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
The immune system plays an important role in protecting us from infectious diseases. To do this it regulates a series of cell types that must decide upon an appropriate course. In general, this response is successful and protective. However, occasionally the cells make an inappropriate decision leading to problems. For example, allergies are an incorrect response against pollens and dust mites. Similarly, autoimmune disease such as diabetes and multiple sclerosis result from inappropriate attack ....The immune system plays an important role in protecting us from infectious diseases. To do this it regulates a series of cell types that must decide upon an appropriate course. In general, this response is successful and protective. However, occasionally the cells make an inappropriate decision leading to problems. For example, allergies are an incorrect response against pollens and dust mites. Similarly, autoimmune disease such as diabetes and multiple sclerosis result from inappropriate attack upon our own tissues. Despite the clear importance of immune regulation for health, the complexity of its behaviour has made it difficult to predict and control. In this research program a new theory of immune regulation with clear implications for rational intervention and beneficial manipulation of the immune system will be developed.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
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
This project is based upon the observation that the mammalian immune system can distinguish between its own genetic material (DNA) and the DNA of infectious agents such as bacteria. This 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 how the recognition system for foreign DNA 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 DNA of infectious agents such as bacteria. This 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 how the recognition system for foreign DNA works. The cells that respond most vigorously to foreign DNA are large white blood cells called macrophages. We are investigating how a key protein that is required for these responses functions and what genes it turns on. 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
TSLP And Dysregulation Of Anti-viral Immunity In Atopic Dermatitis
Funder
National Health and Medical Research Council
Funding Amount
$504,097.00
Summary
Eczema (atopic dermatitis) is a frequent allergy in Australia. People with eczema can suffer very severe skin infections with some viruses, including the virus that causes cold sores, but we do not know why this happens. A newly discovered protein called TSLP is now known to be made by skin affected by eczema and there is evidence that TSLP may interfere with the way the body fights viruses. We will examine whether TSLP programs the immune system so that it is less able to fight viruses.
THE BIOLOGY OF HUMAN DEC-205: A POTENTIAL ANTIGEN LOADING RECEPTOR FOR DENDRITIC CELLS
Funder
National Health and Medical Research Council
Funding Amount
$227,017.00
Summary
Dendritic Cells (DC) represent a unique subset of white blood cells which play a critical role in initiating the immune response. Foreign material from bacteria-viruses and potentially cancer cells are recognised by DC, taken inside, processed and presented with other signals to T and B Lymphocytes for a response. Several DC surface molecules may beinvolved in the recognition of foreign material. We have cloned human DEC-205, a molecule which is predicted to bind the sugar groups associated with ....Dendritic Cells (DC) represent a unique subset of white blood cells which play a critical role in initiating the immune response. Foreign material from bacteria-viruses and potentially cancer cells are recognised by DC, taken inside, processed and presented with other signals to T and B Lymphocytes for a response. Several DC surface molecules may beinvolved in the recognition of foreign material. We have cloned human DEC-205, a molecule which is predicted to bind the sugar groups associated with bacteria-viruses and to act as a foreign material recognition and loading receptor. This project seeks to synthesise components of DEC-205 to test the binding capacities of its different components to different sugars and other molecules. We will also establish its expression pattern and how this is regulated on different white blood cell types. It is also possible that DEC-205 transmits signals which activate the DC, and we will test for that possibility. Finally, we will attempt to exploit this knowledge for loading cancer target molecules into DC via DEC-205 to initiate a cancer vaccine response.Read moreRead less
The Regulation And Differentiation Potential Of Human Memory B Lymphocytes
Funder
National Health and Medical Research Council
Funding Amount
$227,036.00
Summary
Antibody produced by our immune system plays a critical role in protecting us from infectious disease. Remarkably our ability to make antibodies is much faster the second time we see the infection. This memory of the previous attack occurs due to the formation of memory B cells that circulate in the blood, sometimes for years, looking for the same intruders. If they detect the infection they rapidly become activated and remake the antibody. These memory cells are very important for our protectio ....Antibody produced by our immune system plays a critical role in protecting us from infectious disease. Remarkably our ability to make antibodies is much faster the second time we see the infection. This memory of the previous attack occurs due to the formation of memory B cells that circulate in the blood, sometimes for years, looking for the same intruders. If they detect the infection they rapidly become activated and remake the antibody. These memory cells are very important for our protection. Vaccines operate by tricking the immune system into making these memory cells, even though the body hasn't seen the actual disease. Although clearly vital for our health little is known about the activation and antibody production by human B memory cells. This project will redress our lack of knowledge by performing a comprehensive evaluation of the properties of this important cell type.Read moreRead less