Autoimmunity In Double Transgenic Models Of Self Tolerance
Funder
National Health and Medical Research Council
Funding Amount
$157,660.00
Summary
The immune system protects the body against infection by means of a population of circulating white blood cells called lymphocytes. Each lymphocyte has on its surface its own particular receptor which recognises only one out of the universe of possible substances. Receptors are generated in a semi-random way, using a combination of elements encoded by the genes, and it is possible to generate receptors that react with the body itself, rather than with invading organisms. If the cells bearing the ....The immune system protects the body against infection by means of a population of circulating white blood cells called lymphocytes. Each lymphocyte has on its surface its own particular receptor which recognises only one out of the universe of possible substances. Receptors are generated in a semi-random way, using a combination of elements encoded by the genes, and it is possible to generate receptors that react with the body itself, rather than with invading organisms. If the cells bearing these self-reactive receptors become activated, an autoimmune disease ensues. We are using animal models to study how the body deals with self-reactive cells. We will attempt to activate these cells and thus cause autoimmune disease. The experimental manoeuvres that successfully cause autoimmunity in normal animals will provide clues as to the processes that can cause autoimmune disease.Read moreRead less
The Role Of Dendritic Cell Subsets In The Decision Between T Cell Tolerance And Immunity
Funder
National Health and Medical Research Council
Funding Amount
$445,009.00
Summary
The immune system protects the body against infection by means of a population of circulating white blood cells called lymphocytes. Each lymphocyte has on its surface its own particular receptor which recognises only one out of the universe of possible substances. Receptors are generated in a semi-random way, using a combination of elements encoded by the genes, and it is possible to generate receptors that react with the body itself, rather than with invading organisms. If the cells bearing the ....The immune system protects the body against infection by means of a population of circulating white blood cells called lymphocytes. Each lymphocyte has on its surface its own particular receptor which recognises only one out of the universe of possible substances. Receptors are generated in a semi-random way, using a combination of elements encoded by the genes, and it is possible to generate receptors that react with the body itself, rather than with invading organisms. If the cells bearing these self-reactive receptors become activated, an autoimmune disease ensues. The question of how lymphocytes can tell the difference between the body itself and foreign organisms is of major interest to immunologists. One of the first ideas was that self-reactive lymphocytes are inactivated by making reactions early in life. Despite the simplicity and intellectual appeal of this idea, it is inconsistent with a large body of experimental evidence. On the basis of number of new experiments, I have proposed an alternative model of self tolerance for one of the subsets of lymphocytes. In this model, the cells that help lymphocytes to recognise particular substances possess the property of distinguishing self from foreign, and pass that information on. The aim of this project is to provide direct experimental evidence in support of the model. Many of our attempts to deal with medical problems related to the immune system have been hampered by our lack of understanding of exactly how immune tolerance is controlled. If my model proves to be correct, it will be possible to manipulate immune responses with far greater effectiveness, providing new treatments for autoimmune disease, allergy, graft rejection and vaccination.Read moreRead less
Immunodominance And Protective Immunity In The Context Of A Complex Host-pathogen System.
Funder
National Health and Medical Research Council
Funding Amount
$899,832.00
Summary
In experimental infection models with simple organisms, pathogen-specific immune responses recognize only a small fraction of potential epitopes encoded by the genome. This phenomenon is termed immunodominance. We propose the first comprehensive study of immunodominance in humans in response to a complex pathogen, the Plasmodium parasite that causes malaria. This will provide valuable new knowledge of host-pathogen immunity and facilitate rational vaccine design.