The Impact Of Influenza A Virus PB1-F2 Protein On Host Immunity And The Potential For Therapeutic Targeting
Funder
National Health and Medical Research Council
Funding Amount
$317,076.00
Summary
The 1918 influenza virus pandemic resulted in 50 million deaths globally and there is potential for new pandemics, such as the predicted H5N1 Bird Flu . Exact causes of such devastating lethality are not fully identified. Newly discovered influenza A virus (IAV) PB1-F2 protein is present in nearly all highly pathogenic IAVs and promotes virus virulence. This study will further examine the way in which PB1-F2 impacts the host, revealing potential therapeutic targets to lessen disease burden.
Defining The Role Of Innate T Cells In The Onset And Progression Of Chronic Periodontitis
Funder
National Health and Medical Research Council
Funding Amount
$581,978.00
Summary
Particular immune cell populations (innate T cells), have a critical role in immunity. These cells are stimulated by bacterial cell wall components and are one of the first cells to appear after infection. We have shown that these innate T cells are stimulated by oral bacteria that cause the disease chronic periodontitis. This project will investigate how these innate T cells affect bacterial induced periodontitis and what role they play in disease outcomes.
IgA Mediated Activation Of FcalphaRI, An Fc Receptor And A Leukocyte Ig-like Receptor.
Funder
National Health and Medical Research Council
Funding Amount
$535,500.00
Summary
Our immune system exists to seek and destroy infections caused by bacteria and viruses (pathogens) that would grow in us. B cells in the immune system make antibody tags which attach to pathogens marking them for elimination. A special type of antibody is IgA. IgA occurs in two forms, the first is found at mucosal sites, these are membranous passages in the body, such as the lung, the gut and the genital tract. These communicate with the outside and are the major route of pathogen entry into the ....Our immune system exists to seek and destroy infections caused by bacteria and viruses (pathogens) that would grow in us. B cells in the immune system make antibody tags which attach to pathogens marking them for elimination. A special type of antibody is IgA. IgA occurs in two forms, the first is found at mucosal sites, these are membranous passages in the body, such as the lung, the gut and the genital tract. These communicate with the outside and are the major route of pathogen entry into the body. Here IgA forms a rather passive, but pathogen specific, sticky barrier to prevent microbial pathogens attaching to these large surfaces. In an everyday analogy this IgA behaves somewhat like fly-paper. This subdued response is appropriate as we are constantly exposed to micro-organisms living in our gut, or breathed into our lungs, and our immune system would make us ill if it aggressively attacked our innocuous microbial neighbours. The second type of IgA is found in the blood where it attaches to pathogens that have breached the body's barriers. These IgA tags are actively sought by white blood cells whose function is to protect the body from infection by recognising and engulfing the tagged pathogens and destroying them with killer molecules, including bleach. The IgA-Fc receptor is the sensor on the surface of white blood cells which seeks the IgA tags as they attach to pathogens. In order to survive in this hostile environment some of our pathogens, such as Staphylococcus, have their own strategies to make themselves invisible to the immune system. These strategies include cutting up the IgA tags or blocking the sensors for IgA. In this project we will study how IgA tags turn on white blood cells to destroy pathogens. We will also be looking at two Staphylococcal proteins which block up the sensor for IgA tags. Finally we are endeavouring to understand how it is the mucosal type IgA does not activate the white cells nearly as much as the IgA from the blood.Read moreRead less
Investigations Into The Mechanism Of Vaccine- Induced Protection Against The Gastric Pathogen Helicobacter Pylori.
Funder
National Health and Medical Research Council
Funding Amount
$276,000.00
Summary
Helicobacter pylori (H. pylori) is the most common gastro-intestinal pathogen worldwide and infects up to 20 % of the Australian population. Infection is thought to be acquired in childhood, and may cause acute or chronic gastritis, and gastric ulcer later in life. H. pylori infection is also strongly associated with the development of gastric cancer, the second most common cause of cancer death world- wide. In the long term a vaccine will be the best and most cost effective way to control this ....Helicobacter pylori (H. pylori) is the most common gastro-intestinal pathogen worldwide and infects up to 20 % of the Australian population. Infection is thought to be acquired in childhood, and may cause acute or chronic gastritis, and gastric ulcer later in life. H. pylori infection is also strongly associated with the development of gastric cancer, the second most common cause of cancer death world- wide. In the long term a vaccine will be the best and most cost effective way to control this disease. Vaccination against H. pylori is effective in laboratory animal models. A few vaccines have entered the early phases of clinical trials in human volunteers, however the results have been disappointing. We still do not understand how vaccination leads to killing of bacteria in the stomach, although it is known that antibodies are not responsible. A better understanding of how vaccination works in mice will help the design of vaccines for humans. In a novel approach to study vaccination, the gene expression pattern in the stomachs of immunized mice was analyzed using DNA micro-array technology. In this way we identified several novel genes, and as a result we have developed a new theory for how vaccination might lead to killing H. pylori. We propose that a combination of factors, act together to control H. pylori in the stomach: Leptin, known chiefly as the Obese gene, is a hormone produced by fat cells and controls appetite. Recently leptin has also been shown to influence immune cells (T- cells) in the stomach mucosa. These T-cells in turn send signals to the (epithelial) cells on the surface of the stomach which induces them to produce other proteins; some of which we believe may slow the fast-swimming H. pylori bacteria, and some small anti-microbial proteins (defensins), which are able to kill the bacteria directly by making holes in their membranes. The results of this research will be used to help design better H. pylori vaccines for humans.Read moreRead less
Understanding The Role Of MAIT Cells In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$547,593.00
Summary
A specialised set of T lymphocytes called Mucosal Associated Invariant T (MAIT) cells protect us from bacteria and yeast at mucosal sites where the body's immune defences are most easily breached, e.g. gut, oral cavity, airways & reproductive tract. This study investigates the role of MAIT cells in health and in diseases like inflammatory bowel disease, peptic ulceration, periodontitis and tuberculosis. Controlling MAIT cells could help in treating these conditions.
Acupuncture And Mucosal Immunity In The Upper Respiratory Tract
Funder
National Health and Medical Research Council
Funding Amount
$383,082.00
Summary
Many Australians seek complementary and alternate medicine for the treatment of allergic diseases such as allergic rhinitis. There is evidence that acupuncture treatment is clinically beneficial for the treatment of allergic rhinitis. This project will produce new information that will provide a scientific basis of how acupuncture influences the immune response and modulates inflammation. Broader application to other inflammatory diseases and therapeutic interventions is possible.
Coordinating Neuroimmune Sensory Networks In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$884,405.00
Summary
Living organisms use cellular rhythms to optimize their energy use and cellular responses. Our proposal aims to produce significant new fundamental knowledge by elucidating the fundamental cellular and molecular biology of innate cells, their role in mucosal homeostasis and tissue repair pathways in the gut. Understanding this foundational process of cellular regulation will generate new basic knowledge and may lead to better management systems.
Immune Regulation, Cellular Trafficking And Chemokine Receptors In Intestinal Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$204,750.00
Summary
The intestine is exposed to a vast array of foreign substances, or antigens, from food to the abundant bacteria that populate the gut. The gut immune system has developed elaborate and poorly understood mechanisms for preventing inflammation in response to these antigens. A breakdown in these control mechanisms may be partly responsible for the chronic intestinal diseases known as inflammatory bowel diseases, which cause abdominal pain, diarrhoea and bleeding. A recently described immune cell ty ....The intestine is exposed to a vast array of foreign substances, or antigens, from food to the abundant bacteria that populate the gut. The gut immune system has developed elaborate and poorly understood mechanisms for preventing inflammation in response to these antigens. A breakdown in these control mechanisms may be partly responsible for the chronic intestinal diseases known as inflammatory bowel diseases, which cause abdominal pain, diarrhoea and bleeding. A recently described immune cell type, known as a regulatory T cell (T reg), is a powerful candidate cell as a master controller of intestinal inflammation. We know that T cells move to various sites in the body under the influence of hormone-like proteins known as chemokines, but the existence of T reg cells in the intestine, their characteristics, their behaviour and their specific response to chemokines, are all unknown. These studies aim to examine the presence and nature of T reg cells in human and mouse intestine, in both health and inflammation, and to explore how these cells migrate into the gut under the influence of chemokines. This knowledge will help in our understanding of intestinal immunity and endogenous regulation of immune responses, and will provide new targets for treatment of inflammatory bowel disease, and potentially other inflammatory diseases.Read moreRead less
Development Of A Novel Mannan-based Avian Influenza Vaccine
Funder
National Health and Medical Research Council
Funding Amount
$195,566.00
Summary
We have a sugar (mannan) that can be used to increase immune responses. We have found that mannan decreases the dose of inactivated virus needed for intranasal immunization. We will investigate if dose sparing is seen when given intramuscularly. This method will be first tried with the human flu virus and if successful will be tried with the bird flu virus. If the preparation can protect mice and ferrets from human or bird flu infection it could develop into a human vaccine against bird flu.