Chemokine Mediated Collaboration Between T Cells And Dendritic Cells During Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$342,384.00
Summary
The immune system protects us from foreign pathogens by using multiple immune cell types. Immune cells need to migrate and interact with each other in order to function properly. When immune cells fail to migrate appropriately, autoimmune diseases or immunodeficiency may develop. By understanding the molecules regulating their migration, we can promote or inhibit immune cell function.
Role Of The Thymus In T Cell Homeostasis During Foetal And Postnatal Life In Sheep
Funder
National Health and Medical Research Council
Funding Amount
$264,750.00
Summary
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 cells, has considerable implications for the development of a pool of T cells able to respond to a large number of infections. Recent thymic emigrants represent a wide diversity of positively selected thymocytes exhibiting newly arising T cell specificities, but mature T cell pool e ....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 cells, has considerable implications for the development of a pool of T cells able to respond to a large number of infections. Recent thymic emigrants represent a wide diversity of positively selected thymocytes exhibiting newly arising T cell specificities, but mature T cell pool expansion results in reduced diversity because of a predominant expansion of a limited number of clones. It follows that a mixing of the pool of older mature T cells with new ones just released from the thymus will introduce more variability, and hence greater adaptability into the immune system. We have developed techniques for labeling the thymus in vivo and the entire blood leukocyte pool in vivo using the long-term lymphocyte tracking dye CFSE. We can establish a cohort of labeled cells and we can, for the first time in any experimental system, track directly the survival, death or division of recent thymic emigrants and mature cells and their progeny together with their tissue homing properties and surface markers for periods of many months. 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
Dendritic Cell Function, Migration And Modulation In A Murine Model Of Inflammatory Arthritis
Funder
National Health and Medical Research Council
Funding Amount
$201,870.00
Summary
Rheumatoid arthritis (RA) is a debilitating disease that affects the joints and other tissues. While it can often be controlled with drugs, complete remission off treatment is rare. Dendritic cells are the educators of the immune system. By displaying antigen to T cells they communicate the response that the immune system should make to foreign organisms, tumors and to self. Therefore, a communication failure may result in chronic inflammation, tumor growth or autoimmune disease, such as RA. In ....Rheumatoid arthritis (RA) is a debilitating disease that affects the joints and other tissues. While it can often be controlled with drugs, complete remission off treatment is rare. Dendritic cells are the educators of the immune system. By displaying antigen to T cells they communicate the response that the immune system should make to foreign organisms, tumors and to self. Therefore, a communication failure may result in chronic inflammation, tumor growth or autoimmune disease, such as RA. In this proposal, we focus on the role of dendritic cells in a mouse model of RA and explore ways of using dendritic cells to turn off disease, that if successful may translate in humans to induction of remission.Read moreRead less
Influence Of TNF And TGF-beta On Langerhans Cell Mobilisation From Regressor And Progressor Skin Tumours
Funder
National Health and Medical Research Council
Funding Amount
$227,036.00
Summary
Skin cancer is the most common type of cancer in humans. It is caused by the ultraviolet wavelengths found in sunlight. Australia has the highest incidence of skin cancer in the world, due to the large amount of sun exposure experienced by Australians during work and leisure. Considerable research needs to be directed towards this disease to understand how it forms and how it can be treated. Skin cancer can be controlled by the immune system, which in some cases is able to destroy the cancer, so ....Skin cancer is the most common type of cancer in humans. It is caused by the ultraviolet wavelengths found in sunlight. Australia has the highest incidence of skin cancer in the world, due to the large amount of sun exposure experienced by Australians during work and leisure. Considerable research needs to be directed towards this disease to understand how it forms and how it can be treated. Skin cancer can be controlled by the immune system, which in some cases is able to destroy the cancer, so that it disappears, or regresses. Other skin tumours fail to be destroyed by the immune system and therefore grow progressively. Differences between progressor and regressor tumours can help define why the immune system is able to destroy some but not other tumours. The cell of the immune system that is responsible for initiating immune responses against skin cancer is called the Langerhans cell. This cell migrates between the cancer and the local lymph node, where it activates lymphocytes to leave the lymph node and destroy the cancer. Our studies have shown that a major difference between progressor and regressor skin tumours is the ability of Langerhans cells to migrate from these tumours. Skin tumours produce cytokines (hormone like molecules) which enhance or inhibit Langerhans cell mobilization from the tumour. We have identified some of the cytokines involved, and plan to study how these cytokines interfere with this process and whether they do this by increasing the production of other factors, or by having a direct influence on the Langerhans cells. This knowledge would increase our ability to utilize these cells for treatment of cancer. This study will also further basic understanding of the biological factors which regulate the movement of this important cell from our tissues to the draining lymph node, which is of fundamental importance in the development of immunity.Read moreRead less
Polarity Regulation In T Cells: Mechanisms And Consequences.
Funder
National Health and Medical Research Council
Funding Amount
$542,462.00
Summary
Advances in our understanding of how the immune system works have led to many breakthroughs in healthcare, including organ transplantation, management of autoimmune diseases and immunodeficiencies such as AIDS. To improve these treatments, we need a better understanding of how the immune system is controlled. This proposal explores the mechanisms by which immune cell signalling is regulated by spatial compartmentalisation within the cell.
Interplay Of Innate And Adaptive Immunity To Influenza A Virus
Funder
National Health and Medical Research Council
Funding Amount
$555,693.00
Summary
Influenza is an acute febrile respiratory illness caused by influenza virus infection, and may trigger potentially life-threatening complications especially in the young and elderly. Immunity against influenza virus involves integration of the innate and adaptive immune system. We will use cutting-edge 2-photon microscopy to determine the orchestration of innate and adaptive immune cell interactions during viral infection. Results may provide for enhanced therapeutic or protective measures.