Dynamic Imaging Of The Immune Response In Lymph Nodes By Two-photon Microscopy
Funder
National Health and Medical Research Council
Funding Amount
$79,514.00
Summary
Despite the enormous contribution of vaccination to the prevention of human disease and suffering, little is known about the laws that govern the selection and survival of B cells during the response to infection or vaccination. Our research projects aim to integrate several cutting-edge technologies, including two-photon microscopy, in order to understand the cellular and molecular basis of immunity.
This Program Grant brings together a world-leading team of experts to elucidate mechanisms that protect most people from infection by making antibodies, and their failure caused by genes or infections like influenza or HIV. The team will determine mechanisms that protect most people from making antibodies against normal parts of our body, whose failure causes numerous autoimmune diseases including rheumatoid arthritis. The team will develop ways to engineer better antibodies.
Epigenetic Mechanisms That Regulate B Cell Differentiation And Memory B Cell Persistence To Provide Long-term Immune Protection
Funder
National Health and Medical Research Council
Funding Amount
$318,196.00
Summary
Memory immune cells remember antigens that have previously induced an immune response, and the ability of these cells to rapidly clear pathogens has led to successful vaccination programs. This project will study epigenetic changes during the formation of immune memory that results in protection against foreign antigens. Understanding these processes will assist in creating more effective vaccines and treatments for patients with immune disorders.
Defining The Stage Specific Requirements For Bcl-2 Family Members In The Development And Maintenance Of B Cell Memory
Funder
National Health and Medical Research Council
Funding Amount
$632,438.00
Summary
Both vaccinations and pathogenic infections provoke an immune response. Our immune system ñmemorizesî this response, enabling a faster and stronger reaction upon re-encounter. This memory requires specialized cells of the immune system, some of which secrete antibodies and some of which patrol the body. Remarkably, these cells can live for decades in humans and provide immunity. In this project we will study the roles of specific proteins regulating the generation and survival of memory cells.
Identification Of Antigen Selection In The Human IgE Response By Analysis Of Somatic Point Mutations
Funder
National Health and Medical Research Council
Funding Amount
$256,973.00
Summary
Allergic disease affects over 25% of the Australian community. It is responsible for significant sickness and death, particularly amongst children, and its incidence is on the increase. The reasons for this, and the underlying causes of allergic disease, remain unclear. Allergic disease results from the actions of molecules called IgE antibodies, which are also associated with parasitic infection. Even in these conditions, where IgE concentrations are raised in the blood, the concentrations are ....Allergic disease affects over 25% of the Australian community. It is responsible for significant sickness and death, particularly amongst children, and its incidence is on the increase. The reasons for this, and the underlying causes of allergic disease, remain unclear. Allergic disease results from the actions of molecules called IgE antibodies, which are also associated with parasitic infection. Even in these conditions, where IgE concentrations are raised in the blood, the concentrations are too low to allow their direct study. We have recently applied molecular biological techniques to study the genes that encode IgE antibodies. Our work suggests that the IgE response can sometimes develop in a different way to that of other antibodies (eg IgG). On the other hand, laboratory (in vitro) studies over many years support the possibility that IgE and IgG develop in parallel. In this study, we wish to identify circumstances in which IgG-like IgE antibodies develop. We therefore wish to study patients with different kinds of allergic disease, and patients with other conditions that are associated with IgE production. We therefore wish to study patients who have infections with parasitic worms. We deduce the processes that give rise to IgE antibodies by analysing patterns of mutations that accumulate in antibody genes during an immune response. Over recent years, we have developed new approaches to the analysis of such mutations, and this project also seeks to further develop our mutation analysis. This more powerful analysis will be applied to the study of mutations in the IgE genes seen in different patient groups, and should allow us to quantify the proportion of IgE antibodies that develop in each way. A better understanding of the relative contributions of the two pathways to IgE, in different conditions, will transform our understanding of the IgE response, and open up new avenues for the investigation of the causes and treatment of allergic disease.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