MAIT cells are a recently discovered type of lymphocyte that plays a unique and important role in the immune system. However, these cells vary widely in number between healthy individuals, for reasons that are unclear. This project is designed to understand the factors that control the development of MAIT cells as a step toward regulating their numbers and activity.
Vaccines that deposit memory T cells within the lung, gut and genital tract hold enormous therapeutic potential, as these mucosal surfaces are major portals of entry into the body for many viruses. However, the accumulation of large numbers of T cells within the mucosal tissue may increase the number of target cells for T cell trophic viruses (eg HIV) to infect. We will explore factors that result in the generation of mucosal memory T cells that are resistant to virus infection.
Characterization Of MAIT Cell Function And Frequency At The Rectal Mucosa And Gastrointestinal Tract During HIV/SIV Infection
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
This project focuses on determining how HIV infection alters the function of rare, unconventional immune cell populations in the gastrointestinal tract. These cells are not well described in humans or primate models of HIV infection, but we will determine whether these cells are depleted by HIV infection and whether there are interventions that can boost the function of these cells in order better fight HIV infection.
Long Lived, Virus Resistant Resident Memory T Cells
Funder
National Health and Medical Research Council
Funding Amount
$415,218.00
Summary
Vaccines that deposit memory T cells within the lung, gut and genital tract hold enormous therapeutic potential, as these mucosal surfaces are major portals of entry into the body for many viruses. However, the accumulation of large numbers of T cells within the mucosal tissue may increase the number of target cells for T cell trophic viruses (eg HIV) to infect. We will explore factors that are important in the generation of mucosal memory T cells that are also resistant to virus infection.
Cellular And Molecular Pathways Regulating Airway Mucosal Dendritic Cells During Onset Of Allergic Airways Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$491,065.00
Summary
Allergic airways inflammation (AAI), which leads to debilitating disease such as allergic asthma, is a condition medaited by the abnormal activity of the immune system towards essentially harmless inhlaed allergens. Two special cell types of the immmune system that are important in controlloing the onset and persistence of AAI are known as dendritic cells (DC) and T helper type 2 cells (Th2 cells). DC are located in all parts of the respiratory tract and are important in providing control signal ....Allergic airways inflammation (AAI), which leads to debilitating disease such as allergic asthma, is a condition medaited by the abnormal activity of the immune system towards essentially harmless inhlaed allergens. Two special cell types of the immmune system that are important in controlloing the onset and persistence of AAI are known as dendritic cells (DC) and T helper type 2 cells (Th2 cells). DC are located in all parts of the respiratory tract and are important in providing control signals to Th2 cells to become switched on and start to react to an inhaled allergen. Th2 cells then generate a variety of signals that initiate an cascade of immune responses towards the allergen that ultimately can lead to AAI and asthma if left unchecked, however this process remians relatively poorly understood. This project aims to examine how DC and Th2 interact, and at what level DC activity can be regulated so that unchecked Th2 immunity to harmless inhaled allergens can be controlled. The hope is to be able to identify new cellular and molecular pathways that can eventually become the target for new generations of preventative and therapeutic drugs.Read moreRead less
Understanding And Improving The Non-human Primate Model For Human Immunodeficiency Virus Vaccine-induced Mucosal Immunity.
Funder
National Health and Medical Research Council
Funding Amount
$302,123.00
Summary
The overall aim of this project if to generate a more effective vaccination for HIV, using an animal model of the disease. We will test vaccination methods targeting immunity to the reproductive tract, in order to attack the virus where it is usually first encountered.
A specialised set of T lymphocytes called Mucosal Associated Invariant T (MAIT) cells react against bacteria and yeast, and reside at mucosal sites where the body's immune defences are most easily breached, e.g. respiratory tract and intestinal mucosa. This study investigates the role of MAIT cells in both protection and pathology in bacterial infections. Controlling MAIT cells could help in treating these conditions.
Unrestricted antigen recognition by T lymphocytes. This project aims to investigate the unrestricted T cell repertoire; the molecular and structural basis of antigen recognition by unrestricted T cells; and the development of unrestricted T cells. T lymphocytes typically are restricted to detecting foreign molecules (antigens) on the cell membrane in association with specialised antigen-presenting molecules encoded within the highly polymorphic major histocompatibility (MHC) locus (MHC restricti ....Unrestricted antigen recognition by T lymphocytes. This project aims to investigate the unrestricted T cell repertoire; the molecular and structural basis of antigen recognition by unrestricted T cells; and the development of unrestricted T cells. T lymphocytes typically are restricted to detecting foreign molecules (antigens) on the cell membrane in association with specialised antigen-presenting molecules encoded within the highly polymorphic major histocompatibility (MHC) locus (MHC restriction). T lymphocytes that can recognise antigens in the absence of MHC or MHC like molecules challenges a major paradigm in the field of immunology. As T cell based therapy underpins treatments for cancer and infection, new mechanisms of T cell activation that are independent of patient genotype should ultimately create opportunities for therapeutic and commercial development, leading to both health and economic benefits.Read moreRead less
CD1C-LIPID-REACTIVE T CELLS. The immune system patrols our body examining molecules such as proteins and lipids that signal whether or not everything is ok. While protein recognition by the immune system is well understood, our knowledge of the fundamental features of lipid detection is poor. This project will investigate the detection of lipid molecules that are presented to the immune system in association with a molecule known as CD1c. The aims are to understand: 1. The cells that respond to ....CD1C-LIPID-REACTIVE T CELLS. The immune system patrols our body examining molecules such as proteins and lipids that signal whether or not everything is ok. While protein recognition by the immune system is well understood, our knowledge of the fundamental features of lipid detection is poor. This project will investigate the detection of lipid molecules that are presented to the immune system in association with a molecule known as CD1c. The aims are to understand: 1. The cells that respond to these lipids; 2. The cellular receptors that bind to these lipids; 3. The types of lipids involved in this process. This work is essential for us to understand lipid-based immunology which is critical if we ultimately wish to harness this to improve human health.Read moreRead less
Understanding immune mechanisms induced by pulmonary vaccination. This project aims to better understand the mechanisms of immune induction of a novel lung vaccination strategy. The ability to deliver vaccines that induce potent lung and body wide immune responses in a safe and efficient manner has wide implications for both human and animal health. Ultimately, the vaccine will be delivered to the lung as stable dry powders in an attempt to negate the need for a transport cold chain and therefor ....Understanding immune mechanisms induced by pulmonary vaccination. This project aims to better understand the mechanisms of immune induction of a novel lung vaccination strategy. The ability to deliver vaccines that induce potent lung and body wide immune responses in a safe and efficient manner has wide implications for both human and animal health. Ultimately, the vaccine will be delivered to the lung as stable dry powders in an attempt to negate the need for a transport cold chain and therefore facilitate the distribution of the vaccines to remote areas. The project will not only benefit the Australian biotechnology industry but also the community at large and in particular those in remote areas without access to modern medical facilities.Read moreRead less