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
Contribution Of Dendritic Cell Paralysis To The Immunosuppression Associated With Systemic Infections
Funder
National Health and Medical Research Council
Funding Amount
$490,051.00
Summary
The immune system fights viruses and other infections mobilising antibody-producing B cells and killer T cells. The B cells and killer T cells are recruited by specialysed cell of the immune system called Dendritic Cells (DC). The DC are distributed all over the body, where they play an immunosurveillance role: they constantly monitor their sorroundings for the presence of pathogens. When DC detect these pathogens they become activated . They capture the pathogen, break it into small pieces call ....The immune system fights viruses and other infections mobilising antibody-producing B cells and killer T cells. The B cells and killer T cells are recruited by specialysed cell of the immune system called Dendritic Cells (DC). The DC are distributed all over the body, where they play an immunosurveillance role: they constantly monitor their sorroundings for the presence of pathogens. When DC detect these pathogens they become activated . They capture the pathogen, break it into small pieces called antigens, and display these antigens on their surface, where they can be seen by helper T cells, which in turn mobilise the B cells, and by killer T cells. This chain of reactions initiates an immune response. The DC undergo profound changes after they detect pathogens. They stop monitoring their sorroundings, and concentrate on displaying to T cells the antigens that belonged to the pathogen that triggered their initial activation. Indeed, they do not respond to new pathogen encounters. In normal conditions few DC are activated by each pathogen encounter, so there are always enough DC ready to respond to new infections. However, there are situation that activate nearly all the DC at the same time. This can happen during sepsis (bacterial infection of the blood) and malaria. It has been recognised for a long time that these two conditions can be immunosuppressive they shut-down the immune system. Our previous work has demonstrated that this is in part due to the excessive number of DC that sepsis or malaria activate, leaving no more DC capable of responding to subsequent infections. This work has focused on the immediate effects of sepsis or malaria -within the first 24 hours or so; now we want to investigate the efffect of these conditions on the reconstitution of the DC network. We think this will help us to find treatments to restore immunocompetence a functional immune system- in sepsis or malaria patients.Read moreRead less
Regulation Of Monocyte And Macrophage Functions By Leucocyte Immunoglobulin-like Receptors (LILRs) In Human Colon
Funder
National Health and Medical Research Council
Funding Amount
$295,983.00
Summary
The human colon contains many bacteria that can invade through a damaged mucosal barrier and provoke immune cells to cause inflammation with their subsequent removal and a rapid shutdown of inflammation. Failure to clear bacteria or inflammation can lead to inflammatory bowel disease or sepsis. We will investigate how new proteins known as Leucocyte Immunoglobulin-like Receptors allow immune cells to effectively clear microorganisms without provoking uncontrolled inflammation