Members Of The CMRF-35 Leukocyte Receptor Complex On Human Chromosome 17q22-24 Modulate Immune Function
Funder
National Health and Medical Research Council
Funding Amount
$489,750.00
Summary
We have identified and characterized a group of proteins on the surface of different white blood cells called the CMRF-35 molecules. We hypothesize that these molecules play a role in regulating an immune response by acting as thermostat molecules i.e. molecules able to trigger or inhibit the immune response. This project aims to define the role of two of these molecules in regulating white blood cells in their response to foreign molecules or antigens. This project will have significant impact ....We have identified and characterized a group of proteins on the surface of different white blood cells called the CMRF-35 molecules. We hypothesize that these molecules play a role in regulating an immune response by acting as thermostat molecules i.e. molecules able to trigger or inhibit the immune response. This project aims to define the role of two of these molecules in regulating white blood cells in their response to foreign molecules or antigens. This project will have significant impact on understanding whether these triggering and inhibitory signals initiated from the CMRF-35 molecules effects i) how the cells divide, ii) what molecules are secreted by the cells, iii) whether the cells can mature or iv) whether a cell survives or dies. Some of the molecules involved in sending these signals will be identified. The ability to trigger or inhibit cellular effects through these molecules may be important in some forms of myeloid leukemia and in the ability to help manipulate the immune response to fight tumors.Read moreRead less
Immune Regulation During Uncomplicated And Severe P. Falciparum And P. Vivax Malaria
Funder
National Health and Medical Research Council
Funding Amount
$292,639.00
Summary
Malaria is a major global disease that kills over 1 million people every year. Immune responses induced during infection help fight the infection but can also cause tissue damage and thereby worsen disease. This study will determine differences in cellular immune responses during uncomplicated and severe malaria. Better understanding of the role of immune cells in response to infection and disease progression will assist the development of novel treatment interventions and vaccine development.
How IL-4 Suppresses TNF And IL-1 Production By Activated Human Monocytes And Macrophages
Funder
National Health and Medical Research Council
Funding Amount
$432,750.00
Summary
Chronic inflammatory diseases are an enormous and growing health problem. There is a continuing search for improved and more targeted treatments. We have been studying a cytokine called interleukin-4 which can suppress the production by blood cells of many of the inflammatory mediators that initiate and maintain inflammation. With the recognition that interleukin-4 has this anti-inflammatory activity on blood cells, there was considerable optimism that this molecule may not only be a natural reg ....Chronic inflammatory diseases are an enormous and growing health problem. There is a continuing search for improved and more targeted treatments. We have been studying a cytokine called interleukin-4 which can suppress the production by blood cells of many of the inflammatory mediators that initiate and maintain inflammation. With the recognition that interleukin-4 has this anti-inflammatory activity on blood cells, there was considerable optimism that this molecule may not only be a natural regulator of inflammation but also used in immunotherapy. However we do not know how this molecule downregulates inflammatory blood cells. It will be necessary to know this if it is to be used in human gene therapy for treatment of inflammatory diseases. Cells must be activated before a molecule which is anti-inflammatory can be effective. Different cell types from different inflammatory sites will be studied to better characterise different activation pathways. How interleukin-4 regulates these pathways will be studied. Once identified, treatments based on the properties of interleukin-4 may be designed-optimised.Read moreRead less
T cells are a central component of the immune system and without T cells the body is very vulnerable to infections. One subgroup of T cells is the killer T cells that are important for identifying and killing cells infected by viruses and bacteria. The immune system works to maintain T cell numbers at a fairly constant level and part of this process includes sending signals to the killer T cells from other cells via cell surface protein interactions and soluble mediators, such as cytokines. We h ....T cells are a central component of the immune system and without T cells the body is very vulnerable to infections. One subgroup of T cells is the killer T cells that are important for identifying and killing cells infected by viruses and bacteria. The immune system works to maintain T cell numbers at a fairly constant level and part of this process includes sending signals to the killer T cells from other cells via cell surface protein interactions and soluble mediators, such as cytokines. We have been studying killer T cells, which are missing a protein SOCS1. SOCS1 is important for switching off the signals generated by a group of cytokines. As a consequence of being unable to correctly regulate cytokine signals these killer T cells multiply inappropriately and contribute to disease development. Our current work is aimed at achieving a better understanding of the particular interactions between killer T cells and other immune system cells and the soluble factors that deliver important signals for maintaining killer T cells in the immune system. The ability to better understand the factors controlling the maintenance of killer T cells will enable us to more intelligently target the immune system ,which is important for improving vaccine strategies and cancer immunotherapy as well as for controlling T cells that are activated inappropriately, such as in autoimmune disease.Read moreRead less
Developmental Stages Of In Vivo And In Vitro-generated Dendritic Cell Subsets And Regulation Of T Cell Differentiation.
Funder
National Health and Medical Research Council
Funding Amount
$88,087.00
Summary
Dendritic cells (DC) represent a diverse family of white blood cells that form a sentinel network throughout the body involved in the detection and eradication of pathogens and cancer cells. DC can originate from different precursor cells in the bone marrow. It is therefore possible that different types of DC perform differing functions. For instance, DC not only initiate immune responses but are also able to silence them. However, the ability of DC to instruct and orchestrate the immune respons ....Dendritic cells (DC) represent a diverse family of white blood cells that form a sentinel network throughout the body involved in the detection and eradication of pathogens and cancer cells. DC can originate from different precursor cells in the bone marrow. It is therefore possible that different types of DC perform differing functions. For instance, DC not only initiate immune responses but are also able to silence them. However, the ability of DC to instruct and orchestrate the immune response may not only depend upon their origins but also on where they encounter pathogens or cancer cells and what other signals are associated with this encounter. Due to their specialized capacity to instruct the immune response (e.g. T cells, B cells and NK cells) of impending danger, DC are used experimentally to more efficiently deliver vaccines to the immune response so as to eradicate cancer or infectious disease. However, in order to successfully use DC to deliver vaccines, one must first understand how these cells normally behave in the body and what signals can alter their functional ability to orchestrate immune responses. We can generate DC outside the body from their precursors. We can also isolate DC from the circulation. This project seeks to identify how various physiologic stimuli differentially regulate the functional behaviour of DC subsets and how this then influences the DC's ability to instruct the developing T cell immune response. Furthermore, whether these signals are the same for DC generated outside the body with those isolated from the blood. Of particular interest is whether differing types of DC and differing stages of their maturity will differentially influence the T cell's ability to secrete immune response hormones and to recognize and kill cancer cells. The findings of this study have direct implications of how to best harness DC to effectively deliver vaccines and generate potent immune responses against cancer and infectious disease.Read moreRead less
Regulation Of Natural Killer Cell Homeostasis By Multiple Components Of The Immune System
Funder
National Health and Medical Research Council
Funding Amount
$327,151.00
Summary
Differentiation and homeostasis of immune cell populations such as CD4 and CD8 T cells and dendritic cells has been key to understanding their function during inflammation. In contrast, late stage natural killer (NK) cell differentiation has largely been ignored. Given the key role of NK cells in providing innate effector immunity and shaping adaptive responses, a better understanding of the cues that regulate their differentiation is clearly warranted.
Determinants Of Immune Restoration Disease And Persistent Immune Dysfunction In HIV Patients Responding To ART
Funder
National Health and Medical Research Council
Funding Amount
$445,011.00
Summary
Many people throughout the world now receive antiretroviral treatment (ART) for HIV-AIDS. ART increases numbers of CD4 T-cells, but does not restore all functions the immune system. In addition, some patients experience serious exacerbations of pre-existing secondary infections when they respond to ART. We were the first to describe these Immune Restoration Diseases and will investigate the underlying mechanisms and the causes of persistent immune deficiency here.
Influence Of TNF And TGF-beta On Langerhans Cell Mobilisation From Regressor And Progressor Skin Tumours
Funder
National Health and Medical Research Council
Funding Amount
$227,036.00
Summary
Skin cancer is the most common type of cancer in humans. It is caused by the ultraviolet wavelengths found in sunlight. Australia has the highest incidence of skin cancer in the world, due to the large amount of sun exposure experienced by Australians during work and leisure. Considerable research needs to be directed towards this disease to understand how it forms and how it can be treated. Skin cancer can be controlled by the immune system, which in some cases is able to destroy the cancer, so ....Skin cancer is the most common type of cancer in humans. It is caused by the ultraviolet wavelengths found in sunlight. Australia has the highest incidence of skin cancer in the world, due to the large amount of sun exposure experienced by Australians during work and leisure. Considerable research needs to be directed towards this disease to understand how it forms and how it can be treated. Skin cancer can be controlled by the immune system, which in some cases is able to destroy the cancer, so that it disappears, or regresses. Other skin tumours fail to be destroyed by the immune system and therefore grow progressively. Differences between progressor and regressor tumours can help define why the immune system is able to destroy some but not other tumours. The cell of the immune system that is responsible for initiating immune responses against skin cancer is called the Langerhans cell. This cell migrates between the cancer and the local lymph node, where it activates lymphocytes to leave the lymph node and destroy the cancer. Our studies have shown that a major difference between progressor and regressor skin tumours is the ability of Langerhans cells to migrate from these tumours. Skin tumours produce cytokines (hormone like molecules) which enhance or inhibit Langerhans cell mobilization from the tumour. We have identified some of the cytokines involved, and plan to study how these cytokines interfere with this process and whether they do this by increasing the production of other factors, or by having a direct influence on the Langerhans cells. This knowledge would increase our ability to utilize these cells for treatment of cancer. This study will also further basic understanding of the biological factors which regulate the movement of this important cell from our tissues to the draining lymph node, which is of fundamental importance in the development of immunity.Read moreRead less