The Quantitative Regulation Of Antibody Forming Cell Differentiation
Funder
National Health and Medical Research Council
Funding Amount
$336,500.00
Summary
B lymphocytes are the antibody-producing cells of the immune system. After they are made in the bone marrow, they are exported to the body to circulate, searching for signs of infection. When they encounter an invader, they change, with the help of other immune cells, into antibody-producing cells. A small proportion of the cells are set aside as memory cells that can rapidly become antibody-producing cells should the same infection occur again in the future. This is the basis of vaccination. Th ....B lymphocytes are the antibody-producing cells of the immune system. After they are made in the bone marrow, they are exported to the body to circulate, searching for signs of infection. When they encounter an invader, they change, with the help of other immune cells, into antibody-producing cells. A small proportion of the cells are set aside as memory cells that can rapidly become antibody-producing cells should the same infection occur again in the future. This is the basis of vaccination. The secretion into serum of antibodies that can bind to and eliminate an invader anywhere in the body is the main function of B lymphocytes. This project studies how a B cell changes into an antibody-producing cell. We will learn very basic and detailed quantitative aspects of the process, such as: -How long does it take to become an antibody-producer once a B cell detects an invader? -Do they-must they divide while they are changing? -How do hormones from other cells regulate the process? Do they increase division, survival, change the properties of the B cells, or improve their output? We will study all these responses in detail, so that we can make a model that can accurately predict the outcome of a particular set of circumstances. We will study the genes that are known to be required for antibody-producing cells to form, or to do their work. We will also study animals whose immune systems are under- or over-active, to find out what part of the antibody-producing process is faulty. We may be able to predict where the problem lies, by comparing these animals cells to our model, and therefore to suggest a remedy. Using this information, we hope eventually to be able to study diseases of antibody producing cells in humans (as occur in allergy, asthma, rheumatoid arthritis and leukaemia), to be able to identify the precise cause of the problem, and to suggest a therapy. This information may also be used to improve the outcome of vaccination.Read moreRead less
Investigating The Role Of TCR Avidity In Influenza Virus-specific CD8 T Cell Responses
Funder
National Health and Medical Research Council
Funding Amount
$83,142.00
Summary
One of the constituents of the immune system is the cytotoxic, or killer, T cells and these are important in the overall protection from viral infection. Activation of these T cells is mediated by signalling through the T cell receptor (TCR). This study will definitively determine how the strength with which the TCR binds to the activating ligand, can influence the quality of virus-specific T cell immune responses after infection. This has implications for vaccine design.
Immune Correlates Of Protection Against HCV - A Potential Role For NK Cells And NKR Expression On T Lymphocytes
Funder
National Health and Medical Research Council
Funding Amount
$72,754.00
Summary
Hepatitis C virus (HCV) poses a major public health problem with ~200 million people infected worldwide and no available vaccine. Injecting drug users (IDUs) are the major risk group, with 75% of infected individuals progress to chronic infection, which can then lead to liver cirrhosis and hepatocellular carcinoma. However, about 20% of a given cohort of IDUs remains uninfected. This project is therefore focused on understanding the innate immune mechanisms behind this protection.
Defining The Role Of Lymphotoxin Alpha In Experimental Cerebral Malaria
Funder
National Health and Medical Research Council
Funding Amount
$158,250.00
Summary
Malaria kills millions of children every year. A major cause of death is cerebral malaria (CM) resulting from Plasmodium falciparum infection. At present, there is no effective vaccine available and drug-resistant parasites are widespread. CM is a serious neurological condition characterised by the sequestration of infected red blood cells (iRBC) in cerebral blood vessels. This event is thought to initiate a cascade of inflammatory reactions that ultimately lead to cerebral damage and often deat ....Malaria kills millions of children every year. A major cause of death is cerebral malaria (CM) resulting from Plasmodium falciparum infection. At present, there is no effective vaccine available and drug-resistant parasites are widespread. CM is a serious neurological condition characterised by the sequestration of infected red blood cells (iRBC) in cerebral blood vessels. This event is thought to initiate a cascade of inflammatory reactions that ultimately lead to cerebral damage and often death. The factors that cause the sequestration of iRBC in the brain are poorly understood. In this project, we will use an experimental model to define the changes that occur in the cerebral vessels during malaria. The identity of the cells and molecules that mediate the binding of iRBC to the blood vessels of the brain will be identified. It is anticipated that results from this work will increase our understanding of the development of pathology in the brain, as well as identify potential targets for modulation to prevent disease.Read moreRead less
Modulation Of HIV-1 Specific T Cell Function By Toll-like Receptor Ligands
Funder
National Health and Medical Research Council
Funding Amount
$214,584.00
Summary
Toll-like receptors (TLR) are highly conserved molecules which allow cells to recognize foreign materials. Factors that bind to these TLRs are called ligands. Ligands that activate or suppress TLR may play a crucial role in influencing how the immune system recognizes and controls HIV. A better understanding of the mechanisms by which TLR ligands, including components of HIV-1, modulate T cell function will open up new avenues for the design of immunotherapeutic interventions and vaccines.
Investigations Into The Architectural And Biophysical Features Of Optimal T Cell Receptor Design
Funder
National Health and Medical Research Council
Funding Amount
$251,877.00
Summary
Humans evolve slowly, pathogens and cancer evolve quickly. Unsurprisingly, our immune systems often lose this arms race and we irreversibly succumb to disease. Catastrophically, >26 million people are lost every year to the these causes. This project will use a new technology to rapidly advance the evolution of human immune receptors to construct a class of super-receptor. These super-receptors may prove decisive weapons in the fight against cancer and infectious disease.
Interplay Of Innate And Adaptive Immunity To Influenza A Virus
Funder
National Health and Medical Research Council
Funding Amount
$555,693.00
Summary
Influenza is an acute febrile respiratory illness caused by influenza virus infection, and may trigger potentially life-threatening complications especially in the young and elderly. Immunity against influenza virus involves integration of the innate and adaptive immune system. We will use cutting-edge 2-photon microscopy to determine the orchestration of innate and adaptive immune cell interactions during viral infection. Results may provide for enhanced therapeutic or protective measures.
Discovery Of Long CD8+ T Cell Epitopes Uncovers A Hidden Reservoir Of Immunodominant, Anti-tumour Responses
Funder
National Health and Medical Research Council
Funding Amount
$480,127.00
Summary
Stimulating killer T cells to eliminate tumours has been one of the ultimate yet elusive goals of cancer vaccine development. Vaccines aimed at stimulating killer T cells are similar to those generated under natural conditions. However, special strategies are needed to vaccinate beneficial killer T cells that are not normally part of the natural immunity. In this project, we will explore such a scenario and dissect the related mechanisms contributing to such differential immune outcomes.