Viral Antigen Presentation Kinetics And Memory T Cell Inflation
Funder
National Health and Medical Research Council
Funding Amount
$503,753.00
Summary
The ageing of the population is one of the major transformations being experienced by Australia’s population which will have major health implications. Recent studies have shown that many elderly individuals display ‘immune risk phenotype’ (IRP) which is characterised by a severely distorted immune system and human cytomegalovirus (CMV) infection. In this project we will investigate the mechanisms by which CMV alters cellular immune system and thus impacts on the host immunity against other path ....The ageing of the population is one of the major transformations being experienced by Australia’s population which will have major health implications. Recent studies have shown that many elderly individuals display ‘immune risk phenotype’ (IRP) which is characterised by a severely distorted immune system and human cytomegalovirus (CMV) infection. In this project we will investigate the mechanisms by which CMV alters cellular immune system and thus impacts on the host immunity against other pathogens.Read moreRead less
Priming, Recruitment And Retention Of Influenza Virus Specific CD8 T Cells In The Upper Airways
Funder
National Health and Medical Research Council
Funding Amount
$633,371.00
Summary
Influenza virus gains entry into the body by inhalation and initiates its replication cycle within the upper airways. This early stage of infection, when the amount of influenza virus is low, provides the ideal window of opportunity for an effective immune response to limit disease progression. In this proposal we will define the immunity that can be evoked within the upper airways and determine immune mechanisms left behind that can safeguard this region from this important respiratory pathogen
We know that many parts of viruses are displayed to the immune system, but infection can also result in the display of fragments of our body's own proteins (self-peptides). We will apply cutting-edge technology to find all the virus- and self-peptides that are recognised by the immune system during infection with a vaccine virus and influenza virus. This will help us understand how the body fights infection and perhaps why infection can sometimes start autoimmune diseases.
The Role Of NOD Proteins In T Cell Development And Function.
Funder
National Health and Medical Research Council
Funding Amount
$349,590.00
Summary
The long-term goal of this project is to understand the role of NOD proteins in the T cell branch of the immune system. Distorted T cell responses can lead to over-activation and autoimmunity, or host susceptibility to microbial infection. This project aims to provide a deeper understanding of NOD proteins in chronic inflammatory diseases like Crohn’s disease, where altered NOD signaling may generate intrinsic T cell defects, in addition to altered microbial sensing and host protection by the in ....The long-term goal of this project is to understand the role of NOD proteins in the T cell branch of the immune system. Distorted T cell responses can lead to over-activation and autoimmunity, or host susceptibility to microbial infection. This project aims to provide a deeper understanding of NOD proteins in chronic inflammatory diseases like Crohn’s disease, where altered NOD signaling may generate intrinsic T cell defects, in addition to altered microbial sensing and host protection by the innate immune system.Read moreRead less
Roles Of CD8-positive T Cells And Chemokines In Cerebral Malaria.
Funder
National Health and Medical Research Council
Funding Amount
$392,545.00
Summary
About 2 million people die each year from complications of malaria infection. The most common form of these fatal complications is called cerebral malaria. For reasons that are not fully understood, the brain of the patient becomes affected. Early after infection there are behavioural changes, progressing to coma. About 20% of people who enter coma with malaria infection, and are treated with anti-malarial drugs, die and the remainder recover, sometimes with slight neurological impairment. One t ....About 2 million people die each year from complications of malaria infection. The most common form of these fatal complications is called cerebral malaria. For reasons that are not fully understood, the brain of the patient becomes affected. Early after infection there are behavioural changes, progressing to coma. About 20% of people who enter coma with malaria infection, and are treated with anti-malarial drugs, die and the remainder recover, sometimes with slight neurological impairment. One theory to explain cerebral malaria is that is caused by the body's own immunological response against the parasite. Using an experimental model in mice, we will find out whether the immune system cells called CD8-positive T lymphocytes are important in causing the brain complications. We also will find out whether messenger molecules called chemokines are important. From this work we hope to discover better ways of treating cerebral malaria.Read moreRead less
Combining Immune Profiling And Immunotherapy To Tackle Human Cytomegalovirus Infection In Transplant Patients
Funder
National Health and Medical Research Council
Funding Amount
$314,644.00
Summary
The proposed research aims to help transplant patients who are at high risk of cytomegalovirus (CMV) infection, using a treatment called adoptive immunotherapy. I seek to improve the function of patients’ own specialised immune cells (known as T cells) in laboratory and transfer the T cells back into patients, allowing them to better fight the CMV infection. This treatment will improve survival, minimise transplant rejection and reduce the cost associated with anti-viral drugs.
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
Role Of Hepatocytes In Inducing Primary CD8+ T Cell Activation And Tolerance
Funder
National Health and Medical Research Council
Funding Amount
$159,662.00
Summary
It is well known that tolerance to liver allografts is more readily achieved than to other organ grafts, even across a major histocompatibility (MHC) barrier. According to some experiments, preferential tolerance to liver grafts may be due to development of chimerism involving the very large number of passenger leukocytes of donor hematopoietic origin present in an organ of this size. However, such a concept does not explain all the available data, particularly those relevant to CD8+ T cells, th ....It is well known that tolerance to liver allografts is more readily achieved than to other organ grafts, even across a major histocompatibility (MHC) barrier. According to some experiments, preferential tolerance to liver grafts may be due to development of chimerism involving the very large number of passenger leukocytes of donor hematopoietic origin present in an organ of this size. However, such a concept does not explain all the available data, particularly those relevant to CD8+ T cells, the primary effectors of graft rejection. Moreover, it does not take into account the fact that the liver possesses a unique fenestrated endothelium which is permeable to naive as well as activated T cells, nor the tolerogenic properties of hepatocytes themselves. Our recent experiments suggest that the liver is a site of primary activation for CD8 T cells and that a normal liver contains a significant number of self-reactive CD8+ T cells. The aim of this project is to determine whether activation of CD8+ T cells by hepatocytes contributes to the striking ability of liver grafts to be accepted and to induce tolerance in the CD8 T cell compartment. This would indicate that the liver plays an important role in peripheral tolerance of CD8+ T cells, providing the basis for novel therapies in transplantation and the treatment of autoimmune diseases. Moreover, this project also aims to generate a unique animal model of chronic liver inflammation in the absence of viral infection. Such a model is needed to study cirrhosis and hepatocarcinoma in the absence of potential oncogenes carried by viruses such as hepatitis B.Read moreRead less