Quantification Of Antigen Presentation To CD8 T Cells During Virus Infection
Funder
National Health and Medical Research Council
Funding Amount
$582,072.00
Summary
Knowledge of how virus-infected cells are detected by the bodyÍs immune system is fundamental to our understanding of virus infections and attempts to improve vaccines. We know that many proteins are displayed during virus infection but until now, the precise details of this display have only been worked out for very few proteins, studied one at a time. In this project we will apply cutting-edge technology to gain the first holistic view of how a virus-infected cell looks to the immune system.
Cancer immunotherapy by “checkpoint blockade” boosts the immune response and leads to tumour rejection in some patients. To improve immunotherapy, information will be sought on the capacity of membrane vesicles prepared from dendritic cells (DC) to stimulate immune cells (T cells) in mice and elicit tumour rejection. Experiments are proposed to trace the fate of the vesicles after injection and improve tumour rejection by combination with checkpoint blockade and addition of cytokines.
The Mechanisms Of Establishing, Maintaining Immunological Memory And Immunodominance Hierarchy
Funder
National Health and Medical Research Council
Funding Amount
$234,750.00
Summary
The hallmark of the adaptive immune response is the development of specific immunological memory following the first confrontation with a microorganism. Memory T cells are capable of responding rapidly upon subsequent exposure to the same microbes thus providing protective immunity. This proposal aims to investigate how cytotoxic T cells establish memory following their primary encounter with microorganisms. The proposal will dissect the relationship between memory T cell formation and the amoun ....The hallmark of the adaptive immune response is the development of specific immunological memory following the first confrontation with a microorganism. Memory T cells are capable of responding rapidly upon subsequent exposure to the same microbes thus providing protective immunity. This proposal aims to investigate how cytotoxic T cells establish memory following their primary encounter with microorganisms. The proposal will dissect the relationship between memory T cell formation and the amount-length of antigen exposure; and the influence on memory induction from various immune modulators (cytokines) at the time of antigen encounter. Using a range of sophisticated detection methods, very early memory T cells will be identified in the primary response and tracked through their differentiation into long-term memory pool. Experiments will determine how T cells against particular determinants are selected from the primary immune response, retained in the memory pool and recalled in the subsequent challenges. The properties of antigen processing of various determinants will be correlated with the immunodominance hierarchy in the primary and memory response. Taken together the proposed project is central to understanding how memory T cells are created and what rules govern their stability. The project is highly relevant to vaccine design against tumours and pathogensRead moreRead less
Priming, Recruitment And Retention Of Influenza Virus Specific CD8 T Cells In The Upper Airways
Funder
National Health and Medical Research Council
Funding Amount
$633,371.00
Summary
Influenza virus gains entry into the body by inhalation and initiates its replication cycle within the upper airways. This early stage of infection, when the amount of influenza virus is low, provides the ideal window of opportunity for an effective immune response to limit disease progression. In this proposal we will define the immunity that can be evoked within the upper airways and determine immune mechanisms left behind that can safeguard this region from this important respiratory pathogen
We know that many parts of viruses are displayed to the immune system, but infection can also result in the display of fragments of our body's own proteins (self-peptides). We will apply cutting-edge technology to find all the virus- and self-peptides that are recognised by the immune system during infection with a vaccine virus and influenza virus. This will help us understand how the body fights infection and perhaps why infection can sometimes start autoimmune diseases.
Immunoregulation Of Subsets Of Memory CD8+ T Cells
Funder
National Health and Medical Research Council
Funding Amount
$233,867.00
Summary
Information will be sought on the properties of T cells, a class of white blood cells that play a vital role in combating infectious agents. Using mouse models, subsets of T cells that carry immunological memory will be studied and assessed for their rate of cell division and dependence on soluble messengers known as cytokines and other stimuli. The data will provide useful knowledge on the causes of autoimmune diseases (such as rheumatoid arthritis, type 1 diabetes and lupus) and help in the de ....Information will be sought on the properties of T cells, a class of white blood cells that play a vital role in combating infectious agents. Using mouse models, subsets of T cells that carry immunological memory will be studied and assessed for their rate of cell division and dependence on soluble messengers known as cytokines and other stimuli. The data will provide useful knowledge on the causes of autoimmune diseases (such as rheumatoid arthritis, type 1 diabetes and lupus) and help in the development of successful second generation vaccines.Read moreRead less
The Molecular Basis Of HLA-linked Drug Hypersensivity Reactions
Funder
National Health and Medical Research Council
Funding Amount
$683,040.00
Summary
Adverse drug reactions are one of the leading causes of death in hospitalised patients. We have 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 probes the generality of this mechanism by examining the basis of life threatening reactions to drugs used to treat epilepsy (carbamazepine), gout (allopurinol), HIV (Nevirapine) and towards aspirin a commonly used ....Adverse drug reactions are one of the leading causes of death in hospitalised patients. We have 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 probes the generality of this mechanism by examining the basis of life threatening reactions to drugs used to treat epilepsy (carbamazepine), gout (allopurinol), HIV (Nevirapine) and towards aspirin a commonly used pharmaceutical.Read moreRead less