A Congenic Approach To Analysing The Genomic Control Of Innate Immunity In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$240,156.00
Summary
In addition to the lymphocytes, which are specialised white cells that can learn to defeat the infections that the body has been previously exposed, the body has a number of other defences. These non-learning systems have been honed by evolution and usually form an effective first-line of defence. This proposal deals with three: complement, and two highly specialised types of white blood cell, the Natural Killer cells and the NKT cells. The project will study mice especially bred to carry differ ....In addition to the lymphocytes, which are specialised white cells that can learn to defeat the infections that the body has been previously exposed, the body has a number of other defences. These non-learning systems have been honed by evolution and usually form an effective first-line of defence. This proposal deals with three: complement, and two highly specialised types of white blood cell, the Natural Killer cells and the NKT cells. The project will study mice especially bred to carry different versions of the genes which control these defences. Particular attention will be paid to their involvement in the autoimmune diseases, type 1 diabetes and lupus.Read moreRead less
Functional Genomic Analysis Of NK And NKT Cell Immune Control Of Autoimmunity
Funder
National Health and Medical Research Council
Funding Amount
$692,040.00
Summary
The major populations of white blood cells responsible for learned immunity to are the B cells, which make antibody against microorganisms like bacteria, and the T cells, which kill virally infected cells and help B cells produce antibody. The T and B cells occasionally attack the body s own tissues, resulting in autoimmune disease. These diseases include type 1 diabetes, lupus, and anaemia, and collectively represent the third commonest cause of morbidity and mortality in humans. The major reas ....The major populations of white blood cells responsible for learned immunity to are the B cells, which make antibody against microorganisms like bacteria, and the T cells, which kill virally infected cells and help B cells produce antibody. The T and B cells occasionally attack the body s own tissues, resulting in autoimmune disease. These diseases include type 1 diabetes, lupus, and anaemia, and collectively represent the third commonest cause of morbidity and mortality in humans. The major reason why autoimmunity occurs is thought to be due to a failure in the mechanisms responsible for controlling such unwanted responses. Two other populations of white blood cells are involved in this regulation, termed NK and NKT cells, each of which release important cell hormones. The current project is designed to test whether defects in NK and NKT cells lead to autoimmune disease. For this purpose a special strain of mice (NOD mice) will be used. The reasons for their selection are: 1) they are highly susceptible to a range of autoimmune diseases including diabetes, lupus and anaemia, and 2) we and others have found that they are deficient in both NK and NKT cells. The proposed experiments are divided into two groups, one designed to characterise the nature of the defects in these cells and the other to identify the genes responsible for them. In this way it should be possible to shed light on the genetic basis of autoimmune diseases in general. The approach to be used involves sophisticated techniques of genetic analysis, which require production of special congenic lines of mice. These mice are like NOD mice but carry in addition to NOD genes genetic regions from a non-autoimmune strain with the potential to correct the defects in NK and NKT cells. In this way, it should be possible to pinpoint the disease susceptibility genes involved in causation of autoimmunity and to work out how they affect NK and NKT cells.Read moreRead less
Allogeneic stem cell transplantation (SCT) remains the most effect curative treatment for patients with a number of malignant conditions, especially leukemia. The ability to cure leukemia by this procedure relates to a process known as Graft-versus-Leukaemia effects (GVL) which ocurrs when the newly transplanted stem cells (which includes the immune system) recognises the leukemia as foreign and mounts an immune attack against it. These studies will focus on the effect of a cellular pathway invi ....Allogeneic stem cell transplantation (SCT) remains the most effect curative treatment for patients with a number of malignant conditions, especially leukemia. The ability to cure leukemia by this procedure relates to a process known as Graft-versus-Leukaemia effects (GVL) which ocurrs when the newly transplanted stem cells (which includes the immune system) recognises the leukemia as foreign and mounts an immune attack against it. These studies will focus on the effect of a cellular pathway invilving NKT cells that preliminary data suggests is critical to the development of GVL. Methods to augment this activation pathway will be studied in preclinical models that may then be studied in clinical trials with the aim of improving the outcome of patients transplanted for leukemias.Read moreRead less