How Deletional And Non-Deletional Tolerance Mechanisms Integrate To Prevent Autoimmune Disease
Funder
National Health and Medical Research Council
Funding Amount
$509,944.00
Summary
The body produces millions of immune cells every day to fight infection. Some of these immune cells are defective and dangerous because they can cause autoimmune diseases, like Type I diabetes and multiple sclerosis. To defuse this risk, such immune cells are either caused to die or are inactivated to prevent autoimmunity. We propose to investigate how the processes of immune cell death and inactivation work in health and disease so we may harness these mechanisms to cure autoimmunity.
The Role Of The T Cell Protein Tyrosine Phosphatase In Autoimmunity
Funder
National Health and Medical Research Council
Funding Amount
$654,725.00
Summary
Autoimmune diseases such as type 1 diabetes, Crohns disease & rheumatoid arthritis collectively affect ~5% of Australians & are associated with the immune system attacking the body’s organs as if they were a foreign infection. Genetic studies in humans & animal studies point towards the enzyme TCPTP being important in the prevention of autoimmunity. This proposal will define the molecular & cellular pathways by which TCPTP prevents autoimmunity.
Unraveling Mechanisms Of Liver Transplant Tolerance
Funder
National Health and Medical Research Council
Funding Amount
$694,822.00
Summary
Liver transplants are unique amongst solid organs as they are spontaneously accepted across different individuals and induce acceptance of other organs from the same donor co-transplanted at the same time. Using a new mouse liver transplantation model, this proposal will elucidate how the liver tissue performs this function and identify new markers associated with tolerance in the blood of mice. This knowledge will be used to identify liver transplant patients with reduced rejection risk.
Impaired Respiratory Tolerance In Obesity - The Link With Asthma?
Funder
National Health and Medical Research Council
Funding Amount
$667,294.00
Summary
Australia has one of the highest obesity rates in the world, placing a major strain on health budgets. Obesity increases the risk of numerous diseases, including asthma. Asthma is prevented in healthy people by the immune system. This project will investigate whether obesity-related dietary factors and/or gut microbes impair this immune-mediated mechanism. Outcomes will increase understanding of the effects of diet and obesity on asthma development, and lead to novel asthma therapies.
Deciphering How TCR Affinity Regulates CD4 T Cell Help In Immunity And Autoimmunity
Funder
National Health and Medical Research Council
Funding Amount
$850,885.00
Summary
Immune responses require the coordinated interaction and cross-talk between two types of white blood cells known as CD4 and CD8 T cells. A dysregulated interaction between these cells could be the cause of autoimmune and persistent infections by pathogens leading to chronic diseases. The aim of this proposal is to provide a deeper understanding of CD4/CD8 T cell interactions to improve immune outcomes in many chronic diseases in which interaction between these two immune cells is critical.
The Influence Of NF-KB In The Development Of Autoimmunity And Cancer In Fas/FasL Mutant Mice
Funder
National Health and Medical Research Council
Funding Amount
$596,925.00
Summary
Apoptotic cell death is an essential process in the human body, it removes useless and dangerous cells, preventing autoimmune disease and cancer. Apoptosis is activated when the surface receptor Fas is stimulated by its ligand, FasL, but defective signalling causes disease associated with deregulated NF-?B activation. We will investigate how faulty FasL-induced apoptosis cooperates with deregulated NF-kB activation or defective Aire (immunological tolerance orchestrator) results in autoimmunity.
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
The Impact Of Obesity On Immunological Tolerance Of The Fetus
Funder
National Health and Medical Research Council
Funding Amount
$378,366.00
Summary
Obesity increases the risk of miscarriage during pregnancy. The reasons for this are not known, although it is thought that abnormal levels of hormones and metabolic parameters are a contributing factor. We hypothesise that the immune system plays a role. In this project we will determine if obesity upsets the fine-tuning of the immune system that is crucial for successful pregnancy. Understanding the reason behind adverse pregnancy outcome will allow appropriate management of maternal obesity.
Prevention Of Autoimmune Diabetes By Immune Tolerance To Proinsulin
Funder
National Health and Medical Research Council
Funding Amount
$504,597.00
Summary
In type 1 diabetes, insulin is the first target of the immune system. Strategies to prevent the immune system targeting insulin in mice early in the disease process work, but it is not clear if such strategies would be effective if applied late. This is important because preventive therapies for human type 1 diabetes are currently feasible only late in the disease process. We aim to address this by removing T cells specific for insulin at different stages of the disease.
The Male Partner Contribution To Pregnancy Immune Tolerance Deficit In Women
Funder
National Health and Medical Research Council
Funding Amount
$1,462,925.00
Summary
A complication-free pregnancy and birth of a healthy infant depends on adequate preparation of the mother's immune system to tolerate the 'foreign' fetus, Both the mother and the father contribute to establishing optimal immune tolerance. This project will determine the links between specific agents in male seminal fluid and the female immune response, and will make progress towards new diagnostic tests and treatment options for unexplained subfertility and gestational disorders.