Mechanisms Controlling Antibody Production By Modulating B Cell Antigen Receptor Signalling
Funder
National Health and Medical Research Council
Funding Amount
$452,125.00
Summary
This project will analyse mechanisms that regulate antibody production in health and disease. In health, antibodies are normally made exclusively against infectious agents, providing long-lasting immunity. Unknown errors in the control of antibody production result in autoimmune diseases such as systemic lupus or rheumatoid arthritis, where antibodies are made against parts of our own bodies, or result in allergies where antibodies are made against innocuous elements of our environment. In order ....This project will analyse mechanisms that regulate antibody production in health and disease. In health, antibodies are normally made exclusively against infectious agents, providing long-lasting immunity. Unknown errors in the control of antibody production result in autoimmune diseases such as systemic lupus or rheumatoid arthritis, where antibodies are made against parts of our own bodies, or result in allergies where antibodies are made against innocuous elements of our environment. In order to develop rational, specific methods for treating these diseases, it is necessary to identify and understand the biochemical mechanisms that normally control antibody formation against infectious agents, self components, and innocuous environmental agents. The project focuses on defining the biochemical mechanisms by which the antibody-forming cells, B lymphocytes, sense infectious, innocuous, or self components. These cells carry specific receptors that bind these components and transmit signals into the B lymphocyte. The research will determine how different types of signal are transmitted by the receptor so that, normally, large amounts of antibody are made against infectious agents but very little antibody is made against self components. By identifying how the types of signals are changed, the results of this project will reveal control mechanisms that may be altered in autoimmunity, allergy or immune deficiency, and that may be able to be used as drug targets to prevent unwanted antibody production to cure these diseases.Read moreRead less
Molecular Dissection Of Cytokine-mediated Regulation Of Human B-cell Differentiation.
Funder
National Health and Medical Research Council
Funding Amount
$119,314.00
Summary
Interleukin 21 is a molecule which activates B cells. Defects in this pathway cause immunodeficiency where individuals cannot make antibodies, while constant activation has been reported in mouse models of autoimmunity. Examining these pathways will shed light on the causes of human immune disease, and may reveal molecules that could be targeted for the treatment of immunodeficiency and autoimmunity. Amplification of normal immune responses could lead to the development of improved vaccines.
Production Of Human Monoclonal Antibodies In Vitro
Funder
National Health and Medical Research Council
Funding Amount
$358,500.00
Summary
Antibodies are defence molecules that permeate our tissues. The diversity of antibodies in a healthy organism is vast, providing the potential to neutralise almost any biological molecule or pathogen with exquisite selectivity. We have invented a cell culture-based platform to generate and select human antibodies specific for any desired target. Unlike most antibodies currently used in laboratories, these antibodies will be usable as drugs as well as for detection of disease.
The Effect Of Follicular Helper T Cells (TFH) On AID Regulation And Selection Of High Affinity Germinal Centre B Cells.
Funder
National Health and Medical Research Council
Funding Amount
$430,964.00
Summary
An integral component of an immune response to foreign pathogens is the production of antibodies by B cells. However, if antibodies react to self-antigens (human molecules rather than bacteria or viruses) they may also cause autoimmune diseases such as lupus. This research project is investigating the mechanisms that control antibody generation by B cells, and how these are dysregulated in autoimmune diseases, such as lupus.
Role Of Complement Factor H And Related Proteins In Regulating Complement Activation And Microbial Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$377,036.00
Summary
A group of proteins in blood called Complement are activated in the presence of foreign cells or organisms and this generally results in their destruction. It is important to direct this destructive activity against foreign and not self tissue. This is achieved by a further family of proteins, including factor H, which regulate complement activity and how these proteins work is the principal focus of this project. There are many diseases in which damage results from inadvertent complement damage ....A group of proteins in blood called Complement are activated in the presence of foreign cells or organisms and this generally results in their destruction. It is important to direct this destructive activity against foreign and not self tissue. This is achieved by a further family of proteins, including factor H, which regulate complement activity and how these proteins work is the principal focus of this project. There are many diseases in which damage results from inadvertent complement damage and the regulatory proteins have therapeutic potential in this area. In addition many bacteria and other microorganisms, which should be destroyed by complement, escape by binding regulatory proteins. Understanding how this is achieved may reveal new targets for vaccine development. Knowledge of how the production of factor H and related proteins will help understand how inflammation occurs and how it might be controlled.Read moreRead less
Monoclonal Antibodies Targeting Plasma Cells As Novel Therapeutic Agents And Diagnostic Tools
Funder
National Health and Medical Research Council
Funding Amount
$199,275.00
Summary
We have a new tool to identify a very rare immune cell type. This cell makes antibodies, powerful and exquisitely specific proteins that fight infection. In health, antibody-producing cells are beneficial, but in disease (rheumatoid arthritis, lupus and myeloma), these cells cause disease or death. Antibody-producing cells are long-lived. We have no means to specifically deplete them. We are developing reagents to identify and deplete antibody-producing cells to use as novel therapeutic agents.
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
Antibodies are made by B-cells and are essential for a functional immune system. B cells circulate in the body, and, when they encounter an invader, they mature into antibody-producing cells (ASC). A small proportion of the cells become “memory” cells with the potential to become ASC should the same infection occur in the future. This is the basis of vaccination. This program aims to understand how a B cell changes into an ASC. We aim eventually to be able to improve vaccines and understand dise ....Antibodies are made by B-cells and are essential for a functional immune system. B cells circulate in the body, and, when they encounter an invader, they mature into antibody-producing cells (ASC). A small proportion of the cells become “memory” cells with the potential to become ASC should the same infection occur in the future. This is the basis of vaccination. This program aims to understand how a B cell changes into an ASC. We aim eventually to be able to improve vaccines and understand diseases such as allergy, lupus, arthritis and leukaemia to develop novel therapies.Read moreRead less
Structure And Function Of Receptors For IgG (FcgammaR)
Funder
National Health and Medical Research Council
Funding Amount
$772,315.00
Summary
We are investigating one of the most important receptor families of inflammatory white blood cells - so called Fc receptors. These are critically important in resistance to infection. Unfortunately they are also crucial in tissue destruction in autoimmune diseases such as rheumatoid arthritis. We will determine how these receptors trigger inflammation and use this information for the development of new drugs to treat rheumatoid arthritis and lupus.
Structure And Function Of Receptors For IgG (FcgammaR)
Funder
National Health and Medical Research Council
Funding Amount
$905,280.00
Summary
This reasearch project is attempting to understand one of the most important mechanisms of resistance to infectious disease and one of the most important mechanisms of induction of destructive inflammation in autoimmune disease. These studies will define how blood proteins called antibodies, antibodies bind to the surface of white blood cells via proteins called Fc receptors that activate these white blood cells. Under normal circumstances this system provides resistance to infection but is invo ....This reasearch project is attempting to understand one of the most important mechanisms of resistance to infectious disease and one of the most important mechanisms of induction of destructive inflammation in autoimmune disease. These studies will define how blood proteins called antibodies, antibodies bind to the surface of white blood cells via proteins called Fc receptors that activate these white blood cells. Under normal circumstances this system provides resistance to infection but is involved in some of the most debilitating diseases, including allergies, bleeding disorders called thrombocytopoenias, inflammation of blood vessels, vasculitis, as well as aspects of rheumatoid arthritis. The successful conclusion of this project will result in knowledge that will enable the development of more effective and highly specific therapeutic approaches to the treatment of disease and a better understanding of the functioning of the immune system.Read moreRead less