Absence Of CC Chemokine Receptor 6 Dysregulates The Humoral Immune Response.
Funder
National Health and Medical Research Council
Funding Amount
$524,820.00
Summary
The individual steps leading to the activation and differentiation of B cells and the formation of mature functional germinal centres have been investigated in detail and are well understood. In contrast, the underlying molecular signals, which regulate the different events and prevent either autoimmunity or immunodeficiency are still not fully comprehended. This proposal will address these regulatory steps that prevent autoimmunity.
Antigen Receptor Sharing By Lymphocytes During An Immune Response
Funder
National Health and Medical Research Council
Funding Amount
$286,328.00
Summary
A successful immune response relies on the ability of immune cells to quickly mount a specific offensive against invading foreign pathogens like bacteria or viruses. The specificity of this offensive is governed by receptors that can recognise pathogens. To survive an infection the immune system must rapidly expand the number of immune cells that have receptors that recognise, and can therefore specifically combat, the infection. The underlying theory of immunology, the clonal selection theory, ....A successful immune response relies on the ability of immune cells to quickly mount a specific offensive against invading foreign pathogens like bacteria or viruses. The specificity of this offensive is governed by receptors that can recognise pathogens. To survive an infection the immune system must rapidly expand the number of immune cells that have receptors that recognise, and can therefore specifically combat, the infection. The underlying theory of immunology, the clonal selection theory, states that this expansion is mediated by the proliferation of immune cells selected on the basis of expressing a pathogen specific receptor. We hypothesise that in addition to this proliferation the immune system may also expand the number of immune cells expressing pathogen-specific receptors by transferring these receptors between cells by a means of cell-membrane sharing. Indeed, we have evidence that this does occur both in the test tube and in animals and can function to amplify the number of immune cells that can specifically recognise a pathogen and thereby help with immune response development. This grant aims to further advance our understanding of this novel phenomenon.Read moreRead less
In this project, we will determine how a protein called ACKR4 suppresses antibody production and determine whether inhibiting its function will enhance the effectiveness of vaccination.
Tumour B-cells From Lymphomas Are Resistant To ATP-mediated Apoptosis Due To Non-functional P2X7 Receptors
Funder
National Health and Medical Research Council
Funding Amount
$226,320.00
Summary
Adenosine triphosphate (ATP) is an important constituent normally present inside cells. When added to normal lymphocytes (or released by cells lining the vessel wall or in lymph nodes), ATP acts from outside these cells to open a pore as well as activate an enzyme which digests the lipid envelope of the cell. This loss of lipid covering of the cell produces a leakiness to various constituents of the cell which gradually leads to death of normal lymphocytes. However in the malignant lymphocytes o ....Adenosine triphosphate (ATP) is an important constituent normally present inside cells. When added to normal lymphocytes (or released by cells lining the vessel wall or in lymph nodes), ATP acts from outside these cells to open a pore as well as activate an enzyme which digests the lipid envelope of the cell. This loss of lipid covering of the cell produces a leakiness to various constituents of the cell which gradually leads to death of normal lymphocytes. However in the malignant lymphocytes of human lymphomas this mechanism of cell death does not operate. The loss of function of this 'death receptor' explains why in the lymphomas there is a progressive accumulation of malignant lymphocytes which give enlargement of lymph nodes and spleen and leads to death of the patient. Knowledge of the defect in this pathway of cell death will enable new strategies to be introduced to control this malignant disease.Read moreRead less