Investigating The Mechanism And Consequences Of Cytotoxic Lymphocyte Detachment
Funder
National Health and Medical Research Council
Funding Amount
$419,180.00
Summary
Killer cells are white blood cells that destroy cancerous cells. To move to their next target they must quickly detach from a dying target. Failure of detachment results in excessive inflammation and tumour escape. This project will discover the detachment signals required to ‘release’ a locked-on killer cell. This will lead to a deeper understanding of immune pathology and new ways of treating cancer.
Characterisation Of T-cell Responses In Drug Hypersensitivity
Funder
National Health and Medical Research Council
Funding Amount
$306,338.00
Summary
Drug hypersensitivity reactions (DIHS) are a catastrophic form of adverse drug reaction. This study will use the drug abacavir, a cause of drug hypersensitivity to examine the way certain immune cells react and determine whether responses to viruses that are persistent in our bodies play a role these development of these reactions. This will help inform the immunological basis of DIHS as well as new treatments and potential ways of identifying drugs likely to cause these reactions in the pre-mar ....Drug hypersensitivity reactions (DIHS) are a catastrophic form of adverse drug reaction. This study will use the drug abacavir, a cause of drug hypersensitivity to examine the way certain immune cells react and determine whether responses to viruses that are persistent in our bodies play a role these development of these reactions. This will help inform the immunological basis of DIHS as well as new treatments and potential ways of identifying drugs likely to cause these reactions in the pre-marketing phase of drug development.Read moreRead less
Recruitment And Activation Of Alternatively Activated Macrophages By Thioredoxin Peroxidases In Helminth Infections
Funder
National Health and Medical Research Council
Funding Amount
$243,000.00
Summary
This research will unlock the immunological steps that lead to the development of pathological consequences associated with infectious pathogens and human diseases. The investigation proposed is very timely, as there is a rapid growth in people acquiring infectious diseases in the developing world and inflammatory pathologies in the developed world such as artherosclerosis, asthma, and tumour progression. There is a common denominator between all of these diseases. The body loses its ability to ....This research will unlock the immunological steps that lead to the development of pathological consequences associated with infectious pathogens and human diseases. The investigation proposed is very timely, as there is a rapid growth in people acquiring infectious diseases in the developing world and inflammatory pathologies in the developed world such as artherosclerosis, asthma, and tumour progression. There is a common denominator between all of these diseases. The body loses its ability to regulate a particular type of immune response, termed Th2. This results in the production of a chronic inflammation, which causes lasting damage. We have previously pinpointed the activity of a particular type of white blood cell, the macrophage, as pivotal to the induction of the Th2 immune response. We have also identified a molecule, thioredoxin peroxidase (TPx) that triggers the macrophage to switch on Th2 responses. Once the TPx comes into contact with the surface of the macrophage cell, a series of proteins, called transcription factors become activated in a controlled cascade. This leads to the secretion of substances from the macrophage, which signal the development of Th2. We will identify the mechanism that TPx uses to initiate the process. We propose to investigate this sequence of events by using an in-vitro cell based model to study the enzymatic steps as the macrophage responds to TPx. This goal represents much more than scientific curiosity. A better understanding of the process may reveal how TPx switches on the macrophage. If the trigger for this could be found, it would present a new way to manipulate the macrophage. This will possibly unearth new drug targets and lead to more effective therapeutics against infectious diseases, asthma, artherosclerosis and cancer.Read moreRead less
Population Dynamics Of Tissue-specific Effector And Regulatory CD4+ T Cells
Funder
National Health and Medical Research Council
Funding Amount
$394,250.00
Summary
Survival of white blood cells in the body is an active process and is important for the maintainence of a T cell population which can recognise a wide variety of foreign antigens. At present the fate of T lymphocytes which recognise self antigens is unclear. Knowledge of the survival kinetics of self-reactive T lymphocytes and the mechanism by which they are regulated in the normal individual is crucial to be able to control the development of various diseases, including autoimmune diseases. Fro ....Survival of white blood cells in the body is an active process and is important for the maintainence of a T cell population which can recognise a wide variety of foreign antigens. At present the fate of T lymphocytes which recognise self antigens is unclear. Knowledge of the survival kinetics of self-reactive T lymphocytes and the mechanism by which they are regulated in the normal individual is crucial to be able to control the development of various diseases, including autoimmune diseases. From our previous studies of autoimmune gastritis we have generated cell lines of lymphocytes that recognise stomach-specific antigens and with these unique reagents we will perform experiments to determine the fate of these self-reactive T cells in a normal individual. Also we will determine the impact of different amounts of the tissue antigens on the survival and activation of self-reactive T cells, and finally how a special class of lymphocytes, know as regulatory lymphocytes, act in vivo to control the activity of self-reactive T cells. We will use not only classical immunological approaches to address these issues but also state of the art imaging, to visualise the nature of the cell interactions in living tissues. The information arising from this work will underpin strategies to selectively turn off self-reactive lymphocytes that cause disease, will form the basis of clinical development of cell based therapies to treat autoimmune diseases, and the imaging technologies developed in this grant will have wide applicability to the study of a range of immune responses.Read moreRead less
During an immune response a white blood cell, the T lymphocyte, receives a series of signals that manipulate cell survival and proliferation. The team at WEHI will identify the effects of key signals on the molecular control of T cell survival. The results will be used to test a new method for inducing tolerance and dampening unwanted immune responses, such as during tissue graft rejection and autoimmunity.
Viral Antigen Presentation Kinetics And Memory T Cell Inflation
Funder
National Health and Medical Research Council
Funding Amount
$503,753.00
Summary
The ageing of the population is one of the major transformations being experienced by Australia’s population which will have major health implications. Recent studies have shown that many elderly individuals display ‘immune risk phenotype’ (IRP) which is characterised by a severely distorted immune system and human cytomegalovirus (CMV) infection. In this project we will investigate the mechanisms by which CMV alters cellular immune system and thus impacts on the host immunity against other path ....The ageing of the population is one of the major transformations being experienced by Australia’s population which will have major health implications. Recent studies have shown that many elderly individuals display ‘immune risk phenotype’ (IRP) which is characterised by a severely distorted immune system and human cytomegalovirus (CMV) infection. In this project we will investigate the mechanisms by which CMV alters cellular immune system and thus impacts on the host immunity against other pathogens.Read moreRead less