Determining The Role Of Rel/NF-kB Transcription Factors In CD8 T Cell Homeostasis.
Funder
National Health and Medical Research Council
Funding Amount
$426,500.00
Summary
NF-kB proteins comprise a family of transcription factors that regulate key genes involved in immune responses, inflammation, cell death and proliferation. This family of proteins are potential drug targets for treatment of various diseases. How and when such inhibitors are used in clinical situations depends on understanding how and which cells of the immune system are specifically affected by the absence of NF-kB proteins. In a number of treatment settings intercurrent viral infections occur f ....NF-kB proteins comprise a family of transcription factors that regulate key genes involved in immune responses, inflammation, cell death and proliferation. This family of proteins are potential drug targets for treatment of various diseases. How and when such inhibitors are used in clinical situations depends on understanding how and which cells of the immune system are specifically affected by the absence of NF-kB proteins. In a number of treatment settings intercurrent viral infections occur frequently and therefore there is an even greater need to understand how the immune system may be affected or compromised in response to the primary treatment. This work will provide insights into the cellular and molecular mechanisms affected by the absnece of a particular NF-kB family member (NF-kB1) in CD8 T cells during normal T cell homeostasis and when challenged with viruses. What we learn from our experiments could have important implications for the development of vaccines.Read moreRead less
Role Of DC-NK Cross-talk In Viral Infection: Defining The Critical Molecular Mechanisms
Funder
National Health and Medical Research Council
Funding Amount
$519,000.00
Summary
Dendritic cells (DC) are a highly specialized subset of cells involved in activating the immune system in response to infection. Dendritic cells can activate T cells, which then destroy infected or damaged cells. Recent evidence has suggested that activation of natural killer (NK) cells may also be an important function of dendritic cells. NK cells specialize in the removal of damaged cells and have been shown to be particularly important in controlling viral infection and tumour growth and spre ....Dendritic cells (DC) are a highly specialized subset of cells involved in activating the immune system in response to infection. Dendritic cells can activate T cells, which then destroy infected or damaged cells. Recent evidence has suggested that activation of natural killer (NK) cells may also be an important function of dendritic cells. NK cells specialize in the removal of damaged cells and have been shown to be particularly important in controlling viral infection and tumour growth and spread. The central aim of this work is to determine what mechanisms are used by dendritic cells to activate NK cells during viral infection. The well characterized murine cytomegalovirus model (MCMV) will be used to address this question. MCMV is a model for human cytomegalovirus infection (HCMV). HCMV infection usually poses no risk to healthy individuals, however, in people who are immunosuppressed, such as cancer or AIDS patients, HCMV is a significant cause of mortality. The MCMV infection model has provided important insights as to how the immune system controls infection, and the mechanisms utilized by the virus to circumvent these processes. The proposed studies will enhance our understanding of how natural killer cell function is regulated by dendritic cells, and how viruses may interfere with this process. More importantly, the results will provide critical insights into how immunotherapy protocols may be modified to enhance effectiveness.Read moreRead less
Do NK Cells Limit The Long Term Burden Of CMV In Older Australians And Transplant Recipients?
Funder
National Health and Medical Research Council
Funding Amount
$413,864.00
Summary
Most people are infected with cytomegalovirus at an early age. The virus is not naturally cleared from the body but becomes latent and may be reactivated by stress or inflammation. Repeated immune responses to these reactivations causes more inflammation and wears out the immune system resulting in diseases of aging (eg: cardiovascular disease). Here we investigate which aspects of the immune system can control CMV in healthy people and in renal transplant recipients. We focus on a population of ....Most people are infected with cytomegalovirus at an early age. The virus is not naturally cleared from the body but becomes latent and may be reactivated by stress or inflammation. Repeated immune responses to these reactivations causes more inflammation and wears out the immune system resulting in diseases of aging (eg: cardiovascular disease). Here we investigate which aspects of the immune system can control CMV in healthy people and in renal transplant recipients. We focus on a population of cells called natural killer (NK) cells.Read moreRead less
Perforin is a cytolytic protein found in cytotoxic lymphocytes. It plays an essential role in the destruction of virus- and pathogen- infected cells as well as tumour cells. Perforin deficiency in humans and experimental animals results in the loss of resistance to many viral infections and dramatically increases the chance of spontaneous tumour formation. Whilst perforin was first characterised two decades ago, its mechanisms of action remain unknown. The current Grant Proposal will capitalise ....Perforin is a cytolytic protein found in cytotoxic lymphocytes. It plays an essential role in the destruction of virus- and pathogen- infected cells as well as tumour cells. Perforin deficiency in humans and experimental animals results in the loss of resistance to many viral infections and dramatically increases the chance of spontaneous tumour formation. Whilst perforin was first characterised two decades ago, its mechanisms of action remain unknown. The current Grant Proposal will capitalise on some recent key technological advances in our laboratory that are enabling us to investigate the mechanisms and the regulation of perforin function. Our recent advances in the field put us in a pre-eminent international position to conduct these studies. In broader terms, the proposed studies will have an immediate impact on our understanding of the mechanisms of cytotoxic lymphocyte regulated immune response and on immune homoeostasis in general. It will also improve our understanding of defence mechanisms against various pathogens and will provide more insight into the role of immune system in protection of the organism against cancer.Read moreRead less
The liver is an important organ in terms of immune responses. Owing to its exposure to many antigens, it is required to maintain a form of immune tolerance. This ensures that overt immune responses which would damage the liver do not occur. One means by which tolerance occurs is through silencing killer cells through the regulation of molecules of Major Histocompatibility Complex (MHC). This project will explore the role of a soluble form of MHC which is expressed only in the liver.
Antigen Presentation, Recognition And The Immune Response
Funder
National Health and Medical Research Council
Funding Amount
$14,927,045.00
Summary
This program focuses on understanding the development of immunity during infection or inflammatory diseases using a broad array of techniques to dissect the function of various immune cell types and to explore the relationship between structure and function of important cell surface molecules. These studies will improve our ability to design new generation vaccines for combating infectious diseases, controlling cancer, or limiting autoimmune or inflammatory diseases.
Antigen Presentation, Recognition And The Immune Response
Funder
National Health and Medical Research Council
Funding Amount
$15,780,848.00
Summary
This program focuses on understanding the development of immune response to viruses and other infectious agents using a broad array of techniques to dissect the function of various immune cell types and to explore the relationship between structure and function of important cell surface molecules. These studies will improve our ability to design new generation vaccines for combating infectious diseases, controlling cancer, or limiting autoimmune diseases like diabetes.