Transcriptional Regulation Of Terminal T Cell Differentiation By Blimp-1
Funder
National Health and Medical Research Council
Funding Amount
$411,404.00
Summary
Memory cells stand at the end of immune reactions and determine the success or failure of vaccination. T cells in are considered essential in tumour surveillance, clearance of infections and in providing help for antibody decretion. Blimp-1 is a major factor controling the differentiation of effector T cells. We aim to study its role in the generation of memory T cells which will help to develop better stratagies for immunization and for the treatment of immunodedeficiency and autoimmunity.
The Ontogeny Of TLR Mediated Innate Immune Function In Normal And Atopic Children
Funder
National Health and Medical Research Council
Funding Amount
$463,328.00
Summary
Bacteria are first recognised by the immune system though primitive innate immune pathways which are highly conserved through evolution. The activation of these pathways is critical for the maturation of the immune system. This may explain the rise in immune diseases with cleaner environments (and less innate immune activation). We speculate that functional differences (as a result of environmental or genetic factors) are implicated in the rising rates of allergic disease. This is the first stud ....Bacteria are first recognised by the immune system though primitive innate immune pathways which are highly conserved through evolution. The activation of these pathways is critical for the maturation of the immune system. This may explain the rise in immune diseases with cleaner environments (and less innate immune activation). We speculate that functional differences (as a result of environmental or genetic factors) are implicated in the rising rates of allergic disease. This is the first study to document normal maturation of these innate pathways in early childhood, and to compare this in allergic and nonallergic children. We will do this using existing samples collected as part of previous cohort studies. This study is the logical next step in the quest to define allergy pathogenesis. Whatever the outcome, the findings will be of enormous significance. A better understanding of the development of these pathways is also likely to contribute to more avenues for better-targeted treatment and prevention.Read moreRead less
T cells are a central component of the immune system and without T cells the body is very vulnerable to infections. One subgroup of T cells is the killer T cells that are important for identifying and killing cells infected by viruses and bacteria. The immune system works to maintain T cell numbers at a fairly constant level and part of this process includes sending signals to the killer T cells from other cells via cell surface protein interactions and soluble mediators, such as cytokines. We h ....T cells are a central component of the immune system and without T cells the body is very vulnerable to infections. One subgroup of T cells is the killer T cells that are important for identifying and killing cells infected by viruses and bacteria. The immune system works to maintain T cell numbers at a fairly constant level and part of this process includes sending signals to the killer T cells from other cells via cell surface protein interactions and soluble mediators, such as cytokines. We have been studying killer T cells, which are missing a protein SOCS1. SOCS1 is important for switching off the signals generated by a group of cytokines. As a consequence of being unable to correctly regulate cytokine signals these killer T cells multiply inappropriately and contribute to disease development. Our current work is aimed at achieving a better understanding of the particular interactions between killer T cells and other immune system cells and the soluble factors that deliver important signals for maintaining killer T cells in the immune system. The ability to better understand the factors controlling the maintenance of killer T cells will enable us to more intelligently target the immune system ,which is important for improving vaccine strategies and cancer immunotherapy as well as for controlling T cells that are activated inappropriately, such as in autoimmune disease.Read moreRead less
Transcriptional Regulation Of T Cell Memory Programming
Funder
National Health and Medical Research Council
Funding Amount
$549,092.00
Summary
Differentiation of T cells is required to protect against disease. A group of proteins, called transcription factors, critically regulate this fundamental process, during which T cells become effector cells (that can kill pathogen infected cells) or memory cells (that are essential for protection against secondary infections). To identify the functions and hierarchy of these regulators is critical to therapeutic treatment of autoimmune and infectious disease and is the aim of this application.
CD4 T-cell Deficiency And Dysfunction In HIV Patients Receiving Effective Antiretroviral Therapy
Funder
National Health and Medical Research Council
Funding Amount
$490,020.00
Summary
Large numbers of people throughout the world will commence antiretroviral treatment for HIV infection over the next 5 years. This treatment partially corrects CD4 T-cell deficiency (the most characteristic immune defect caused by HIV infection) but does not restore the immune system to normal in patients who were very immunodeficient before treatment. This study will determine the cause of residual immune defects in patients receiving antiretroviral drugs with the aim of introducing new therapie ....Large numbers of people throughout the world will commence antiretroviral treatment for HIV infection over the next 5 years. This treatment partially corrects CD4 T-cell deficiency (the most characteristic immune defect caused by HIV infection) but does not restore the immune system to normal in patients who were very immunodeficient before treatment. This study will determine the cause of residual immune defects in patients receiving antiretroviral drugs with the aim of introducing new therapies to correct those defects. Our previous studies have demonstrated that the production of new T-cells in HIV patients receiving antiretroviral durgs is affected by the function of the thymus, but that this does not account for the production of all new T-cells. We will investigate other sites of T-cell production in the body. We have also previously shown that poor recovery of CD4 T-cells in patients successfully treated with antiretroviral drugs is associated with immune activation and that the T-cells do not function adequately, even when CD4 T-cell counts are substantially increased. We will determine whether these abnormalities are the result of a persistent defect in T cell activation by monocytes and-or dendritic cells. The findings of our studies will improve the treatment and life-expectancy of individuals with HIV infection.Read moreRead less
Autoimmune diseases constitute a significant medical problem in the developed world and are increasing in incidence. Many control mechanisms exist in the body, but in people with genetic susceptibility to autoimmune disease, the mechanisms fail and the body's immune system attacks normal tissues or organs. We have developed a new approach, using the cells which train the immune system, to re-educate the cells that would otherwise attack normal healthy tissues in autoimmune-prone individuals. The ....Autoimmune diseases constitute a significant medical problem in the developed world and are increasing in incidence. Many control mechanisms exist in the body, but in people with genetic susceptibility to autoimmune disease, the mechanisms fail and the body's immune system attacks normal tissues or organs. We have developed a new approach, using the cells which train the immune system, to re-educate the cells that would otherwise attack normal healthy tissues in autoimmune-prone individuals. These cells (dendritic cells) are genetically modified to express the molecular targets of the autoimmune response. This in turn switches off the response to these targets. In this project, we will explore how these cells can be used to turn off the harmful cells present in the immune system.Read moreRead less
Regulating The Production Of High Affinity Antibody Forming Cells During The Germinal Centre Reaction.
Funder
National Health and Medical Research Council
Funding Amount
$376,980.00
Summary
In response to infection the body makes antibodies. These antibodies are important in helping clear the infection and keeping us healthy. What's more, the immune system 'remembers' these past infections. This means that when we are re-exposed to an infectious agent like measles virus, no disease develops. This is because the antibodies which cleared the infection initially, are still being made and prevent or neutralize the new infection or toxin. The continued production of these antibodies is ....In response to infection the body makes antibodies. These antibodies are important in helping clear the infection and keeping us healthy. What's more, the immune system 'remembers' these past infections. This means that when we are re-exposed to an infectious agent like measles virus, no disease develops. This is because the antibodies which cleared the infection initially, are still being made and prevent or neutralize the new infection or toxin. The continued production of these antibodies is therefore an important part of staying healthy. When we are vaccinated, we produce antibodies specific for the components of the vaccine. Some of these components are part of the real infectious agent. This means that when we encounter the real virus, we already have antibodies that prevent the virus from doing any damage. Booster immunizations are necessary to make sure we have high enough levels of these neutralizing antibodies. Being able to understand how these important antibodies are made is a central goal of this research project. We hope that by understanding how cells are durected in an immune response to become the kind of cells that secretes neutralizing antibodies, we will be able to make vaccines that work more efficiently, that require fewer booster injections and that give longer lasting protection. We also hope that we can better design vaccines so that those that currently don't work, can be made to do so.Read moreRead less
Transcriptional Regulation Of T Lymphocyte And Dendritic Cell Development
Funder
National Health and Medical Research Council
Funding Amount
$605,096.00
Summary
Differentation of lymphocytes is a fundamental process in protection against disease . A small number of proteins critically regulate the decisions the cells make in becoming effective antigen presenting cells (that stimulate other immune cells), effector cells (that kill pathogen infected cells) or memory cells (that are essential for protection against secondary infections). Understanding this process and its regulation is critical to therapeutic treatment of autoimmune and infectious disease.
The Regulation And Differentiation Potential Of Human Memory B Lymphocytes
Funder
National Health and Medical Research Council
Funding Amount
$227,036.00
Summary
Antibody produced by our immune system plays a critical role in protecting us from infectious disease. Remarkably our ability to make antibodies is much faster the second time we see the infection. This memory of the previous attack occurs due to the formation of memory B cells that circulate in the blood, sometimes for years, looking for the same intruders. If they detect the infection they rapidly become activated and remake the antibody. These memory cells are very important for our protectio ....Antibody produced by our immune system plays a critical role in protecting us from infectious disease. Remarkably our ability to make antibodies is much faster the second time we see the infection. This memory of the previous attack occurs due to the formation of memory B cells that circulate in the blood, sometimes for years, looking for the same intruders. If they detect the infection they rapidly become activated and remake the antibody. These memory cells are very important for our protection. Vaccines operate by tricking the immune system into making these memory cells, even though the body hasn't seen the actual disease. Although clearly vital for our health little is known about the activation and antibody production by human B memory cells. This project will redress our lack of knowledge by performing a comprehensive evaluation of the properties of this important cell type.Read moreRead less
Immune reactions are mediated by the expansion of white blood cells, and the progeny of this expansion is steered down different developmental pathways depending upon the nature of the initial infection or insult. We have recently identified a new means for control of the developmentwhite blood cells, and will here define this mechanism. These studies will open new opportunities for autoimmune therapeutics and vaccine development.