Antigen Receptor Sharing By Lymphocytes During An Immune Response
Funder
National Health and Medical Research Council
Funding Amount
$286,328.00
Summary
A successful immune response relies on the ability of immune cells to quickly mount a specific offensive against invading foreign pathogens like bacteria or viruses. The specificity of this offensive is governed by receptors that can recognise pathogens. To survive an infection the immune system must rapidly expand the number of immune cells that have receptors that recognise, and can therefore specifically combat, the infection. The underlying theory of immunology, the clonal selection theory, ....A successful immune response relies on the ability of immune cells to quickly mount a specific offensive against invading foreign pathogens like bacteria or viruses. The specificity of this offensive is governed by receptors that can recognise pathogens. To survive an infection the immune system must rapidly expand the number of immune cells that have receptors that recognise, and can therefore specifically combat, the infection. The underlying theory of immunology, the clonal selection theory, states that this expansion is mediated by the proliferation of immune cells selected on the basis of expressing a pathogen specific receptor. We hypothesise that in addition to this proliferation the immune system may also expand the number of immune cells expressing pathogen-specific receptors by transferring these receptors between cells by a means of cell-membrane sharing. Indeed, we have evidence that this does occur both in the test tube and in animals and can function to amplify the number of immune cells that can specifically recognise a pathogen and thereby help with immune response development. This grant aims to further advance our understanding of this novel phenomenon.Read moreRead less
The Molecular Basis Of HLA-linked Drug Hypersensitivity
Funder
National Health and Medical Research Council
Funding Amount
$827,536.00
Summary
Adverse drug reactions are one of the leading causes of death in hospitalised patients. We discovered a new mechanism that links these reactions to recognition of drug induced changes in immunological self, resulting from interactions of drugs with immune receptors. This project continues to probe the mechanisms of immune mediated drug reactions by examining the basis of life threatening reactions to drugs used to treat epilepsy, gout and commonly used drugs such as penicillin and aspirin.
The Mezzanine T Cell Response: Intervening At The Coal Face
Funder
National Health and Medical Research Council
Funding Amount
$765,585.00
Summary
In an initial immune response, specialised cells in lymph nodes tell T cells to multiply; the stimulated T cells depart and enter target tissue (e.g. lung in the case of flu). We describe a new response whereby the target tissue itself can tell T cells to multiply further. This response in target tissues reveals a new way of altering immune responses. This is especially important as in many diseases, the primary lymph node response has already occurred, so cannot be therapeutically intervened.
Antigen-presenting cells control immune responses. Different types of these cells do different jobs and affect different diseases. We wish to control these processes by determining how the cells live and die. In particular we are interested in controlling the local immune responses during rejection of islet transplantation, which can cure type 1 diabetes.
Mechanisms Of Rapid Memory CD8+ T-cell Inactivation
Funder
National Health and Medical Research Council
Funding Amount
$318,517.00
Summary
Type 1 diabetes (T1D) and other autoimmune diseases results from misdirected immune responses that destroy normal body tissues. The ultimate goal of therapeutic strategies is to remove or inactivate the immune cells that attack normal tissues, while leaving other immune cells, for example, those required for protection from infectious diseases and tumours, unaffected. Here we propose to test a new way of turning off inappropriate immune reactions.
Characterisation Of An Antigen Presenting Cell Unique To Spleen
Funder
National Health and Medical Research Council
Funding Amount
$420,606.00
Summary
The body depends on a range of defence mechanisms to remove invaders that enter by various routes. Antigen presenting cells are central to immunity in that they engulf and destroy dead cells and pathogens and present pieces of those pathogens or 'antigens' to white blood cells called T and B lymphocytes. These cells then start to fight the infection or disease. A new type of antigen presenting cell will be investigated for its particular ability to arrest blood-borne pathogens and disease.
Transcriptional Regulation Of Specialized Subsets Of Dendritic Cells In Control Of Infection
Funder
National Health and Medical Research Council
Funding Amount
$616,912.00
Summary
Immune protection against viruses and bacteria depends on specialized cells called dendritic cells that display components of the invading organisms on their surface. There are multiple different types of dendritic cell and each population plays a specialized role in defending the body against infection. Our work will provide the framework for directly targeting these cells for novel vaccines to re-program the immune system for clinical conditions such as cancer, allergy and autoimmunity.
Enhancing Vaccine Efficacy By Harnessing Dendritic Cell Receptors And Their Unique Properties
Funder
National Health and Medical Research Council
Funding Amount
$687,519.00
Summary
Potent vaccination might be achieved by using monoclonal antibodies as magic bullets to target vaccines to special cells in the body. We show that targeting these special cells by using monoclonal antibodies that recognise Clec9A is effective, perhaps because it brings several different immune cells together so that they orchestrate very efficient immune responses. This application investigates how targeting Clec9A allows strong vaccination so that we can apply this to new generation vaccines.