Real-time imaging of the initiation of adaptive immunity in vivo. Understanding the first few hours of an immune response is fundamental to understanding how the human immune system functions. The immune system mounts our responses to infectious diseases, but can also cause autoimmune disease, allergy, and organ graft rejection. We will study how naive antigen-specific T cells first contact antigen in lymph nodes using 2-photon intravital microscopy. The research has the potential to change the ....Real-time imaging of the initiation of adaptive immunity in vivo. Understanding the first few hours of an immune response is fundamental to understanding how the human immune system functions. The immune system mounts our responses to infectious diseases, but can also cause autoimmune disease, allergy, and organ graft rejection. We will study how naive antigen-specific T cells first contact antigen in lymph nodes using 2-photon intravital microscopy. The research has the potential to change the way we think about the clonal selection of lymphocytes, the fundamental theory underlying our understanding of the immune system.Read moreRead less
Mechanism of action of an anti-inflammatory compound which targets alternatively activated macrophages. The project will study the mechanism by which a novel anti-inflammatory compound, developed by our commercial partner, suppresses the activity of a population of cells known as alternatively activated macrophages. These cells play a key role in driving allergic inflammation, including the inflammation associated with asthma.
Development of microbial bioproducts for the suppression of inflammation. Asthma and inflammatory diseases are serious health problems that result from excessive inflammation. Exposure to bacteria may reduce inflammation. This project will identify the bacterial components that reduce inflammation and develop them into new anti-inflammatory therapies for asthma.
Molecular determinants of an allergic response. Some humans develop allergies after exposure to environmental allergens while others do not. At present, the reason for this individual variation is not known. By comparing the processes activated in allergic versus non-allergic individuals, this study will identify critical molecules involved in making individuals susceptible to allergies, which will be used to develop safer and more effective allergy vaccines.
Dissecting the Parameters for the Generation of Cytotoxic T Lymphocyte Immunity. This project aims to identify mechanisms by which antigen-presenting cells, such as dendritic cells, prime CD8+ T cells to generate effector and memory populations at the molecular level. The specific intention is to identify reagents capable of licensing dendritic cells, and examine the down-stream gene products/pathways generated by these signals using microarray analyses. Such knowledge will provide new insight i ....Dissecting the Parameters for the Generation of Cytotoxic T Lymphocyte Immunity. This project aims to identify mechanisms by which antigen-presenting cells, such as dendritic cells, prime CD8+ T cells to generate effector and memory populations at the molecular level. The specific intention is to identify reagents capable of licensing dendritic cells, and examine the down-stream gene products/pathways generated by these signals using microarray analyses. Such knowledge will provide new insight into CTL generation by providing greater understanding of how multicellular systems function both at the cellular and molecular level.Read moreRead less
Imaging of immune responses to pathogens in vivo. This proposal represents an excellent opportunity for Australian science to participate in state-of-the-art research into the immune system and to be internationally competitive with the best researchers in the field. By combining advanced microscopy techniques with well developed biological models used by researchers at the University of Melbourne, this project will greatly improve our understanding of the dynamic interactions that occur betwee ....Imaging of immune responses to pathogens in vivo. This proposal represents an excellent opportunity for Australian science to participate in state-of-the-art research into the immune system and to be internationally competitive with the best researchers in the field. By combining advanced microscopy techniques with well developed biological models used by researchers at the University of Melbourne, this project will greatly improve our understanding of the dynamic interactions that occur between cells of the immune system during infectious diseases. The insight provided by this project will facilitate the design of better vaccines for protection against diseases, including influenza.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
CD4 T cell programming by neonatal and early-life infection. T lymphocytes (T cells) are white blood cells that play a critical role in protecting the body from infection. Before T cells can function they need to be programmed so that they can specifically respond to an infectious agent (a type of bacteria or virus). Inappropriate programming can lead to disease. Whether T cells respond to an infectious agent or foreign substance in a protective or destructive manner may critically depend on the ....CD4 T cell programming by neonatal and early-life infection. T lymphocytes (T cells) are white blood cells that play a critical role in protecting the body from infection. Before T cells can function they need to be programmed so that they can specifically respond to an infectious agent (a type of bacteria or virus). Inappropriate programming can lead to disease. Whether T cells respond to an infectious agent or foreign substance in a protective or destructive manner may critically depend on the age that an individual first encounters the infection. Our project will identify critical periods in life that direct T cell programming to subsequent protective or destructive responses, providing new insights into the developing immune system that may be exploited to treat disease or develop vaccines.Read moreRead less
Regulation Of T-cell Activation In The Airway Mucosa Of Rats Expressing Low Versus High IgE Responder Phenotype
Funder
National Health and Medical Research Council
Funding Amount
$713,058.00
Summary
We have established an experimental rat model of allergic airways inflammation which mimics human asthma. Interactions occurring between airway mucosal dendritic cells and CD4+ Th2 (effector) cell populations are responsible for the late phase response (LPR) component of asthma exacerbations, including airways hyperresponsiveness (AHR). We have previously demonstrated that termination of the LPR and prevention of its continual recurrence in the face of ongoing aeroallergen challenge is establish ....We have established an experimental rat model of allergic airways inflammation which mimics human asthma. Interactions occurring between airway mucosal dendritic cells and CD4+ Th2 (effector) cell populations are responsible for the late phase response (LPR) component of asthma exacerbations, including airways hyperresponsiveness (AHR). We have previously demonstrated that termination of the LPR and prevention of its continual recurrence in the face of ongoing aeroallergen challenge is established via the induction of a state of dynamic equilibrium, mediated by local T regulatory cells (Treg) which act to functionally silence local Th2 memory (effector) cells. Maintenance of protective Treg activity is dependent upon continuing allergen exposure as cessation of exposure leads to waning of Treg numbers and function and release of mucosal allergen specific Th2 cells from control. These studies have primarily involved low IgE responder (LR) PVG rats (normals or nonatopics). The present study will focus on elucidating the control of Th2 dependent immune responses to inhaled antigen in high IgE responder (HR) BN rats (atopics). Studying these two strains in parallel enables a comparison between the extremes of the spectrum of susceptibility to both the induction and the expression of Th2 immunity in the airways. A more detailed understanding of the cellular interactions occurring within the airway mucosa and draining lymph nodes and the mechanisms responsible for the maintenance of immunological homeostasis within the airways will provide new insights into the pathogenesis of inflammatory airway diseases such as atopic asthma. This will enable further development and possibly illuminate other avenues of intervention for more effective therapeutic strategies used in the control of asthma, which is the long term goal of this research.Read moreRead less
Understanding T cell immunity induced by infection. We aim to understand how killer T cells are “programmed” upon activation and acquire their characteristic functions and how these are maintained into immunological memory. This proposal will provide insights important for the design and improvement of vaccine strategies to fight pathogens such as influenza, HIV and even tumors.