Mechanisms Of Rapid Memory CD8+ T-cell Inactivation
Funder
National Health and Medical Research Council
Funding Amount
$318,517.00
Summary
Type 1 diabetes (T1D) and other autoimmune diseases results from misdirected immune responses that destroy normal body tissues. The ultimate goal of therapeutic strategies is to remove or inactivate the immune cells that attack normal tissues, while leaving other immune cells, for example, those required for protection from infectious diseases and tumours, unaffected. Here we propose to test a new way of turning off inappropriate immune reactions.
The Role Of Alloantigen Presentation In Transplantation
Funder
National Health and Medical Research Council
Funding Amount
$508,003.00
Summary
Bone marrow transplantation (BMT) is the most effective treatment for a number of haematological conditions, especially leukemia. Graft versus host disease (GVHD) is a complication of BMT and results in the death of up to 50% of transplant recipients. GVHD occurs when the newly transplanted immune system recognizes the recipient as foreign and mounts and immune reponse against the patients tissues. These studies will focus on identifying and understanding the function of the immune cells which d ....Bone marrow transplantation (BMT) is the most effective treatment for a number of haematological conditions, especially leukemia. Graft versus host disease (GVHD) is a complication of BMT and results in the death of up to 50% of transplant recipients. GVHD occurs when the newly transplanted immune system recognizes the recipient as foreign and mounts and immune reponse against the patients tissues. These studies will focus on identifying and understanding the function of the immune cells which drive GVHD.Read moreRead less
Tumour Antigen Cross-presentation: Efficiency, Biology And Role Of Inhibitory B7 Homologue Molecules
Funder
National Health and Medical Research Council
Funding Amount
$469,500.00
Summary
It is now known that the body s immune system often attempts to attack cancers but this response is generally fairly weak. It was previously thought that one of the main reasons for this failure was that the immune system was ignorant of the presence of the cancer until too late. Our recent work over the past few years has shown that this is not the case. A process called cross-presentation seems to efficiently and continuously expose the cancer to the body s anti-cancer killer T-cells. This gra ....It is now known that the body s immune system often attempts to attack cancers but this response is generally fairly weak. It was previously thought that one of the main reasons for this failure was that the immune system was ignorant of the presence of the cancer until too late. Our recent work over the past few years has shown that this is not the case. A process called cross-presentation seems to efficiently and continuously expose the cancer to the body s anti-cancer killer T-cells. This grant will work out exactly how efficient that process is, which cells are responsible and some aspects of how it happens. We will also study whether some recently-discovered braking molecules, which slow down immune responses and which could be 'applying the brakes' to anti-cancer responses. This could lead to new approaches to therapy eg by removing these brakes during vaccination therapy.Read moreRead less
Regional Immunosuppression For Corneal Transplantation
Funder
National Health and Medical Research Council
Funding Amount
$268,264.00
Summary
Blindness exerts major physical, emotional and economic constraints and hardship upon the sufferer. Corneal transplantation is a well-accepted surgical treatment for visual impairment caused by opacification of the cornea, the transparent window at the front of the eye. Corneas for transplantation are retrieved from people who have recently died, after permission has been sought from the donor's family. Unfortunately, a significant proportion of corneal transplants fail because they are recogniz ....Blindness exerts major physical, emotional and economic constraints and hardship upon the sufferer. Corneal transplantation is a well-accepted surgical treatment for visual impairment caused by opacification of the cornea, the transparent window at the front of the eye. Corneas for transplantation are retrieved from people who have recently died, after permission has been sought from the donor's family. Unfortunately, a significant proportion of corneal transplants fail because they are recognized as foreign, and undergo rejection by the recipient. Once a corneal graft has failed, it is no longer transparent to light. A number of novel interventions are being developed to reduce the incidence of corneal graft rejection, but at present it is uncertain exactly how these should be delivered to the patient. The research described in this application is designed to discover how therapeutic agents and interventions can best be targeted, to prevent corneal graft rejection. Overcoming an unwanted immune response would improve the outcome of corneal transplantation by as much as thirty percent.Read moreRead less
The Cell Biology Of Macropinocytosis Pathways In Antigen Presenting Cells
Funder
National Health and Medical Research Council
Funding Amount
$545,216.00
Summary
Cells internalise molecules in membrane-bound vesicles, a process known as endocytosis. This internalisation pathway is essential for many biological events, including the ability to capture foreign antigens and mount an effective immune response. Some internalisation pathways can be switched on by signals received at the cell surface. This study will identify the molecules that control antigen capture in immune cells. This knowledge is important for the development of better vaccines.
Studies Of Antigen Presenting Cells In The Anterior Segment Of The Eye And Their Role In Immune-mediated Ocular Disease
Funder
National Health and Medical Research Council
Funding Amount
$241,018.00
Summary
Dendritic cells (DC) are considered the 'sentinels' of the immune system because they are capable of trapping antigenic material derived from invading organisms such as bacteria and viruses in peripheral tissues-organs (skin, gut, respiratory tract etc) and then transporting these antigens to the lymphoid organs where they 'alert' the immune system to potential 'dangers' and elicit appropriate T cell responses. If the antigens are novel this mechanism forms the basis of primary cell-mediated imm ....Dendritic cells (DC) are considered the 'sentinels' of the immune system because they are capable of trapping antigenic material derived from invading organisms such as bacteria and viruses in peripheral tissues-organs (skin, gut, respiratory tract etc) and then transporting these antigens to the lymphoid organs where they 'alert' the immune system to potential 'dangers' and elicit appropriate T cell responses. If the antigens are novel this mechanism forms the basis of primary cell-mediated immune responses. Previously 'educated' T cells may upon contact with antigens in the periphery (when presented by other antigen presenting cells [APCs], such as macrophages) become activated. This forms the basis for secondary immune responses. Immune and inflammatory responses in the eye are held in check to avoid permanent damage to the delicate tissues and maintain visual function. The mechanisms which regulate immunological responses in the eye are only now becoming clear. Studies in the Chief Investigators laboratory over the last 7 years have been aimed at unravelling the life cycle and function of APCs in the eye. The present study has three specific aims: 1) Determining whether DC in the eye once they have taken up antigens migrate to the spleen or local lymph nodes? 2) The second aim of this project is to use an animal model of uveitis and transfer fluorescent labelled donor T cells to study the events in the living eye which lead to autoimmune uveoretinitis. In particular we wish to identify the cells that present antigen to infiltrating lymphocytes. 3) Patients often develop posterior uveitis (an autoimmune condition) after a cold or bacterial infection. We aim to mimic conditions of acute inflammation in the eye to see whether this may secondarily predispose the eye to attack by autoreactive lymphocytes.Read moreRead less
Defining The Dynamics And Function Of Dendritic Cells After Cutaneous HSV Infection In Vivo.
Funder
National Health and Medical Research Council
Funding Amount
$419,223.00
Summary
Herpes simplex viral causes infections of the skin, eye, brain, genitals and of the newborn. HSV enters via breaks in the skin where it encounters dendritic cells, which are important for local control of the virus locally and for T cell responses. We will use two photon microscopy to visualise fluorescent HSV in mice in which DC appear green under the microscope. This will help us understand the interaction between HSV and DC in vivo which will aid design of topical antivirals and vaccines.