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
The Study Of T Cell Differentiation And Function Using DNA Microarrays
Funder
National Health and Medical Research Council
Funding Amount
$155,665.00
Summary
The immune system uses specialized cells to combat various infectious agents, such as viruses or large parasites. The immune system remembers such pathogens, and is able to mount an enhanced and more rapid response upon secondary encounter. This property, termed immunological memory, is the basis of vaccination. Sometimes the normal functioning of the immune system goes awry, producing allergic disease (such as asthma) or autoimmune diseases (such as Multiple sclerosis and possibly rheumatoid ar ....The immune system uses specialized cells to combat various infectious agents, such as viruses or large parasites. The immune system remembers such pathogens, and is able to mount an enhanced and more rapid response upon secondary encounter. This property, termed immunological memory, is the basis of vaccination. Sometimes the normal functioning of the immune system goes awry, producing allergic disease (such as asthma) or autoimmune diseases (such as Multiple sclerosis and possibly rheumatoid arthritis). The nature of the cells that mediate immunological memory, or the processes that lead to inflammatory disease are poorly understood. A new approach towards understanding the function and inter-relationships of T cells is to use genomics techniques, that enable tens of thousands of genes to be assessed for their expression in different cells or tissues. An understanding of which genes are inappropriately turned on in different disease states should provide new understanding of disease process, and new targets for pharmaceutical intervention. We will systematically assess gene expression in various subsets of T cells, which have known functions. For instance Th1 cells have been implicated in the pathogenesis of autoimmune disease, and Th2 cells in the pathogenesis of asthma. How these cells regulate gene expression during their differentiation, and use their newly expressed genes for their specific functions is one aim of this study. Another important subdivision of the immune system is between skin homing and gut homing T cells. Gut homing T cells are thought to mediate protection in the gut against gut pathogens, but also to cause diseases such as inflammatory bowel disease (Ulcerative colitis, Crohn's disease). Finally, understanding which cells harbour immunological memory, and how this might be manipulated to improve immune resposes, is of great importance for vaccination programs.Read moreRead less
Regulation Of Perforin And Granzyme Expression In The Primary Cytolytic T Lymphocyte Response
Funder
National Health and Medical Research Council
Funding Amount
$756,000.00
Summary
The white blood cells known as cytolytic T lymphocytes (CTL) play important roles in elimination of some viruses, bacteria and tumours. Many vaccines and new therapies to prevent or control infections and cancer therefore seek to improve the production and activities of CTL. CTL kill infected cells and tumours by releasing packets of toxic molecules, including the pore-forming protein perforin and enzymes known as granzymes. However, while the roles of perforin and one granzyme, granzyme B, in c ....The white blood cells known as cytolytic T lymphocytes (CTL) play important roles in elimination of some viruses, bacteria and tumours. Many vaccines and new therapies to prevent or control infections and cancer therefore seek to improve the production and activities of CTL. CTL kill infected cells and tumours by releasing packets of toxic molecules, including the pore-forming protein perforin and enzymes known as granzymes. However, while the roles of perforin and one granzyme, granzyme B, in cell killing are now quite well understood, little is known about the other granzymes and how they contribute to immune protection. We have recently discovered that production of perforin and the three most prominent granzymes (A, B and C) can be separately controlled and that they are produced in different levels in different types of immune response. This suggests that they may each serve a different purpose and are therefore required in different amounts depending on the nature of the immune challenge. We have also found that an important hormone of the immune system, interleukin 4, has a profound effect on CTL, preventing their production of perforin and granzymes B and C and hence limiting their ability to kill target cells. In this project we plan a comprehensive analysis of perforin and granzyme production by CTL in response to different signals under controlled conditions in cell culture, and in response to different types of immune challenge in mice. We will also explore how interleukin 4 inhibits perforin and granzyme production and whether this has an impact on the effectiveness of the immune response. Mice in which one or more of the genes coding for perforin and granzymes has been damaged will be used to investigate how the absence of these molecules affects the immune response. We anticipate that these studies will suggest new strategies to improve therapeutic CTL induction by regulating perforin and granzyme production.Read moreRead less
Immunomodulatory Vaccines In The Treatment Of Peanut Allergy
Funder
National Health and Medical Research Council
Funding Amount
$678,899.00
Summary
Peanut allergy is the most common cause of food-induced anaphylactic reactions in Australia and is a major burden to our healthcare system. Current clinical practice advice dietary avoidance to prevent fatal anaphylactic responses. We propose the use of an immunomodulatory vaccine to re-write the immune response to peanut antigens, from an allergic to a tolerant phenotype. This study will provide novel insights into rational approaches for manipulating immune memory to food allergens.
Development Of Novel Vaccine Strategies To Prevent Genital Tract Chlamydial Infections
Funder
National Health and Medical Research Council
Funding Amount
$33,626.00
Summary
Chlamydia trachomatis is one of the most common sexually transmitted diseases in the developed world. Because an infection can remain undetected it can cause severe long term problems such as infertility. The aim of this project is to develop a successful vaccine using novel immunization regimes that not only protects from infection but also prevents the development of any long term problems.
Neonatal Immunization With Pneumococcal Conjugate Vaccine In Papua New Guinea
Funder
National Health and Medical Research Council
Funding Amount
$1,181,966.00
Summary
One million children die every year of pneumococcal (Pnc) disease, the majority in the third world. Many die in early infancy and babies may benefit from immunisation with a Pnc conjugate vaccine (PrevenarTM) at birth. The Papua New Guinea (PNG) Insatiate of Medical Research; Telethon Institute for Child Health Research and the Department of Paediatrics, University of Western Australia, will collaborate to closely examine the safety of this approach, particularly with regard to impact on the dev ....One million children die every year of pneumococcal (Pnc) disease, the majority in the third world. Many die in early infancy and babies may benefit from immunisation with a Pnc conjugate vaccine (PrevenarTM) at birth. The Papua New Guinea (PNG) Insatiate of Medical Research; Telethon Institute for Child Health Research and the Department of Paediatrics, University of Western Australia, will collaborate to closely examine the safety of this approach, particularly with regard to impact on the development of immunity and response to other vaccines given to infants. This study will also provide a unique opportunity for training of PNG and Australian scientists in both countries; transfer state-of-the-art immunological technology and stimulate further collaborations on respiratory infections in the region.Read moreRead less