B-1 B Cells As A Source Of Polyreactive IgE Antibodies, In Allergic Individuals
Funder
National Health and Medical Research Council
Funding Amount
$331,320.00
Summary
Allergic disease results from the actions of antibody molecules that are produced by cells called B cells. Over the last fifteen years, it has been realised that there are at least two B cell subsets, called B-1 and B-2 cells. The B-1 cells and their antibody products have many unusual features, and they have been implicated in some disease processes. We have recently completed studies that strongly suggest that B-1 B cells may play an important role in some allergic disease. We wish to compare ....Allergic disease results from the actions of antibody molecules that are produced by cells called B cells. Over the last fifteen years, it has been realised that there are at least two B cell subsets, called B-1 and B-2 cells. The B-1 cells and their antibody products have many unusual features, and they have been implicated in some disease processes. We have recently completed studies that strongly suggest that B-1 B cells may play an important role in some allergic disease. We wish to compare groups of patients defined according to their allergic conditions and age, to see whether B-1 B cell activity is associated with particular allergic diseases. We hypothesise that patients with allergic skin conditions have raised numbers of allergy-inducing B-1 cells. Such patients will be compared with those with allergies to inhalent allergens and others with food allergies. Studies will be performed in adult groups as well as in children, for B-1 B cell numbers are known to vary with age. As most of our understanding of the regulation of B cell function, in the context of allergic disease, has arisen from studies conducted with conventional B-2 cells, we also wish to reconsider aspects of B cell regulation. We are specifically interested in the regulation of the 'switching' of B-1 B cells, when they change from the production of antibodies of a 'non-allergic' type (IgM antibodies) to allergy-promoting IgE antibodies. We wish to determine whether the B-1 B cells of allergic individuals are particularly susceptible to such switching, when under the influence of regulatory molecules called cytokines. We expect that B-1 B cells will be associated with some, though not all allergic conditions, and that these cells will emerge as a new target for therapies. Such a finding would be most important. The development of new therapies will require a better understanding of the regulation of these cells, and this will be another important outcome of this project.Read moreRead less
Molecular Mechanisms In The Regulation Of Allergy And Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$4,977,215.00
Summary
To understand the fundamental cellular and molecular processes that underpin the development of allergic disorders, viral infections of the respiratory tract and chronic inflammatory diseases of the lung. There is particular interest in the role of immune cells, such T cells and granulocytes in these disorders, and in the processes that control their function. Understanding these processes will provide new insights into the immune system's role in health and disease, and help develop better ther ....To understand the fundamental cellular and molecular processes that underpin the development of allergic disorders, viral infections of the respiratory tract and chronic inflammatory diseases of the lung. There is particular interest in the role of immune cells, such T cells and granulocytes in these disorders, and in the processes that control their function. Understanding these processes will provide new insights into the immune system's role in health and disease, and help develop better therapies to treat inflammatory disorders.Read moreRead less
Couch Grass Allergy: Cellular And Molecular Studies Directed At Improved Specific Immunotherapy
Funder
National Health and Medical Research Council
Funding Amount
$406,980.00
Summary
Couch grass pollen is increasingly important in Australia and other temperate and subtropical regions as a seasonal allergen causing asthma and hay fever. In our allergy clinic 85% of patients with seasonal asthma and-or hay fever are allergic to both couch grass pollen and rye grass pollen. Standard allergy treatment shots usually cover the rye grass pollen allergens but there is no cross-reactivity with couch grass pollen and therefore symptoms due to couch grass pollen are not controlled. The ....Couch grass pollen is increasingly important in Australia and other temperate and subtropical regions as a seasonal allergen causing asthma and hay fever. In our allergy clinic 85% of patients with seasonal asthma and-or hay fever are allergic to both couch grass pollen and rye grass pollen. Standard allergy treatment shots usually cover the rye grass pollen allergens but there is no cross-reactivity with couch grass pollen and therefore symptoms due to couch grass pollen are not controlled. These shots are seldom used in asthmatic patients because of the risk of severe asthma or generalised allergic reactions. We plan to examine human blood cell responses to couch grass pollen allergens before and after allergy shots with a preparation that includes couch grass pollen and rye grass pollen. A comparable control group of patients receiving only drug therapy will also be investigated. This study will identify dominant sites of couch grass pollen allergen immunoreactivity and reveal mechanisms of desensitisation. Based on this information, we will develop novel couch grass pollen proteins that retain the positive features needed for a successful desensitising vaccine but without the ability to bind to allergy antibodies and possibly cause severe adverse events such as asthma attacks. These preparations could be used to provide safer and more effective allergy treatments that can be used in hay fever sufferers and asthmatics.Read moreRead less
Immunological And Molecular Basis Of Anaphylaxis Caused By Peanut And Tree Nut Allergy
Funder
National Health and Medical Research Council
Funding Amount
$195,691.00
Summary
An allergy to nuts is estimated to affect 1% of the population and peanuts are the major cause of fatal food-induced anaphylaxis. Five deaths occurred in the UK in 1993 which attracted media attention to the gravity of this problem. Proteins in the nut trigger a massive immunological reaction that causes the body to go into anaphylactic shock in which all the major body systems shut down. Nut allergy usually presents in infancy and persists indefinitely. As nuts are used in a wider and less visi ....An allergy to nuts is estimated to affect 1% of the population and peanuts are the major cause of fatal food-induced anaphylaxis. Five deaths occurred in the UK in 1993 which attracted media attention to the gravity of this problem. Proteins in the nut trigger a massive immunological reaction that causes the body to go into anaphylactic shock in which all the major body systems shut down. Nut allergy usually presents in infancy and persists indefinitely. As nuts are used in a wider and less visible range of food products, sensitisation is increasing and occurring earlier. It has been proposed, wrongly, that peanut (groundnut) allergic patients do not suffer from allergy to tree nuts (hazel, almond, Brazil, walnut). However a British survey of 1250 patients suffering from peanut anaphylaxis revealed that 50% of people with peanut allergy are also allergic to other nuts confirming our own clinical observations. At present, unlike insect venom allergy, grass pollen allergy and house dust mite allergy, there is no preventative treatment available. We plan to explore peanut allergy and investigate cross-reactivity between peanuts and major tree nuts to attempt to identify an allergen(s) that could explain the molecular nature of the allergy and offer approaches to immunotherapy. This information is necessary if we are to achieve safe and effective allergy shots for patients with this life long and life-threatening allergy as well as assisting in the development of better diagnosticRead moreRead less
Mimotopes For The Investigation And Therapy Of Allergic Disease
Funder
National Health and Medical Research Council
Funding Amount
$203,296.00
Summary
10% of children now use regular asthma medication. The current treatments dampen allergic inflammation but 25% of asthmatic children, all under high medication, need multiple visits to the doctor, emergency treatment or hospitalisation,. Immunotherapy has, since 1911, used repeated injections of allergens. The end result has often been successful and lasting but the response has been unpredictable and requires years of multi-injection treatment. The challenge is to develop effective, applicable ....10% of children now use regular asthma medication. The current treatments dampen allergic inflammation but 25% of asthmatic children, all under high medication, need multiple visits to the doctor, emergency treatment or hospitalisation,. Immunotherapy has, since 1911, used repeated injections of allergens. The end result has often been successful and lasting but the response has been unpredictable and requires years of multi-injection treatment. The challenge is to develop effective, applicable immunotherapy which, like vaccines use few injections. Mimotopes provide a new opportunity. Studying the parts of the allergens recognized by the immune system (epitopes) can reveal important phenomena undetectable with whole allergens; and single epitopes may be a powerful avenue to effective immunotherapy. The therapy can be targeted to a selected arm of the immune system for maximal effect and the immediate side effects induced by cross linking antibodies with two epitopes can be avoided. Allergens interact with two types of lymphocyte, the T and B cells. T-cell epitopes can be easily studied because they comprise short regions of proteins which can be synthesized. B-cell (and antibody) epitopes are shapes formed by the interaction of several parts of a protein which cannot be represented by a simple sequence. The mimotope technology uses random peptides to obtain a shape which mimics the B-cell epitope. Here mimotopes will be produced and used to study the common specificities recognized in allergic responses to house dust mite allergens to develop new types of therapy. Importantly recent information shows that B-cell epitopes can be used to modify both T and B-cell function.Read moreRead less
T Cell PKC Expression As A Novel Neonatal Predictor And Modulator Of Allergic Disease.
Funder
National Health and Medical Research Council
Funding Amount
$557,939.00
Summary
This application will further assess the role of a novel biological predictor of allergic disease, which appears more accurate than any previous marker (based on preliminary data). This is highly relevant to development of predictive tools that could be ultimately used in clinical practice. We will also assess this marker as a potential target for disease prevention, as our preliminary data also indicates that it can be modified by an early intervention aimed at preventing allergic disease.
Inhibition Of Allergic Airway Inflammation By Nanoparticles
Funder
National Health and Medical Research Council
Funding Amount
$540,075.00
Summary
Inhaled air pollution particulate matter causes asthma exacerbations, with 'ultrafine' nanoparticles thought to play a major role. Unexpectedly, we recently found that, by contrast, administration of inert ultrafine nanoparticles prevents allergic airway inflammation. We will identify the key particle physical and chemical properties associated with this novel type of disease inhibition, study particle effects in clinically-relevant disease models and identify mechanisms of action.