CTL Avidity As A Determinant Of The Mature, Antigen-specific Immune Repertoire
Funder
National Health and Medical Research Council
Funding Amount
$241,527.00
Summary
Killer T lymphocytes are a diverse population which vary in their ability to recognise infected cells. This study aims to determine whether vaccine dose and frequency impact on the generation of highly sensitive killer T cells. This study will improve our basic knowledge of killer T lymphocyte selection during infection and have application to improved methods of vaccination.
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 Macrophage Function And Gene Expression By The Th2-Promoting Stimulus, ES-62
Funder
National Health and Medical Research Council
Funding Amount
$465,750.00
Summary
White blood cells are responsible for co-ordinating the immune response against foreign micro-organisms. Macrophages are a particular type of white blood cell that attempt to destroy microbes during the initial stages of an infection, but also release toxic substances that are responsible for pathology and side effects during many immune responses. This project aims to address how macrophages are involved in a particular type of immune response that develops when individuals are susceptible to c ....White blood cells are responsible for co-ordinating the immune response against foreign micro-organisms. Macrophages are a particular type of white blood cell that attempt to destroy microbes during the initial stages of an infection, but also release toxic substances that are responsible for pathology and side effects during many immune responses. This project aims to address how macrophages are involved in a particular type of immune response that develops when individuals are susceptible to certain diseases including asthma and diseases associated with intracellular infections. We are identifying genes expressed in macrophages during these immune responses that are likely to be involved in susceptibility to such diseases.Read moreRead less
Investigation Of Dendritic Cell Activation And Function In A Murine Model Of Plasmodium And Schistosoma Co-infection
Funder
National Health and Medical Research Council
Funding Amount
$358,938.00
Summary
Malaria is responsible for over 2 million deaths annually, mainly in sub-Saharan Africa. Importantly, around 1 billion people in malaria endemic areas are infected with parasitic worms, thus malaria and worm co-infections frequently occur. This project will investigate how malaria and worm parasites interact to influence the immune response and clinical outcomes of each other in a mouse infection model. This will provide new strategies for the design of effective treatments in co-endemic areas.
Regulation Of Macrophage Gene Expression And Function By Histone Deacetylases
Funder
National Health and Medical Research Council
Funding Amount
$35,909.00
Summary
Macrophages are white blood cells that play a major role in the development of inflammatory diseases such as rheumatoid arthritis and atherosclerosis, diseases that are a major burden to Australian society. This project aims to characterise the effects of a novel class of potential anti-inflammatory agents on macrophages. Defining how these drugs modify macrophages in disease models will allow design of therapeutics with minimal side effects.
Role Of The Mast Cell Product Histamine In Ultraviolet Radiation Induced Systemic Immunomodulation
Funder
National Health and Medical Research Council
Funding Amount
$393,750.00
Summary
The harmful effects of ultraviolet radiation on skin, as exemplified by sun exposure, are well recognised: sunburn, premature ageing of skin, and induction of skin cancer. Indeed, skin cancers are the most common cancers in Australia. Increasingly recognised now is that UV radiation can alter the immune system. This is of particular relevance to the development of skin cancer: alteration of the immune system is critical to outgrowth of UV-induced cancers. The intact immune system is otherwise ab ....The harmful effects of ultraviolet radiation on skin, as exemplified by sun exposure, are well recognised: sunburn, premature ageing of skin, and induction of skin cancer. Indeed, skin cancers are the most common cancers in Australia. Increasingly recognised now is that UV radiation can alter the immune system. This is of particular relevance to the development of skin cancer: alteration of the immune system is critical to outgrowth of UV-induced cancers. The intact immune system is otherwise able to reject the great majority of UV-induced skin cancers. This effect of UV radiation on the immune system may be relevant to other diseases. It may alter the course of some infections, change the way the body responds to vaccination, and may also have a role in some immune-related diseases such as multiple sclerosis. How it is that these wavelengths just beyond visible light can affect the immune system is the subject of this project. We know that UV radiation can penetrate only a short way into the skin, yet can have widespread effects on the immune system. Our research to now has shown that a particular cell type sitting just below the surface of skin, the dermal mast cell, is essential. We've also demonstrated some of the complexity of the early response to UV exposure - both a chemical (cis-urocanic acid) in the very outermost layer of skin, and nerves in the skin, have roles. Importantly, anti-histamines can inhibit UV effects on immune responses. Additional lines of evidence also point to histamine, a product of mast cells, as playing a pivotal role in the immune alterations following UV exposure. Our research aims to characterise the effects of histamine on cells central to the development of immune responses, known as dendritic cells, and define the mechanisms of the effect in experimental models. In collaboration with researchers in the UK, we will further characterise the role of mast cells in UV alterations to immunity in humans.Read moreRead less
Cellular And Molecular Events During Antigen Dependent B Cell Differentiation
Funder
National Health and Medical Research Council
Funding Amount
$283,329.00
Summary
The immune system is essential for protecting us against invasion from without by viruses and bacteria and invasion from within by cancer cells. Among the white blood cells making up this system are those responsible for producing antibodies. To ensure that all possible infections and tumours can be recognised, the body needs to manufacture a very large number of these cells on a continuous basis. The aim of this project is to work out the mechanism responsible for controlling their production a ....The immune system is essential for protecting us against invasion from without by viruses and bacteria and invasion from within by cancer cells. Among the white blood cells making up this system are those responsible for producing antibodies. To ensure that all possible infections and tumours can be recognised, the body needs to manufacture a very large number of these cells on a continuous basis. The aim of this project is to work out the mechanism responsible for controlling their production and function using a novel experimental system. By pinpointing the different stages involved in antibody production in the normal host we should be in a better position to make longer lasting vaccines in the future and to understand what goes wrong with these white cells in disease. In particular, the results should shed light on the chronic form of leukaemia called myeloma and some of the autoimmune disorders like the rheumatic diseases which occur when the antibodies being produced attack our own tissues.Read moreRead less
Mechanisms Of Macrophage Activation By Immunostimulatory DNA
Funder
National Health and Medical Research Council
Funding Amount
$230,728.00
Summary
This project is based upon the observation that the mammalian immune system can distinguish between its own genetic material (DNA) and the genes of infectious agents such as bacteria. This fact has implications for understanding how the immune system copes with infection, and also for design of new therapies and vaccines. Our central aim is to define exactly how this recognition system works. The cells that respond most vigorously to foreign DNA are large white blood cells called macrophages. We ....This project is based upon the observation that the mammalian immune system can distinguish between its own genetic material (DNA) and the genes of infectious agents such as bacteria. This fact has implications for understanding how the immune system copes with infection, and also for design of new therapies and vaccines. Our central aim is to define exactly how this recognition system works. The cells that respond most vigorously to foreign DNA are large white blood cells called macrophages. We aim to find the macrophage protein which binds to foreign DNA and triggers the activation of the immune system. The type of immune responses initiated by foreign DNA may be useful in treatment of allergies and cancer and for improving vaccinations.Read moreRead less