Understanding Rapid T-cell Clearance By The Liver: A Critical Step Towards Improved Liver Transplantation.
Funder
National Health and Medical Research Council
Funding Amount
$412,134.00
Summary
The liver has paradoxical properties: it is the site of effective immune responses to pathogens, but under some circumstances, it is known to induce harmless immune responses. Poor responses can be beneficial in a transplantation setting because, in the absence of immunosuppressive drugs, liver transplants are more readily accepted than other organ allografts. Not only are liver transplants well accepted, they can induce secondary acceptance of kidney or heart grafts from the same donor that wou ....The liver has paradoxical properties: it is the site of effective immune responses to pathogens, but under some circumstances, it is known to induce harmless immune responses. Poor responses can be beneficial in a transplantation setting because, in the absence of immunosuppressive drugs, liver transplants are more readily accepted than other organ allografts. Not only are liver transplants well accepted, they can induce secondary acceptance of kidney or heart grafts from the same donor that would otherwise be rejected. However, this ability of the liver to induce unresponsiveness may allow some viruses to persist, particularly , Hepatitis B and C. Four in every five patients infected with hepatitis C develop a chronic disease due to the inability of the immune system to clear the virus. Although it is known that white blood cells enter the liver and become unresponsive, little is known about the mechanisms that prevent an effective response. The CIA s work has been at the forefront of liver immunology and transplantation by demonstrating that the architecture and vasculature of the liver, and therefore the type of unique cellular interactions taking place within it, are essential to gain an understanding of its unique immunological properties. Using the CIB s unique protocols for solid-organ transplantation in rodents, we will provide evidence for a new mechanism that occurs at very early stages after antigen encounter in the liver. We propose to unravel this mechanism using well characterised transgenic mouse models and advanced analytical technology. We will determine the role of this mechanism in liver transplantation. Our preliminary data point to a very high chance of success. This project will have important implications for transplantation studies and for the development and treatment of food allergies and chronic hepatitis C and other of immune-mediated liver diseases.Read moreRead less
Protecting Against Malaria Through Liver-resident Memory T Cells
Funder
National Health and Medical Research Council
Funding Amount
$1,196,853.00
Summary
We have shown that formation of liver-resident memory T cells (Trm), a newly discovered type of immune cells, can be induced by an innovative vaccination strategy called prime and trap for highly efficient protection against malaria in mice. Here, we will enhance prime and trap vaccination efficacy by defining the conditions that maximize liver Trm-mediated protection and will characterize simian and human liver Trm cells, paving the way to create the most efficient human malaria vaccine to date
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.
B Cell Survival And Responsiveness In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$664,584.00
Summary
I am an immunologist focused on identifying how B lymphocytes, the cells responsible for producing antibodies, survive and participate in immune responses within the body. I achieve this by using specially designed, genetically modified, mice that allow me to follow B lymphocytes within the body and identify their key genetic and external controls. My work is relevant to vaccine development as well as the control of certain autoimmune diseases and B lymphocyte cancers.
Influence Of TCR Signals From Contact With Self-MHC Ligands On Naive T Cell Survival
Funder
National Health and Medical Research Council
Funding Amount
$418,658.00
Summary
A diverse repertoire of naive T cells constitutes a critical part of the adaptive immune system and protects hosts from various infections and cancer. T cells are stably maintained at a constant number in the periphery by mechanisms that are not clearly understood. This proposal will shed light on how the immune system preserves a diverse na�ve T cell pool able to respond against various foreign antigens, while preventing their harmful auto-reactivity to self antigens.
The Axis Of Bcl-2, Plasmacytoid DCs And Lupus As A Basis For Therapy
Funder
National Health and Medical Research Council
Funding Amount
$712,172.00
Summary
Systemic lupus erythematosus (SLE) affects 1 in 1000 Australians, mostly women. Here the immune system goes awry and makes antibodies against the body’s own components including the body’s DNA. This leads to damage to many parts of the body including kidneys, joints, brain and heart. It is incurable. A particular immune cell controls the development of this disease and we have found this cell is selectively killed by an inexpensive drug, which we hope will be a better way of treating SLE.
CCR9 Expressing T Helper Cells In Immunity And Autoimmunity
Funder
National Health and Medical Research Council
Funding Amount
$729,571.00
Summary
We have identified a unique subset of immune cells in autoimmune lesions named Tccr9 cells. You find these cells in the gut, but when the body shifts into disease mode, Tccr9 cells disseminate to the accessory organs of the digestive system. Understanding the relationship between gut Tccr9 cells and the Tccr9 cells that contribute to chronic inflammation and autoimmunity is the focus of this research proposal.
Understanding Pathogenicity And Immunity In An Encephalitic Mouse Model Of Hendra Virus Infection
Funder
National Health and Medical Research Council
Funding Amount
$572,342.00
Summary
Our understanding of Hendra virus infection and immunity is extremely limited and has been hampered by a lack of appropriate animal models of disease and reagents. This Project will employ a newly-established mouse model to study encephalitis, the most life-threatening manifestation of this infection. We will use unique, state-of-the-art infrastructure and a plethora of mouse-specific reagents to investigate the mechanisms involved in regulating the host response to infection.