Immunological Studies Of Adjutant Induced Arthritis
Funder
National Health and Medical Research Council
Funding Amount
$412,104.00
Summary
This project stems from our interest in rheumatoid arthritis and a number of other forms of arthritis that affect many joints in a symmetrical fashion (the polyarthritides). In most instances, there is evidence that the diseases are caused by an attack on the joint lining (the synovium) by cells of the immune system. Rheumatoid arthriis is the most common and often the most severe of the polyarthritides. Neither the triggering event nor the target of the attack by the immune system is understood ....This project stems from our interest in rheumatoid arthritis and a number of other forms of arthritis that affect many joints in a symmetrical fashion (the polyarthritides). In most instances, there is evidence that the diseases are caused by an attack on the joint lining (the synovium) by cells of the immune system. Rheumatoid arthriis is the most common and often the most severe of the polyarthritides. Neither the triggering event nor the target of the attack by the immune system is understood and as a result, there are no specific preventative measures against the disease or specific therapies for the established disease. There is, however, strong evidence that the cells involved in the attack on the synovium are orchestrated by a white blood cell called the T lymphocyte. T lymphocytes cannot operate alone but require a second cell, the dendritic cell, to present the target in a special way which can be recognised and responded to by the T lymphocyte. The T cell and the dendritic cell are the two central aspects of this project. We will use an animal model of polyarthritis to allow access to these cells during the earliest phases of the disease, a silent period not recognisable in the earliest stages of rheumatoid arthritis. T lymphocytes from animals with experimental polyarthritis will be used as indicators in the search for the target of the disease process and dendritic cells from affected joints will be used as a natural source of that target. By the production of highly specific T lymphocytes (members of clones), we hope to identify the target molecules of the disease process. This information should lead ultimately to the identification of the triggering stimulus (and thence prevention) and to the development of highly specific therapies designed to treat the established disease.Read moreRead less
The Immunological Microenvironment In The Synovium During Experimental Polyarthritis In The Rat
Funder
National Health and Medical Research Council
Funding Amount
$473,250.00
Summary
In this project, we aim to understand the process by which some forms of arthritis, as exemplified by rheumatoid arthritis (RA), cause inflammation and destruction of multiple joints. Such forms of arthritis are referred to collectively as polyarthritis. There is a strong evidence that RA has an immunological basis and that abnormal recognition of components of the joints by T lymphocytes orchestrates the inflammation that is characteristic of the disease. We believe that dispersal of disease-ca ....In this project, we aim to understand the process by which some forms of arthritis, as exemplified by rheumatoid arthritis (RA), cause inflammation and destruction of multiple joints. Such forms of arthritis are referred to collectively as polyarthritis. There is a strong evidence that RA has an immunological basis and that abnormal recognition of components of the joints by T lymphocytes orchestrates the inflammation that is characteristic of the disease. We believe that dispersal of disease-causing activated T lymphocytes in the blood accounts for the involvement of many joints. We have used a model of polyarthritis in rats to study the nature of the activated T lymphocytes, where they come from, how they are delivered to the blood stream and how they enter the joints. This project focuses on the crucial tissues that line the joints. We want to understand how the disease-causing activated T cells cause inflammation and how the immune system reacts to restrain them. We can undertake this work because we have developed three unique tools. Firstly, we can transfer arthritis with activated T lymphocytes and, therefore, study their behavior in an otherwise normal body. In this way, we can see how the body responds to the presence of disease causing cells. Secondly, we have introduced a genetic marker, which is essential if one wishes to distinguish the separate activities of the donor' and host cells. Thirdly, we can collect cells from the diseased paws, allowing us to examine their activities in vitro as well as in vivo. This model offers the opportunity to study the activities of the disease-causing cells and to identify points at which the disease cycle can be broken. It will allow us to design and-or test new treatments aimed at these points.Read moreRead less
The Impact Of Obesity On Immunological Tolerance Of The Fetus
Funder
National Health and Medical Research Council
Funding Amount
$378,366.00
Summary
Obesity increases the risk of miscarriage during pregnancy. The reasons for this are not known, although it is thought that abnormal levels of hormones and metabolic parameters are a contributing factor. We hypothesise that the immune system plays a role. In this project we will determine if obesity upsets the fine-tuning of the immune system that is crucial for successful pregnancy. Understanding the reason behind adverse pregnancy outcome will allow appropriate management of maternal obesity.
The Molecular Determinants Of Immunological Tolerance
Funder
National Health and Medical Research Council
Funding Amount
$473,477.00
Summary
Autoimmune diseases, such as type I diabetes and multiple sclerosis, are debilitating disorders that impose a massive toll on wellbeing in Australia and worldwide. This fellowship will support research aimed at determining the genes and mechanisms that control autoimmunity. New technologies will be brought to bear to track immune cells throughout their development, maturity and malfunction in disease settings. We aim to uncover new therapeutic targets to prevent and reverse autoimmune disease.
This application seeks information on the factors controlling T cell survival, tolerance and responsiveness to foreign antigens and tumour antigens. Particular attention will be directed to determining how T cells are kept alive through contact with self ligands and cytokines while preserving self tolerance and how anti-tumour responses can improved without augmenting the function of T regulatory cells.
Cancer is one of the leading causes of death in the industrialized world. While therapies to treat cancer have continued to improve one area that, in theory at least, shows great promise in the treatment of tumours is manipulating the immune system to effectively recognize and destroy cancerous lesions. Experiments in human and animal systems have clearly shown that the immune system has the potential to respond to tumour cells and trials of tumour vaccines are underway. It has recently become a ....Cancer is one of the leading causes of death in the industrialized world. While therapies to treat cancer have continued to improve one area that, in theory at least, shows great promise in the treatment of tumours is manipulating the immune system to effectively recognize and destroy cancerous lesions. Experiments in human and animal systems have clearly shown that the immune system has the potential to respond to tumour cells and trials of tumour vaccines are underway. It has recently become apparent that the immune responses to tumours may be inhibited by classes of regulatory immune cells. Eliminating these cells results in a more vigorous and effective anti-tumour response. This project will seek to discover the mechanisms of action of theses regulatory immune cells in order to devise more effective anti-cancer vaccines and therapies.Read moreRead less