Control Of The Antigen-specific Cytotoxic T Cell Memory Response
Funder
National Health and Medical Research Council
Funding Amount
$95,044.00
Summary
Individuals who survive infections by a given pathogenic micro-organism are usually protected from subsequent infections by these same agents. This is the basis of adaptive immunity, which defines the body's ability to maintain a memory of prior infection or vaccination and in so doing, mount a far more effective response to subsequent infection by these agents. This proposal deals with the mechanisms by which this memory is maintained. It specifically focuses on cytotoxic T lymphocytes (CTL) wh ....Individuals who survive infections by a given pathogenic micro-organism are usually protected from subsequent infections by these same agents. This is the basis of adaptive immunity, which defines the body's ability to maintain a memory of prior infection or vaccination and in so doing, mount a far more effective response to subsequent infection by these agents. This proposal deals with the mechanisms by which this memory is maintained. It specifically focuses on cytotoxic T lymphocytes (CTL) which are leucocytes or white blood cells that kill virus infected cells. Using new technology which permits visualisation of CTL directed against specific viruses we are going to define what determines the survival and replacement of these memory cells over time. We will also identify the agents that alter the memory CTL's ability to deal with infections within localised sites in the body. In so doing, this work will provide valuable insight into approaches that can be used to better vaccinate individuals against infections by pathogenic viruses.Read moreRead less
Apoptosis Amongst Specific And Bystander T Cells In Chronic Bacterial Infection
Funder
National Health and Medical Research Council
Funding Amount
$317,545.00
Summary
When an infection occurs the immune cells (lymphocytes) proliferate in order to initiate and expand the immune response. If the body had no mechanisms to limit proliferation, the numbers of cells would soon overwhelm the body. Working with simple protein antigens rather than infection, other workers have found that once T lymphocytes have been activated and the immune response triggered, they soon undergo a process of self destruction called apoptosis. However, during infection, if the limits to ....When an infection occurs the immune cells (lymphocytes) proliferate in order to initiate and expand the immune response. If the body had no mechanisms to limit proliferation, the numbers of cells would soon overwhelm the body. Working with simple protein antigens rather than infection, other workers have found that once T lymphocytes have been activated and the immune response triggered, they soon undergo a process of self destruction called apoptosis. However, during infection, if the limits to lymphocyte proliferation are imposed before the infecting bacterium is eliminated, full expression of immunity does not occur and chronic infection may result. We believe that this contributes to the chronicity of such infections as tuberculosis and leprosy. We also suspect that, during infection, not only protective T lymphocytes proliferate, but also nonspecific bystander cells. This exaggerates the problem of lymphocyte proliferation and adds to immunopathology (immune damage). We have established an animal model of chronic bacterial infection in order to study how apoptosis is induced in T lymphocytes and how its adverse effects may be overcome. We hypothesize that apoptosis may be induced by one or more of a number of mechanisms, and that they may differ for the specific protective cells and the bystander cells. Once we understand the mechanisms apoptosis of specific lymphocytes may be prevented without harming the body. This has the potential to open new areas of immunotherapy (manipulating the immune response) of these diseases.Read moreRead less