Exploring The Contribution Of The Immunoproteasome To Immunodominance And T Cell Function
Funder
National Health and Medical Research Council
Funding Amount
$82,421.00
Summary
The immunoproteasome is a piece of cellular machinery which degrades proteins and has been shown to enhance the body's recognition and response to viruses and cancer cells. This immunoproteasome is made up of various subunits, but it has not yet been assessed how each of these subunits contribute to the overall response. By studying the individual subunits, we will have a better understanding in how to manipulate the immune system for anti-viral and anti-cancer vaccine design.
Tracking Endogenous Presentation Of MHC Class-II-Restricted Viral Epitopes
Funder
National Health and Medical Research Council
Funding Amount
$165,436.00
Summary
CD4+ T cells play an important role in controlling viral infections. Proteins from viruses are processed into small pieces by immune stimulating cells and these are then displayed on special molecules of the immune stimulating cells for the CD4+ T cells to recognise and respond to. This project aims to establish the various pathways by which the immune stimulating cells process the proteins and present them to the CD4+ T cells.
Functional Suicide Of Selected Dendritic Cells By Cytochrome C: An In Vivo Model Lacking Cross-presentation
Funder
National Health and Medical Research Council
Funding Amount
$597,476.00
Summary
Certain white blood cells (dendritic cells) activate the immune system, especially its T cells. Infection of such cells elicits killer T cell responses. However not all infections infect dendritic cells. In such cases, the infectious material is eaten by dendritic cells and moved to certain areas within the cell. This process is called cross-presentation and how important it is during various diseases remains moot. We now have a model of testing this by eliminating these cross-presenting cells.
The Genetics Controlling The Course Of Herpesvirus Infection In Humans
Funder
National Health and Medical Research Council
Funding Amount
$69,684.00
Summary
Epstein-Barr Virus and Human Cytomegalovirus are common viruses present in more than 50% of the adult population. They have a major impact on the human immune system, stimulating large numbers of T cells that are essential to control the persistent viral infection. Generally, these viruses cause few problems; however, an unfortunate minority suffer major life threatening clinical problems. There has also been some evidence for a role of EBV infection in the pathogenesis of Multiple Sclerosis.
Mechanisms Regulating Antigen Presentation During Primary And Recall Responses Of T Cells Following Pathogen Infection
Funder
National Health and Medical Research Council
Funding Amount
$441,364.00
Summary
The primary role of the immune system is the containment of pathogens, cancer cells and infections. This depends on generating long-lived memory CD8+ killer T lymphocytes. Generally this process is achieved efficiently in acute infections in which the pathogen grows relatively rapidly. However, pathogens such as herpes viruses and tuberculosis grow more slowly, fail to efficiently activate the killer T cells such that they elude the immune system and are never completely removed from the body. T ....The primary role of the immune system is the containment of pathogens, cancer cells and infections. This depends on generating long-lived memory CD8+ killer T lymphocytes. Generally this process is achieved efficiently in acute infections in which the pathogen grows relatively rapidly. However, pathogens such as herpes viruses and tuberculosis grow more slowly, fail to efficiently activate the killer T cells such that they elude the immune system and are never completely removed from the body. These latter infections result in persistent or chronic infections. Our work will endeavour to unravel the mechanisms that underlie how a killer T cell is effectively activated and the factors that contribute to failure of these cells to be similarly activated in a persistent infection. The central aim of the studies described in this proposal is to understand the mechanisms utilized by different pathogens to generate the diverse population of memory killer T cells that allow us to respond to the plethora of pathogens we might encounter every day. These studies will improve our understanding of how antigen presenting cells and killer T lymphocytes ensure an immune response is maintained and may identify checkpoints that could be targeted to modulate the immune response when it goes wrong.Read moreRead less
Investigation Into The Immunogenicity Of Dendritic Cell-derived Exosomes
Funder
National Health and Medical Research Council
Funding Amount
$257,036.00
Summary
Dendritic cells are essential in immune responses. They have unique capacity to stimulate lymphocytes specific to viruses, bacteria and cancers. They are extremely rare and difficult to isolate. We have developed a method of culture which gives a continuous supply of dendritic cells. Cells produced in our culture also produce a high yield of acellular membranous particles called 'exosomes' which have been previously been very difficult to isolate and characterise. Some preliminary reports sugges ....Dendritic cells are essential in immune responses. They have unique capacity to stimulate lymphocytes specific to viruses, bacteria and cancers. They are extremely rare and difficult to isolate. We have developed a method of culture which gives a continuous supply of dendritic cells. Cells produced in our culture also produce a high yield of acellular membranous particles called 'exosomes' which have been previously been very difficult to isolate and characterise. Some preliminary reports suggest that exosomes can induce or modify immune responses and that they have enormous immunotherapeutic potential. Further study of their clinical application is limited by the difficulty of isolating enough dendritic cells from which to isolate exosomes. This study will involve production and characterisation of exosomes from our unique murine dendritic cell culture system. Exosomes isolated will be assessed in terms of potential for immunotherapeutic treatment of disease such as cancer, viral infection and autoimmunity.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