in everyday interactions at school, home and community. Risky spaces refer to those potentially dangerous social, political and economic sites of childhood. This is the first Australian project to investigate children's understandings of these matters. Outcomes will inform national educational and social policy directions and provide strategies for educators and human service providers working with young children and their families.
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Randomized Controlled Trial Of A Video-delivered Intervention For The Early Detection Of Melanoma In Men 50+ Years
Funder
National Health and Medical Research Council
Funding Amount
$511,694.00
Summary
Unfortunately, men over 50 years are most at risk to die from melanoma. Skin self-examination, where a man inspects the skin of his whole body with the help of a mirror or another person, and rapid presentation to a doctor without delay if he detects a suspicious lesion has the potential to increase awareness for the skin and to improve early diagnosis. We want to assess if we can increase the rate of skin self-examination in men 50 years and over through a video-delivered intervention.
The Role Of Dendritic Cell Subsets In The Decision Between T Cell Tolerance And Immunity
Funder
National Health and Medical Research Council
Funding Amount
$445,009.00
Summary
The immune system protects the body against infection by means of a population of circulating white blood cells called lymphocytes. Each lymphocyte has on its surface its own particular receptor which recognises only one out of the universe of possible substances. Receptors are generated in a semi-random way, using a combination of elements encoded by the genes, and it is possible to generate receptors that react with the body itself, rather than with invading organisms. If the cells bearing the ....The immune system protects the body against infection by means of a population of circulating white blood cells called lymphocytes. Each lymphocyte has on its surface its own particular receptor which recognises only one out of the universe of possible substances. Receptors are generated in a semi-random way, using a combination of elements encoded by the genes, and it is possible to generate receptors that react with the body itself, rather than with invading organisms. If the cells bearing these self-reactive receptors become activated, an autoimmune disease ensues. The question of how lymphocytes can tell the difference between the body itself and foreign organisms is of major interest to immunologists. One of the first ideas was that self-reactive lymphocytes are inactivated by making reactions early in life. Despite the simplicity and intellectual appeal of this idea, it is inconsistent with a large body of experimental evidence. On the basis of number of new experiments, I have proposed an alternative model of self tolerance for one of the subsets of lymphocytes. In this model, the cells that help lymphocytes to recognise particular substances possess the property of distinguishing self from foreign, and pass that information on. The aim of this project is to provide direct experimental evidence in support of the model. Many of our attempts to deal with medical problems related to the immune system have been hampered by our lack of understanding of exactly how immune tolerance is controlled. If my model proves to be correct, it will be possible to manipulate immune responses with far greater effectiveness, providing new treatments for autoimmune disease, allergy, graft rejection and vaccination.Read moreRead less