The Generation, Fate And Functional Potential Of Recent Thymic Emigrants
Funder
National Health and Medical Research Council
Funding Amount
$318,856.00
Summary
A particular kind of white blood cell, called a T lymphocyte, is responsible for controlling our immune responses to foreign invaders. These cells develop in the thymus, where they learn to distinguish between foreign invaders and self tissue, before emigrating to other organs. The regulation of this process is important to maintain a pool of T lymphocytes in the body. It is important that T lymphocytes do not respond against self tissue, as this can lead to a Oself destructO disease called auto ....A particular kind of white blood cell, called a T lymphocyte, is responsible for controlling our immune responses to foreign invaders. These cells develop in the thymus, where they learn to distinguish between foreign invaders and self tissue, before emigrating to other organs. The regulation of this process is important to maintain a pool of T lymphocytes in the body. It is important that T lymphocytes do not respond against self tissue, as this can lead to a Oself destructO disease called autoimmunity. Since these developing T lymphocytes will not see all kinds of self tissue while in the thymus, we propose that their education to prevent self-tissue reactivity may continue for some time after they leave the thymus.Read moreRead less
THE ROLE OF TUMOUR-EGRESSING T CELLS IN ANTI-TUMOUR IMMUNE RESPONSES
Funder
National Health and Medical Research Council
Funding Amount
$603,333.00
Summary
Immune cells can play both beneficial and detrimental roles in cancer. We have devised a novel method to ‘tag’ immune cells inside tumours and follow their fate. Using this method we discovered that immune cells called T cells can leave primary tumours and migrate to lymph nodes. The aim of this project is to investigate the role of these tumour-egressing cells in tumour immunity and to determine whether their migration and function can be manipulated to improve anti-tumour therapies.
The Cellular And Molecular Basis To The Paradox Of Positive Versus Negative T Cell Selection
Funder
National Health and Medical Research Council
Funding Amount
$278,090.00
Summary
The protection against disease requires the generation of white blood cells called T lymphocytes that are produced in the thymus. Each T cell has a specific surface receptor, generated by random gene switching, that can react against foreign pathogens. Since there is a very high conservation of molecules used in all organisms, some of these receptors could by chance also react against normal cells in the host. Eliminating all such self-reactive cells would mean, however, the repertoire remaining ....The protection against disease requires the generation of white blood cells called T lymphocytes that are produced in the thymus. Each T cell has a specific surface receptor, generated by random gene switching, that can react against foreign pathogens. Since there is a very high conservation of molecules used in all organisms, some of these receptors could by chance also react against normal cells in the host. Eliminating all such self-reactive cells would mean, however, the repertoire remaining for eliminating infection would be too low and immunodeficiency develops. This project investigates the mechanisms controlling the balance between defence infection and the need to prevent immune-based self destruction termed autoimmunity.Read moreRead less
Refugee Youth,Social Inclusion And Health: Social Networks, Education And Employment
Funder
National Health and Medical Research Council
Funding Amount
$108,234.00
Summary
The objectives of this research are to contribute to a deeper understanding of the issues of social inclusion for newly-arrived adolescent refugees in Australia by exploring the nature and extent of the social networks they experience. It will also assess the impact on social connectedness and socioeconomic disadvantage of an innovative program aimed at enhancing educational and employment opportunities for young people with refugee backgrounds.
Changes In The Fate Of Thymic Emigrants During Foetal And Postnatal Development In Sheep
Funder
National Health and Medical Research Council
Funding Amount
$62,744.00
Summary
SIGNIFICANCE The mature T cell pool can arise from only two sources, either thymic export or expansion of the peripheral T cell pool or a mixture of both. The lifespan of either cell type, i.e. recent thymic emigrants or mature T cell, has considerable implications for the development of the T cell repertoire. Recent thymic emigrants represent a wide diversity of positively selected thymocytes but mature T cell pool expansion results in reduced diversity because of a predominant expansion of a l ....SIGNIFICANCE The mature T cell pool can arise from only two sources, either thymic export or expansion of the peripheral T cell pool or a mixture of both. The lifespan of either cell type, i.e. recent thymic emigrants or mature T cell, has considerable implications for the development of the T cell repertoire. Recent thymic emigrants represent a wide diversity of positively selected thymocytes but mature T cell pool expansion results in reduced diversity because of a predominant expansion of a limited number of clones. A high rate of continuous substitution of mature T cells in the peripheral pool with freshly arriving recent thymic emigrants exhibiting newly arising TCR not previously existing will produce higher adaptive capabilities for the immune system. We have developed techniques for labeling the thymus in vivo by intra-thymic injection with the long-term lymphocyte tracking dye CFSE. We can establish a cohort of labeled recent thymic emigrants and we can, for the first time in any experimental system, track directly the survival, death or division of recent thymic emigrants and their progeny together with their tissue homing properties and surface markers for periods of many months after they leave the thymus. This will enable us to determine the way in which the pool of mature T cells is built up during the formation of the foetal immune system and the way the mature T cell population is established and maintained in postnatal life.Read moreRead less
DETERMINING THE ROLE OF ER STRESS INDUCED APOPTOSIS IN THYMIC NEGATIVE SELECTION
Funder
National Health and Medical Research Council
Funding Amount
$558,189.00
Summary
Apoptosis is an evolutionarily conserved mechanism for killing unwanted cells that are no longer needed, damaged, infected with pathogens or dangerous. Defects in apoptosis can cause a number of diseases. For example, abnormal survival of cells can cause cancer or autoimmune disease. Bim is a protein that induces apoptosis and act as a barrier against cancer and autoimmune diseases. This work is aimed at understanding how Bim acts as a barrier against the development of autoimmunity.