The Regulation Of Monocyte Derived Dendritic Cells (moDCs) During Allograft Rejection
Funder
National Health and Medical Research Council
Funding Amount
$110,218.00
Summary
Islet transplantation can cure type 1 diabetes, but the required drugs for immunosuppressing graft rejection have side effects. Therefore understanding how immune rejection occurs so that we can suppress in a more discreet selective way is our goal. A type of cell that is prominent during graft rejection is the monocyte derived dendritic cell. We propose that this cell is critical for orchestrating immune responses during rejection. Therefore we wish to determine how such cells are controlled.
Understanding Rapid T-cell Clearance By The Liver: A Critical Step Towards Improved Liver Transplantation.
Funder
National Health and Medical Research Council
Funding Amount
$412,134.00
Summary
The liver has paradoxical properties: it is the site of effective immune responses to pathogens, but under some circumstances, it is known to induce harmless immune responses. Poor responses can be beneficial in a transplantation setting because, in the absence of immunosuppressive drugs, liver transplants are more readily accepted than other organ allografts. Not only are liver transplants well accepted, they can induce secondary acceptance of kidney or heart grafts from the same donor that wou ....The liver has paradoxical properties: it is the site of effective immune responses to pathogens, but under some circumstances, it is known to induce harmless immune responses. Poor responses can be beneficial in a transplantation setting because, in the absence of immunosuppressive drugs, liver transplants are more readily accepted than other organ allografts. Not only are liver transplants well accepted, they can induce secondary acceptance of kidney or heart grafts from the same donor that would otherwise be rejected. However, this ability of the liver to induce unresponsiveness may allow some viruses to persist, particularly , Hepatitis B and C. Four in every five patients infected with hepatitis C develop a chronic disease due to the inability of the immune system to clear the virus. Although it is known that white blood cells enter the liver and become unresponsive, little is known about the mechanisms that prevent an effective response. The CIA s work has been at the forefront of liver immunology and transplantation by demonstrating that the architecture and vasculature of the liver, and therefore the type of unique cellular interactions taking place within it, are essential to gain an understanding of its unique immunological properties. Using the CIB s unique protocols for solid-organ transplantation in rodents, we will provide evidence for a new mechanism that occurs at very early stages after antigen encounter in the liver. We propose to unravel this mechanism using well characterised transgenic mouse models and advanced analytical technology. We will determine the role of this mechanism in liver transplantation. Our preliminary data point to a very high chance of success. This project will have important implications for transplantation studies and for the development and treatment of food allergies and chronic hepatitis C and other of immune-mediated liver diseases.Read moreRead less
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
Targeting CD40L(CD154) On Dendritic Cells For CD8 T Cell-mediated Immunity And Tolerance
Funder
National Health and Medical Research Council
Funding Amount
$558,441.00
Summary
Killer T cells fight infection but also participate in transplant rejection. Activation of killer T cells often requires helper T cells. However, in the absence of helper cells, we have found an alternative pathway by which killer cells can be activated. We will explore this new pathway in enhancing vaccine responses and in modulating transoplant rejection.
Antigen-presenting cells control immune responses. Different types of these cells do different jobs and affect different diseases. We wish to control these processes by determining how the cells live and die. In particular we are interested in controlling the local immune responses during rejection of islet transplantation, which can cure type 1 diabetes.
The Role Of Cross-reactive T Cells In Severe Lung Disease Following Viral Respiratory Infections
Funder
National Health and Medical Research Council
Funding Amount
$1,003,390.00
Summary
Why do some patients clinically deteriorate at a greater rate than others during acute respiratory viral infections despite similar or identical clinical management? One explanation is the reactivation immunity towards ubiquitous viruses that then go on to cross-react against the new respiratory pathogen leading to an overly aggressive and destructive response in the lung. We will examine this potential of existing anti-viral immune responses to exacerbate disease in lung transplantation, as suc
This research aims to understand the early developmental events in human blood cell diversi?cation that generate cells involved in oxygen transport, wound healing and protecting us from cancer and infection. The ?ndings will assist in diagnosing and treating human immune system and blood cell disorders such as leukaemia, chronic infection and autoimmunity through understanding the mechanisms of how normal, healthy blood cells are generated.
Epigenetic Regulation Of Lymphoid Cell Development And Function
Funder
National Health and Medical Research Council
Funding Amount
$631,950.00
Summary
Inflammatory diseases such as multiple sclerosis, inflammatory bowel disease and asthma are caused by unregulated white blood cells called CD4 T cells. Why certain people develop hyperactive CD4 T cells is not clear but a understanding how CD4 T cells are regulated will help inform future therapies. Our research focuses on one enzyme called G9a that modifies proteins that control immune cell function. Our goal is to define the role of this enzyme in inflammation to aid in drug development.
Do NK Cells Limit The Long Term Burden Of CMV In Older Australians And Transplant Recipients?
Funder
National Health and Medical Research Council
Funding Amount
$413,864.00
Summary
Most people are infected with cytomegalovirus at an early age. The virus is not naturally cleared from the body but becomes latent and may be reactivated by stress or inflammation. Repeated immune responses to these reactivations causes more inflammation and wears out the immune system resulting in diseases of aging (eg: cardiovascular disease). Here we investigate which aspects of the immune system can control CMV in healthy people and in renal transplant recipients. We focus on a population of ....Most people are infected with cytomegalovirus at an early age. The virus is not naturally cleared from the body but becomes latent and may be reactivated by stress or inflammation. Repeated immune responses to these reactivations causes more inflammation and wears out the immune system resulting in diseases of aging (eg: cardiovascular disease). Here we investigate which aspects of the immune system can control CMV in healthy people and in renal transplant recipients. We focus on a population of cells called natural killer (NK) cells.Read moreRead less