Induction Of Natural T-Regulatory Cells By Thymic Dendritic Cell Populations
Funder
National Health and Medical Research Council
Funding Amount
$413,775.00
Summary
In this study, we will determine the roles of the antigen presenting cells, namely denderitic cells, in the induction of T-regulatory cell (T-reg) developemnt in the thymus. T-reg cells play important roles in controlling the development of autoimmunity. This study will help to understand the possible causes of autoimmune diseases and to develop new treatments for these diseases.
Parkinson s disease (PD) is a progressively disabling movement disorder afflicting over 25,000 Australians. It is caused by the degeneration of specific nerve cells in the brain that produce certain chemcials and patients suffer from an inability to move fluently (or ultimately at all). At present we do not know what triggers this neurodegeneration. Current symptomatic treatments give sufferers some relief for a period of time by boosting the amount of these depleted chemicals in the brain. Howe ....Parkinson s disease (PD) is a progressively disabling movement disorder afflicting over 25,000 Australians. It is caused by the degeneration of specific nerve cells in the brain that produce certain chemcials and patients suffer from an inability to move fluently (or ultimately at all). At present we do not know what triggers this neurodegeneration. Current symptomatic treatments give sufferers some relief for a period of time by boosting the amount of these depleted chemicals in the brain. However, the underlying cellular degeneration continues unabated until such treatments are no longer effective. It is necessary to determine the reason for the cell loss in the brain in order to develop successful long-term treatments for this disabling disorder. There have been a number of animal models for PD developed. Comparing the type of tissue damage associated with the cell loss in these models shows that signs of brain inflammation occur prior to the loss of nerve cells. This feature consistently occurs regardless of the method used to produce the disease model. However, inflammation has been poorly studied in PD. Part of the present proposal is to analyse the brain tissue from patients with PD in order to document whether inflammation is also a consistent feature in the regions affected by the disease. Other central nervous system disorders in which inflammation is thought to play a pivotal role often have some genetic predisposition to the disorder and there is evidence of an immune response in their blood. We also wish to examine these aspects in patients with PD. Overall, our study will provide the necessary evidence for or against a primary role for inflammation in the disease process causing the ongoing degeneration in PD. If significant indications for a primary role for inflammation are found, treatments specifically targeting inflammation (already available) can be trialled to slow or stop the neurodegeneration.Read moreRead less
The Differential Contribution Of Programmed Death-1 Ligands To Malarial Immunity
Funder
National Health and Medical Research Council
Funding Amount
$327,784.00
Summary
This research aims to understand how the Malaria parasite, which causes one of the world’s deadliest diseases, evades immunity. It will provide a significant advance in our knowledge of immunity against malaria and impact on current strategies to develop an efficacious vaccine or treatment for malaria.
The Role Of Self Reactive T Cells In The Normal TCR Repertoire
Funder
National Health and Medical Research Council
Funding Amount
$363,601.00
Summary
The immune system is highly regulated and sophisticated in order to distinguish foreign invaders from our own body. Once control is lost in this system, mistakes can happen, and autoimmunity, attack of ones self may result. Surprisingly potentially dangerous ‘fighter’ T cells can be readily found in healthy individuals whom are free from autoimmunity. The aim of this project is to understand how we can survive with these potentially harmful T cells around and what may activate them.
The Appendix In Intestinal Immunity And Inflammatory Bowel Disease
Funder
National Health and Medical Research Council
Funding Amount
$465,210.00
Summary
Inflammatory bowel diseases (IBD) consist of two entities: ulcerative colitis and Crohn's disease. IBD causes relapsing and remitting gut inflammation in relatively young populations of patients. Our understanding of causes of IBD is poor, but the diseases involve an interaction between the intestinal immune system, genetic predisposition and bacteria in the gut. One unexplained observation, made by a number of groups, is that removal of the appendix, especially if performed when young, protects ....Inflammatory bowel diseases (IBD) consist of two entities: ulcerative colitis and Crohn's disease. IBD causes relapsing and remitting gut inflammation in relatively young populations of patients. Our understanding of causes of IBD is poor, but the diseases involve an interaction between the intestinal immune system, genetic predisposition and bacteria in the gut. One unexplained observation, made by a number of groups, is that removal of the appendix, especially if performed when young, protects against the later development of ulcerative colitis and probably Crohn s disease. If IBD does develop following earlier appendicectomy, it tends to be less severe. In this project, we plan to examine the immune features of the appendix, in human and mouse. The appendix is a major source of immune cells in the intestine but the nature of these cells and their functions are poorly understood. The aims of the project will explore the nature of immune cells, known as T lymphocytes, isolated from human and mouse appendices. Changes with age will be examined, to explain the age-related nature of the appendicectomy-IBD link. Anti- and pro-inflammatory characteristics of the cells will be studied, the migration pathways of these cells from appendix to other parts of the intestine will be clarified, and the therapeutic potential of these T cells in a mouse model of IBD will be elucidated. In addition, this will be the first study to develop and analyse a mouse model of appendicitis, which is very poorly understood. These studies will make important observations relevant not only to IBD, but to the immune function of the intestine, with implications for our fundamental understanding of the way we are protected from our hostile environment.Read moreRead less
Regulation Of Immune Mechanisms By Pathogen Cysteine Proteases
Funder
National Health and Medical Research Council
Funding Amount
$424,676.00
Summary
To survive, parasites have evolved many strategies to control the human immune system. We have identified an enzyme secreted by parasites that can manipulate cells of the immune system, subsequently preventing the development of inflammatory responses. We will investigate the mechanism involved and determine whether this enzyme could be exploited for therapeutic purposes to switch off inflammation in autoimmune disease such as type-1 diabetes.
UNDERSTANDING HEPATITIS C VIRUS-SPECIFIC T CELL TOLERANCE
Funder
National Health and Medical Research Council
Funding Amount
$429,710.00
Summary
Most individuals who are infected with hepatitis C virus (HCV) develop a persistent infection that is lifelong and are at risk of developing serious liver disease, including liver cancer. The evidence suggests that an inadequate immune response is responsible for the inability of the patient to resolve the infection, but it is not clear which stage of the immunological cascade might be targeted. In this project, we will test the hypothesis that HCV antigen induce supressor T cells This will have ....Most individuals who are infected with hepatitis C virus (HCV) develop a persistent infection that is lifelong and are at risk of developing serious liver disease, including liver cancer. The evidence suggests that an inadequate immune response is responsible for the inability of the patient to resolve the infection, but it is not clear which stage of the immunological cascade might be targeted. In this project, we will test the hypothesis that HCV antigen induce supressor T cells This will have the effect of inhibiting the immune response and result in the outcome that we currently recognise as persistent HCV infection.Read moreRead less
Understanding The Mechanisms Of Respiratory Viral Infection- And COPD-induced Predisposition To Secondary Bacterial Pneumonia
Funder
National Health and Medical Research Council
Funding Amount
$593,888.00
Summary
Bacterial pneumonia is a major health problem particularly for children and the elderly. Bacteria are resistant to antibiotics and new treatments are urgently required. Viral infection and emphysema lead to increased risk of pneumonia. We will investigate the mechanisms of how viral infections and emphysema lead to pneumonia. We will then use new treatments to stop these mechanisms from occurring to prevent and treat pneumonia. This project may produce new treatments and cures for pneumonia.