Control and effective treatment of autoimmune diseases remain major challenges to our health system. Diseases such as multiple sclerosis, systemic lupus erythematosus, diabetes and pernicious anaemia are serious conditions that are essentially incurable. Current treatment is only effective in providing temporary relief as it is not directed against the underlying disease process. This project will manipulate the immune system in such a way that early disease processes in autoimmunity will be blo ....Control and effective treatment of autoimmune diseases remain major challenges to our health system. Diseases such as multiple sclerosis, systemic lupus erythematosus, diabetes and pernicious anaemia are serious conditions that are essentially incurable. Current treatment is only effective in providing temporary relief as it is not directed against the underlying disease process. This project will manipulate the immune system in such a way that early disease processes in autoimmunity will be blocked with the ultimate goal to cure the disease. Using an experimental model of pernicious anaemia in mice, where the basic pathology is immune-mediated gastritis, the disease will be treated by presenting the disease causing autoantigen via modified, or immature, antigen presenting cells to the immune system. In other experimental models which form the background to this project we have shown that this approach leads to down-regulation of the immune response by generating cells which specifically suppress the immune system. In our studies of autoimmune gastritis we will obtain modified antigen presenting cells from the skin, the blood, the spleen and thymus and use these cells to define optimal conditions for presenting the auto-antigen molecules to achieve the ultimate goal, which is antigen specific suppression of autoimmune gastritis. Our hypothesis is that immature antigen presenting cells are unable to present antigen to induce an effective immune response, but instead induce a response that results in antigen specific suppression. We intend to use this antigen specific suppression to prevent the establishment of autoimmune gastritis as well as treatment of established disease. This is a unique and potentially valuable strategy to treat autoimmune gastritis and offers the potential to apply this approach to other autoimmune conditionsRead moreRead less
Autoimmune diseases are those caused by the body's immune system attacking the body's own tissues. One group of autoimmune diseases, termed the thyrogastric cluster appear to share genetic risk factors, because they tend to occur together - either in the same patient, or else in families. Some of the diseases within the thyrogastric cluster are known to be very complex genetically, while others appear to be much less complex. Furthermore, some animal models of autoimmune diease are genetically s ....Autoimmune diseases are those caused by the body's immune system attacking the body's own tissues. One group of autoimmune diseases, termed the thyrogastric cluster appear to share genetic risk factors, because they tend to occur together - either in the same patient, or else in families. Some of the diseases within the thyrogastric cluster are known to be very complex genetically, while others appear to be much less complex. Furthermore, some animal models of autoimmune diease are genetically simpler still. We have chosen to study the genetics of gastritis in mice that have had their thymuses removed on the third day of life, because this model has relatively few genes involved; we have found that only 4 genes affect the risk of disease. This means that it will give us the optimum chance of identfiying at least one of these genes. The methods used involve both selective breeding techniques and generating special gene transfer mice in which individuals from one strain will carry the inserted genes from another. In this way, we can identify exactly which genes affect the risk of disease. Once identified, the gene sequences will help us determine if the same gene plays a role in human disease, and if so, to develop new diagnostic tests and therapies.Read moreRead less
A Functional Genomic Approach To The Genetics Of Autoimmune (type A) Gastritis
Funder
National Health and Medical Research Council
Funding Amount
$467,640.00
Summary
The thymus produces white blood cells which defend the body from infections and cancer. Unfortunately, these white blood cells can also cause disease if they target the body's own tissues. These disesaes are called autoimmune diseases, and an example of such a disease is autoimmune (type A) gastritis, in which the white cells target the acid-producing cells of the stomach. The resulting damage can lead to the development of pernicious anaemia (vitamin B12 deficiency) and cancer of the stomach. T ....The thymus produces white blood cells which defend the body from infections and cancer. Unfortunately, these white blood cells can also cause disease if they target the body's own tissues. These disesaes are called autoimmune diseases, and an example of such a disease is autoimmune (type A) gastritis, in which the white cells target the acid-producing cells of the stomach. The resulting damage can lead to the development of pernicious anaemia (vitamin B12 deficiency) and cancer of the stomach. This project studies a mouse model of autoimmune gastritis with the aim of identifying the genes that encode susceptibility to the disease in this model. Ultimately, this information should help us to devise therapies that can be applied to the clinical situation. We have previously identified the locations of the genes which are responsible for causing gastritis in these mice. Two of them are very close together on one chromosome and appear to be very important because they have the strongest effects. Furthermore, there is some evidence that these genes may also be involved in determining susceptibility to diabetes and lupus. This project aims to further characterise these genes by locating them more exactly and by examining their effect on mice not normally prone to gastritis.Read moreRead less
The Generation And Function Of Tissue-specific Regulatory T Cells
Funder
National Health and Medical Research Council
Funding Amount
$488,577.00
Summary
The immune system normally protects against invasion by pathogens such as harmful viruses and bacteria. In autoimmune diseases the same mechanisms that are used to protect us are erroneously targeted to our own tissues. We will discover how regulatory lymphocytes, are able to protect against autoimmune disease. Such regulatory lymphocytes are attractive therapeutic agents to prevent a variety of immune-mediated diseases, including autoimmune diseases, allergy and transplantation rejection.
Vaccinating Against Helicobacter Pylori-induced Gastric Cancer
Funder
National Health and Medical Research Council
Funding Amount
$1,088,714.00
Summary
Stomach cancer is the 3rd leading cause of cancer-related deaths. Most stomach cancers result from inflammation due to Helicobacter pylori infection. Most infections are treatable with antibiotics but this does not protect against cancers that develop before infection is diagnosed. Normal vaccine approaches aimed at this infection have been unsuccessful. We have identified a new approach for protecting against stomach cancer by preventing inflammation; this project aims to develop this vaccine.
Construction And Immunogenic Evaluation Of Recombinant HBsAg-S Virus-like Particles Containing B And T Cell Epitopes Of
Funder
National Health and Medical Research Council
Funding Amount
$170,000.00
Summary
Helicobacter pylori is a significant human pathogen impacting on the health and well being of not only thousands of Australians, but also millions of people world-wide. However, the task of developing a vaccine against H. pylori remains important. Vaccination is the most effective mechanism to prevent disease associated with this infection, particularly gastric cancer, one of the most common causes of cancer death world-wide. However, current attempts to develop an effective vaccine for humans h ....Helicobacter pylori is a significant human pathogen impacting on the health and well being of not only thousands of Australians, but also millions of people world-wide. However, the task of developing a vaccine against H. pylori remains important. Vaccination is the most effective mechanism to prevent disease associated with this infection, particularly gastric cancer, one of the most common causes of cancer death world-wide. However, current attempts to develop an effective vaccine for humans has been limited by the non-availability of an effective and safe adjuvant. The aim is to construct a recombinant Virus-Like Particle which can be used as a safe and effective vaccine against Helicobacter pylori infections. We specifically aim to: · determine the most efficacious singular or combinatorial route-s of delivery of Virus-Like Particles (VLPs) which will induce the desired Th2 and B cell responses in mice · define the Th2 and B cell epitopes of H.pylori Kat A carboxyl terminus that can be used to construct chimeric HBsAg-S-Kat A VLPs · determine if the induction of desired immunological responses in mice are protective against wild type challengeRead moreRead less