The Role Of CCR6 In IL-17-producing CD8+ T Lymphocyte Activation And Trafficking
Funder
National Health and Medical Research Council
Funding Amount
$514,041.00
Summary
T lymphocytes play an important role in the control of infection, but can also contribute to diseases such as autoimmune disease and cancer. This research will identify the function of a new subtype of T lymphocyte and determine whether inhibiting its function prevents disease.
Upregulation Of Chemokine Receptor Expression And Function On CD4+ T Cells In Primary And Secondary Immune Responses
Funder
National Health and Medical Research Council
Funding Amount
$469,500.00
Summary
This research will begin to determine the significance of changes in the amount of recently-discovered proteins on the surface of cells called T lymphocytes. These cells control immune responses and move throughout the body to do this. Sometimes, they are activated inappropriately and cause diseases like asthma, arthritis and multiple sclerosis and other times they need assistance for activation (vaccination). It is therfore important to understand how the movement of these cells through the bod ....This research will begin to determine the significance of changes in the amount of recently-discovered proteins on the surface of cells called T lymphocytes. These cells control immune responses and move throughout the body to do this. Sometimes, they are activated inappropriately and cause diseases like asthma, arthritis and multiple sclerosis and other times they need assistance for activation (vaccination). It is therfore important to understand how the movement of these cells through the body is controlled. A better understanding of this process shuld allow us to design better ways to control it, thereby controlling the negative aspects of T lymphocyte activation.Read moreRead less
Understanding The Mechanism And Significance Of CXCL16-mediated Protection Of Tumour Cells From CTL-induced Apoptosis.
Funder
National Health and Medical Research Council
Funding Amount
$524,520.00
Summary
This research will begin to determine the significance of changes in the amount of a recently-discovered protein on the surface of tumour cells. We have shown that an increase in expression of this protein protects tumour cells from destruction by our immune system's killer T cells. The outcome of this research could lead to a better understanding of how the immune system recognises and kills tumour cells, and ultimately, alternate vaccine strategies for tumours.
Competition For Polarity Influences Lymphocyte Signaling And Function
Funder
National Health and Medical Research Council
Funding Amount
$500,460.00
Summary
Infectious diseases caused by viruses and bacteria remain a significant health problem. CD46 is a protein on the surface of human cells that is used by a number of viruses and bacteria to enter and infect host cells. Through binding to the CD46 protein, viruses and bacteria can induce changes in immune cells, such as T lymphocytes, that affect the way our immune system responds to infection. For example, immunosuppression induced by infection with measles virus is the primary cause of the mortal ....Infectious diseases caused by viruses and bacteria remain a significant health problem. CD46 is a protein on the surface of human cells that is used by a number of viruses and bacteria to enter and infect host cells. Through binding to the CD46 protein, viruses and bacteria can induce changes in immune cells, such as T lymphocytes, that affect the way our immune system responds to infection. For example, immunosuppression induced by infection with measles virus is the primary cause of the mortality and morbidity associated with the disease, and is a phenomenon that is poorly understood. However, there is evidence to suggest that the interaction between measles-infected cells with CD46 on the immune cells is partly responsible for the immunosuppression observed. Our laboratory has recently found that binding of CD46 (by antibody or measles antigen) on immune cells provides a signal to the cell to change its polarisation state (the way proteins are distributed within the cell) and impairs their ability to recognize and kill target cells, and become activated. These observations indicate a new paradigm by which competition of receptor signals for polarization determines signalling outcomes and provides a possible mechanism for how pathogens that bind CD46, such as measles, subvert normal immune cell communication and induce immunosuppression. This proposal aims to investigate the mechanisms behind the effect of polarising signals on immune cells, and will specifically use CD46 and measles virus as a model. The outcomes of this study will define new paradigms in lymphocyte biology and dissect the key pathways that underpin how CD46 influences immune outcome in response to infection.Read moreRead less
Regulation Of The Anti-tumour Immune Response By The Chemokine Decoy Receptor CCX-CKR
Funder
National Health and Medical Research Council
Funding Amount
$562,742.00
Summary
Melanoma is a significant cause of cancer-related deaths in Australians. Death is usually due to metastasis of the cancer to the lungs and other organs. In this project, we will take advantage of unique mouse models to determine whether inhibition of the function of a novel protein can prevent melanoma growth and metastasis to different organs. The results of this study may lead to new therapeutic approaches to control malignant melanoma and other metastatic cancers.
This project will investigate the factors that regulate the development and maintenance of a recently identified population of white blood cells called MAIT cells. MAIT cells are abundant in humans yet poorly understood. A better understanding of how these cells are regulated, and how they can be targeted in diseases, is necessary if we want to ultimately use these cells for immunotherapy.
Antigen Receptor Sharing By Lymphocytes During An Immune Response
Funder
National Health and Medical Research Council
Funding Amount
$286,328.00
Summary
A successful immune response relies on the ability of immune cells to quickly mount a specific offensive against invading foreign pathogens like bacteria or viruses. The specificity of this offensive is governed by receptors that can recognise pathogens. To survive an infection the immune system must rapidly expand the number of immune cells that have receptors that recognise, and can therefore specifically combat, the infection. The underlying theory of immunology, the clonal selection theory, ....A successful immune response relies on the ability of immune cells to quickly mount a specific offensive against invading foreign pathogens like bacteria or viruses. The specificity of this offensive is governed by receptors that can recognise pathogens. To survive an infection the immune system must rapidly expand the number of immune cells that have receptors that recognise, and can therefore specifically combat, the infection. The underlying theory of immunology, the clonal selection theory, states that this expansion is mediated by the proliferation of immune cells selected on the basis of expressing a pathogen specific receptor. We hypothesise that in addition to this proliferation the immune system may also expand the number of immune cells expressing pathogen-specific receptors by transferring these receptors between cells by a means of cell-membrane sharing. Indeed, we have evidence that this does occur both in the test tube and in animals and can function to amplify the number of immune cells that can specifically recognise a pathogen and thereby help with immune response development. This grant aims to further advance our understanding of this novel phenomenon.Read moreRead less