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.
Competition For Polarity Influences Lymphocyte Differentiation And Function
Funder
National Health and Medical Research Council
Funding Amount
$380,558.00
Summary
CD46 is a protein on human cells that viruses and bacteria bind to during infection. Our laboratory has found that binding of CD46 on immune cells impairs their ability to recognize and kill target cells and may explain the immunosuppression caused by measles infection. We aim to investigate the mechanisms behind the effect of CD46 on immune cells. The outcomes of this study will define new paradigms in lymphocyte biology and determine how CD46 influences the immune response to infection.
The Role Of Epigenetic And Transcriptional Regulation In CD8+ T Cell Effector Gene Expression.
Funder
National Health and Medical Research Council
Funding Amount
$72,571.00
Summary
All cells contain DNA that is tightly wrapped around proteins, whereby changes in the structure allow for the expression of proteins. Cells of the immune system express proteins that can resolve viral infections. This study plans to examine the factors mediating the changes in DNA that allow for the expression of these proteins in immune cells. Insights will enable a greater understanding of how these proteins are generated and maintained, and hence will have implications for vaccine design.
Molecular Basis Of T Cell Receptor Bias In Viral Immunity
Funder
National Health and Medical Research Council
Funding Amount
$540,075.00
Summary
Viral infection results in the activation and proliferation of T cells that eradicate infected cells. Recognition of infected cells is meditated by presentation and recognition of viral protein fragments via specific cell surface receptors. This proposal plans to examine the factors that determine the diversity of the immune response and the consequences of such diversity on anti-viral immunity. This has implications for the development of vaccines.
Immunopathogenesis Of West Nile Virus Encephalitis - Requirement For Interferon-gamma-dependent Soluble Mediators
Funder
National Health and Medical Research Council
Funding Amount
$250,500.00
Summary
Flaviviruses transmitted by arthropods cause considerable illness and death world-wide by their propensity to cause encephalitis. In August 1999, an outbreak of West Nile virus (WNV) encephalitis occurred in New York for the first time, indicating that these viruses are spreading beyond endemic areas. However, the mechanisms by which these viruses kill people are not at all clear. How the immune system deals with them is controlled by a complex network of interactions involving cells and soluble ....Flaviviruses transmitted by arthropods cause considerable illness and death world-wide by their propensity to cause encephalitis. In August 1999, an outbreak of West Nile virus (WNV) encephalitis occurred in New York for the first time, indicating that these viruses are spreading beyond endemic areas. However, the mechanisms by which these viruses kill people are not at all clear. How the immune system deals with them is controlled by a complex network of interactions involving cells and soluble mediators such as cytokines, chemokines, and nitric oxide, many induced or modulated by the cytokine, inteferon-gamma. Evidence suggests that these agents together influence both the types of cells that are mobilised to eradicate virus and also disease outcomes. Our hypothesis is that the host's own immune system is inadvertently responsible for encephalitis through an over-vigorous attempt to destroy the infecting virus, resulting in damage to the brain. To study WNV encephalitis, we are using a mouse model developed in this laboratory that reproduces the features of human disease. Another strain of these mice has the gene for interferon-gamma (IFN) inactivated or 'knocked out', so they cannot respond in the conventional way to virus infection. This mouse survives WNV infection significantly better than normal mice and becomes immune. Therefore we will compare cellular and soluble mediator responses of these mice during WNV infection to those of normal mice. We will also delete specific cell types making interferon-gamma in normal mice, as well as transfering such cells into knockout mice. Experiments will indicate which cell types are responsible and when particular components cause most damage. Thus, we will better understand how interferon-gamma recruits cells that mediate immune brain damage in this model. By understanding the events that lead to death in encephalitis, it may be possible to prevent or ameliorate them by means of immune intervention.Read moreRead less
I am an cellular immunologist determining the mechanisms by which immunity to foreign organisms is generated, how tolerance to self tissues is maintained, and how the immune system iscriminates between foreign organisms and self.
While current influenza vaccines blunt winter epidemics, they must be updated frequently to keep up with virus mutation and they do not protect against pandemics caused by new flu viruses (such as bird flu). This program will define how flu virus interacts with the immune system to generate immunity mediated particularly by “killer” T cells. We will use this knowledge to develop and evaluate vaccines that induce long-lasting T-cell immunity that can protect against both seasonal and pandemic flu ....While current influenza vaccines blunt winter epidemics, they must be updated frequently to keep up with virus mutation and they do not protect against pandemics caused by new flu viruses (such as bird flu). This program will define how flu virus interacts with the immune system to generate immunity mediated particularly by “killer” T cells. We will use this knowledge to develop and evaluate vaccines that induce long-lasting T-cell immunity that can protect against both seasonal and pandemic flu.Read moreRead less
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.
Viral Reservoirs:Role Of Naive T-cells In The Pathogeneisis Of T-cell Decline And Longterm Persistence Of HIV Infection.
Funder
National Health and Medical Research Council
Funding Amount
$85,716.00
Summary
Despite dramatic advances in treatment for HIV infection, HIV cannot be cured. The main reason why cure is not possible is because HIV can persist in long lived cells and these infected cells are not recognised by the immune system. This project will examine the role of a particular type of infection fighting cell, the naive T-cell, in long term persistence of HIV. The project will determine how naive T-cells are infected with HIV and what happens to these cells following HIV treatment.