Genetic Determinants Of Interleukin-10 Response After Infectious Stimuli
Funder
National Health and Medical Research Council
Funding Amount
$276,000.00
Summary
Interleukin-10 is a key protein in the immune defense against infection, being the principal brake for the immune response. An diminished production of interleukin-10 has been implicated as a major cause of a number of devestating medical conditions including septic shock and acute respiratory distress syndrome. An excessive production of interleukin-10 may also be very harmful, and may be the primary cause of the reduction in immune function in many critically ill patients that leads to hospita ....Interleukin-10 is a key protein in the immune defense against infection, being the principal brake for the immune response. An diminished production of interleukin-10 has been implicated as a major cause of a number of devestating medical conditions including septic shock and acute respiratory distress syndrome. An excessive production of interleukin-10 may also be very harmful, and may be the primary cause of the reduction in immune function in many critically ill patients that leads to hospital acquired infections. These potential key roles of interleukin-10 in seriously ill patients makes it an attractive candidate to target for immune therapies. However, past experience with trials of immune-based therapies such as tumor necrosis factor alpha have taught us that we need to be much better at predicting individual immune responses if we are to 'interfere' with the immune system successfully. In the case of interleukin-10 there is substantial individual variation in the amount produced, with studies suggesting up to 70% of this variation is due to genetic differences. This project will establish the basis for this genetic variation by identiying both the genetic markers of high and low interleukin-10 response and the mechanisms by which these genetic markers change interleukin-10 production. This information will not only enable us to better target patients who may need an 'adjustment' of their immune function, but may also lead to novel therapeutic targets or therapeutic agents.Read moreRead less
Cutaneous Inflammation, Bone Marrow Dendritic Cells, And Implications For Immune Responses And Immune Homeostasis
Funder
National Health and Medical Research Council
Funding Amount
$327,151.00
Summary
With inflammation of the skin due to excessive sun exposure or chemicals, biological signals are sent to the bone marrow where immune fighting cells are generated. However, the immune system must not overreact. We have measured bone marrow derived immune cells with reduced function following skin inflammation which we propose is part of homeostasis. We need to better understand how these cells are altered and for how long they are altered.
Cytokines Regulating Airway Inflammation, Remodelling And Hyper-reactivity In Chronic Asthma
Funder
National Health and Medical Research Council
Funding Amount
$329,500.00
Summary
This project examines a new approach to treatment of asthma, based on immunisation against the body's own chemical signals. The investigators will also be continuing studies on how twitchy airways develop in asthma, the mechanisms by which scarring of the airway walls progresses, and the signals that trigger inflammation of the airways. These studies will use a much-improved mouse model of the disease. In this experimental model, which was developed by the investigators, sensitised mice are chro ....This project examines a new approach to treatment of asthma, based on immunisation against the body's own chemical signals. The investigators will also be continuing studies on how twitchy airways develop in asthma, the mechanisms by which scarring of the airway walls progresses, and the signals that trigger inflammation of the airways. These studies will use a much-improved mouse model of the disease. In this experimental model, which was developed by the investigators, sensitised mice are chronically exposed to low concentrations of aerosolised egg white protein. The proposed studies will involve comparisons with animals that are immunised against certain inflammation-related molecules, as well as with mice that are genetically deficient in their ability to produce such molecules. The results of these studies may help in the development of methods for long-term suppression of the changes that develop in the airways of asthmatics.Read moreRead less
Post-translational Control Of Indoleamine 2,3-dioxygenase
Funder
National Health and Medical Research Council
Funding Amount
$511,294.00
Summary
It is apparent that a protein called indoleamine 2,3-dioxygenase is important for controlling the immune system of relevance to various normal and disease conditions including pregnancy, cancer, inflammation, infectious disease and autoimmunity. Despite this little is known about how this important protein is controlled. The aim of this project is to better understand how this protein is regulated that can highlight ways in which to alter the enzymes activity to modulate immune responces.
A Dendritic Cell Subset Targeting Approach For Generating Humoral Immunity
Funder
National Health and Medical Research Council
Funding Amount
$678,492.00
Summary
Potent vaccination might be achieved by using monoclonal antibodies as magic bullets to target vaccines to special cells in the body. We show that targeting these special cells by using monoclonal antibodies that recognise Clec9A is effective, perhaps because it brings several different immune cells together so that they orchestrate very efficient immune responses. This application investigates how targeting Clec9A allows strong vaccination so that we can apply this to new generation vaccines.
A Dendritic Cell Subset Targeting Approach For Defining Immune Function And Tailoring Immunotherapy
Funder
National Health and Medical Research Council
Funding Amount
$692,753.00
Summary
Dendritic cells are important sentinel cells of the immune system that orchestrate our immune responses against invading pathogens. There are different types of dendritic cells and they perform different jobs. We have a series of antibodies that can recognise markers on the surface of different dendritic cells populations. We can use these antibodies as homing devices to deliver foreign material to individual dendritic cell subpopulations and thereby manipulate the type of immune response genera ....Dendritic cells are important sentinel cells of the immune system that orchestrate our immune responses against invading pathogens. There are different types of dendritic cells and they perform different jobs. We have a series of antibodies that can recognise markers on the surface of different dendritic cells populations. We can use these antibodies as homing devices to deliver foreign material to individual dendritic cell subpopulations and thereby manipulate the type of immune response generated. Effectively, we aim to tailor immune responses to fight a particular bacteria, virus, parasite, or even cancer cells. The current proposal will extend the number of antibodies we test for their ability to generate tailored immunity. We will examine a number of new molecules for their ability to shuttle foreign material to dendritic cells and their ability to stimulate immune responses. Next, we will test these homing devices as vaccines and their ability to prevent or treat cancer. Our aim is to develop a robust, highly efficient, generic, vaccination approach for cancer immunotherapy.Read moreRead less