DEVELOPMENT OF CLINICALLY APPLICABLE STRATEGIES TO INDUCE AND MONITOR LONG TERM ACCEPTANCE OF LIVER ALLOGRAFTS
Funder
National Health and Medical Research Council
Funding Amount
$287,036.00
Summary
Liver transplantation is the only therapy for end-stage liver disease and thousands of Australian lives have been saved with this treatment. The major complication of liver transplantation is rejection which leads to loss of about half of the transplanted livers by ten years. Liver transplants in many animal models are not rejected and function normally for the life of the animal. Using one such animal model we have shown that white cells from the donor are responsible for the absence of rejecti ....Liver transplantation is the only therapy for end-stage liver disease and thousands of Australian lives have been saved with this treatment. The major complication of liver transplantation is rejection which leads to loss of about half of the transplanted livers by ten years. Liver transplants in many animal models are not rejected and function normally for the life of the animal. Using one such animal model we have shown that white cells from the donor are responsible for the absence of rejection. Of interest, these cells appear to stimulate a rapid and extreme immune response, which closely resembles rejection. The main difference is that it is quicker and more marked than rejection and then exhausts itself. This observation is unexpected and suggests possibilities for new treatments. Furthermore it questions the effectiveness of our present treatment for rejection of transplanted livers. We have already shown that some kinds of drugs given to prevent rejection in humans actually have the opposite effect in the animal model and prevent long-term acceptance of liver transplants. The aim of this work is to develop in our animal model a better way of treating human liver transplant patients. This will incorporate injection of donor white cells and treatment with drugs which promote the beneficial effects of these cells. We will also develop ways of testing the blood or the liver of the human liver transplant patients early after transplantation to find out whether the patient is accepting the liver or not. This means that we should be able to try this new treatment method in liver transplant patients once it has been optimised in the animal model.Read moreRead less
Delineating Aberrant Adaptive Immune Responses Due To Germline Mutations In The PI3K Signalling Pathway
Funder
National Health and Medical Research Council
Funding Amount
$975,476.00
Summary
Activation of immune cells is required to generate appropriate immune responses that protect is from disease caused by pathogens. The inability to receive the correct type of signals causes immunodeficiency. The PI3 kinase pathway is central to immune cell activation – and genetic errors in this pathwat compromise the functioning of immune cells. We will investigate the nature of these defects and pursue avenues of overcoming them using pharmacological inhibitors of the PI3K pathway.
An Exploration Of The Balance Between West Nile Virus Pathogenesis And Immune System Mediated Control
Funder
National Health and Medical Research Council
Funding Amount
$325,442.00
Summary
West Nile Virus (WNV) is a mosquito transmitted infectious disease that is emerging globally. Infection can lead to the development of fatal encephalitis and currently there is no vaccine available for human use. Killer T cells, a component of the immune system, are essential for viral clearance from the brain. This project aims to further explore WNV pathogenesis and whether killer T cells can be utilized to keep the infection localised and prevent the spread of the virus to the brain.
Chronic infectious diseases have a devastating effect on global health. HIV and Plasmodium falciparum both cause chronic disease and have evaded effective vaccine design. Vaccines rely on immune memory – the ability to clear an infection rapidly to a previously encountered pathogen. This proposal investigates the formation and dysfunction of immune memory in chronic infectious diseases, which will be vital for creating new and effective vaccines.
HMGB1: A Novel Player In The Pathogenesis Of Inflammatory Myositis?
Funder
National Health and Medical Research Council
Funding Amount
$84,800.00
Summary
The project aims to determine whether HMGB1, a pro-inflammatory molecule, plays a key role in the cause of inflammatory myositis, an extremely disabling muscle condition characterised by progressive weakness.
Epigenetic Mechanisms That Regulate B Cell Differentiation And Memory B Cell Persistence To Provide Long-term Immune Protection
Funder
National Health and Medical Research Council
Funding Amount
$318,196.00
Summary
Memory immune cells remember antigens that have previously induced an immune response, and the ability of these cells to rapidly clear pathogens has led to successful vaccination programs. This project will study epigenetic changes during the formation of immune memory that results in protection against foreign antigens. Understanding these processes will assist in creating more effective vaccines and treatments for patients with immune disorders.
Defining The Requirements For Effective Immune Responses
Funder
National Health and Medical Research Council
Funding Amount
$714,745.00
Summary
The immune system rapidly responds to infectious pathogens to eradicate such microbes and limit the damage they can inflict upon the host. Individuals with primary immunodeficiencies have defects in the development and/or function of the cells of their immune system and are more susceptible to infectious diseases. This study will investigate such individuals to identify functions for specific genes and immune cells in order to understand the requirements for generating effective immune responses ....The immune system rapidly responds to infectious pathogens to eradicate such microbes and limit the damage they can inflict upon the host. Individuals with primary immunodeficiencies have defects in the development and/or function of the cells of their immune system and are more susceptible to infectious diseases. This study will investigate such individuals to identify functions for specific genes and immune cells in order to understand the requirements for generating effective immune responses.Read moreRead less
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