Investigating The Role Of TCR Avidity In Influenza Virus-specific CD8 T Cell Responses
Funder
National Health and Medical Research Council
Funding Amount
$83,142.00
Summary
One of the constituents of the immune system is the cytotoxic, or killer, T cells and these are important in the overall protection from viral infection. Activation of these T cells is mediated by signalling through the T cell receptor (TCR). This study will definitively determine how the strength with which the TCR binds to the activating ligand, can influence the quality of virus-specific T cell immune responses after infection. This has implications for vaccine design.
Molecular Regulation Of Tim3 Signalling In T Cells
Funder
National Health and Medical Research Council
Funding Amount
$366,252.00
Summary
Chronic inflammatory diseases like multiple sclerosis and cancer can be rectified via interventions of T cell checkpoint pathway. Tim3 is a T cell checkpoint molecule that is gaining extreme interest in these diseases. Here, we aim to identify molecular mechanism(s) to suppress or enhance Tim3 signalling in effector T cell, potentially leading to the development of therapeutic intervention to treat autoimmune disorders and cancers.
Antigen Dose And TCR Repertoire In CD8+ T Cell Immunodominance Hierarchies
Funder
National Health and Medical Research Council
Funding Amount
$558,920.00
Summary
The CD8+, or killer , T lymphocytes (white blood cells) are the hit men of immunity, recirculating continually around the body to eliminate other cells that are dangerous because they are cancerous or infected with a virus. A major difficulty is that killer T cells also exert selective pressures that cause viruses and tumours to mutate and thus avoid immune control. This is a particularly serious problem for RNA viruses that readily mutate as they divide. These include the human immunodeficiency ....The CD8+, or killer , T lymphocytes (white blood cells) are the hit men of immunity, recirculating continually around the body to eliminate other cells that are dangerous because they are cancerous or infected with a virus. A major difficulty is that killer T cells also exert selective pressures that cause viruses and tumours to mutate and thus avoid immune control. This is a particularly serious problem for RNA viruses that readily mutate as they divide. These include the human immunodeficiency virus (HIV) that causes AIDS and, while the mutations that are most important with influenza viruses are those that modify viral surface proteins recognized by antibodies, such T cell escape mutants can also be a problem with influenza. The other reason why there is particular interest in promoting CD8+ T cell-mediated immunity to influenza is that the killer T cells are very cross-reactive. We have shown that vaccination approaches that prime mouse CD8+ T cells to resist influenza A viruses circulating currently in humans will also protect against the highly lethal, and dangerous H5N1 bird 'flu. The present flu vaccines only stimulate antibodies, so there is interest in the possibility of a major re-design. The CD8+ T cells recognize tiny elements (peptides) of the virus or tumour bound in the tip of our own transplantation, or class I major histocompatibility complex (MHCI) molecules. These pMHCI complexes are called epitopes. The focus here is on the use of novel genetic engineering strategies to find out how, when the virus mutates to disrupt the major epitopes seen by killer T cells, other minor epitopes can be abnormally emphasized in a way that promotes effective immune control. As we work on this with the relatively simple and safe influenza model we will concurrently develop strategies that may be of value in HIV and tumour immunity. Solving this problem could prove to be a substantial advance in the design of vaccines and immunotherapy approaches.Read moreRead less
Characterisation Of Cell-mediated Immune Responses In Burkholderia Pseudomallei Infection
Funder
National Health and Medical Research Council
Funding Amount
$239,250.00
Summary
The bacterium Burkholderia pseudomallei, causes a life threatening condition known as melioidosis. Melioidosis is emerging as an important infectious disease in tropical regions of Australia and South East Asia. Death rates following acute disease are extremely high. Despite the importance of B. pseudomallei in tropical public health, very little is known regarding how the body's defence mechanisms prevent the spread of infection. The wide distribution of melioidosis in tropical Australia and ot ....The bacterium Burkholderia pseudomallei, causes a life threatening condition known as melioidosis. Melioidosis is emerging as an important infectious disease in tropical regions of Australia and South East Asia. Death rates following acute disease are extremely high. Despite the importance of B. pseudomallei in tropical public health, very little is known regarding how the body's defence mechanisms prevent the spread of infection. The wide distribution of melioidosis in tropical Australia and other parts of the world, and the lack of basic scientific information regarding this disease, has prompted this study. The bacterium lives within the body's cells and therefore does not respond well to standard antibiotic treatment. Although some of the basic immune mechanisms have been identified, how protection to the organism develops remains unclear. In this project we will investigate the effect of B. pseudomallei on immune cells or lymphocytes. This study will determine the patients' immune responses to the bacteria causing the disease. Our research team has already successfully carried out work on several different aspects of melioidosis. The characterisation of the basic immune function determined in the proposed study will provide the scientific basis for improvement in treatment and the development of possible preventive strategies against melioidosis.Read moreRead less
Targeting Vitamin-reactive T Cells For Enhanced Immunity
Funder
National Health and Medical Research Council
Funding Amount
$2,590,576.00
Summary
A specialised set of T cells called mucosal-associated invariant T (MAIT) cells react against bacteria and yeast, and reside at mucosal sites where the body's immune defences are often breached, e.g. respiratory tract and intestinal mucosa. This study seeks to define the molecular signals driving the function of MAIT cells, particularly during infections. This information may lead to methods tailored to manipulating MAIT cells therapeutically.
Interplay Of Innate And Adaptive Immunity To Influenza A Virus
Funder
National Health and Medical Research Council
Funding Amount
$555,693.00
Summary
Influenza is an acute febrile respiratory illness caused by influenza virus infection, and may trigger potentially life-threatening complications especially in the young and elderly. Immunity against influenza virus involves integration of the innate and adaptive immune system. We will use cutting-edge 2-photon microscopy to determine the orchestration of innate and adaptive immune cell interactions during viral infection. Results may provide for enhanced therapeutic or protective measures.
We have identified a population of immune cells called ‘resident memory T cells’ that reside in tissues of the body. These resident memory T cells play an important role in controlling infections, but it is also apparent that they can lead to aberrant immune reactions, causing autoimmune diseases. This project aims to further our understanding of these immune cells, including how they can be identified and generated, and how they can be controlled to prevent disease.
Delineating Immune Circuits For Innate And Adaptive Immune Protection
Funder
National Health and Medical Research Council
Funding Amount
$876,005.00
Summary
The immune system provides the essential frame-work to protect us against infection, disease and to heal tissues after trauma. This is achieved by a complex but elegant network of different types of white blood cells. Understanding the molecular wiring of these cells will provides fundamental insights to how the body fights pathogen infections and cancer and lays the foundation to therapeutic approaches to vaccination and disease treatments.