Structural Investigations Of Bacterial Evasion Of IgA Mucosal And Systemic Immunity
Funder
National Health and Medical Research Council
Funding Amount
$488,812.00
Summary
Nose, throat and skin infections are often caused by streptococcal and staphylococcal bacteria, known as Strep Throat and Golden Staph. Infections can be life-threatening in newborns, the elderly or individuals with weak immune systems. These bacteria make proteins bind and inactivate immune proteins. Our research examines the structural basis for bacterial interactions with a key immune system protein (an antibody called IgA) and may lead to new prevention and treatment strategies.
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
Fc Alpha RI: Ligand Interaction And Membrane Organisation.
Funder
National Health and Medical Research Council
Funding Amount
$497,640.00
Summary
Antibodies tag invading viruses or bacteria thus marking them as foreign and targeting them for destruction by the immune system. In man the most prevelant antibody is IgA and this antibody provides protection from infecton in the blood and in the fluids at the surface of the lungs, gut and urinogenital tract. Once tagged by antibody the invading bacteria or antigen can be recogniseed white blood cells. These workhorses of the immune system use special molecules called Fc receptors on their surf ....Antibodies tag invading viruses or bacteria thus marking them as foreign and targeting them for destruction by the immune system. In man the most prevelant antibody is IgA and this antibody provides protection from infecton in the blood and in the fluids at the surface of the lungs, gut and urinogenital tract. Once tagged by antibody the invading bacteria or antigen can be recogniseed white blood cells. These workhorses of the immune system use special molecules called Fc receptors on their surface to recognise antibody tags. The receptor for IgA tags is called the Fc alpha receptor. This receptor is essential for the normal IgA-mediated protection against infection. However in a common kidney disease IgA tags accumulate in the glomerulus of the kidney stimulating white blood cells to attack and damage the kidney. This study will explain how the Fc alpha receptor recognises IgA antibody tags. It will investigate how the presentation of different forms of the receptor and different types of IgA antibody tags contributes to immunity to infection. For example one form of the receptor has a fat molecule joined to its end. We believe this may affect where the Fc alpha recptor goes to in the white blood cell membrane and whether it can activate the white blood cell to fight the invading microorganism.Read moreRead less