Mechanisms For The Development Of Leukaemia Via Antibody Hypermutation
Funder
National Health and Medical Research Council
Funding Amount
$82,421.00
Summary
During responses to infection, the antibody genes in responding B cells mutate at a high rate, resulting in B cells producing better antibodies. Although essential for long-lived immunity, antibody mutation involves the introduction of DNA breaks which can occasionally cause leukemia or lymphoma. We understand only poorly how DNA repair systems normally make sure that antibody mutation is benign and does not cause cancer.
Physiologic And Aberrant DNA Recombination In B Lymphocytes
Funder
National Health and Medical Research Council
Funding Amount
$408,768.00
Summary
B cells produce antibody which is critical to fight infection. In order to perform this function, antibody genes must first be modified by immune enzymes. However, abnormal DNA attack by these enzymes outside of antibody genes can result in B cell cancer. How the immune system detects and destroys cancerous B cells is poorly understood. This research will provide insight into these processes, and in doing so will further our understanding of how B cell cancers develop and how they are destroyed.
The Regulation And Differentiation Potential Of Human Memory B Lymphocytes
Funder
National Health and Medical Research Council
Funding Amount
$227,036.00
Summary
Antibody produced by our immune system plays a critical role in protecting us from infectious disease. Remarkably our ability to make antibodies is much faster the second time we see the infection. This memory of the previous attack occurs due to the formation of memory B cells that circulate in the blood, sometimes for years, looking for the same intruders. If they detect the infection they rapidly become activated and remake the antibody. These memory cells are very important for our protectio ....Antibody produced by our immune system plays a critical role in protecting us from infectious disease. Remarkably our ability to make antibodies is much faster the second time we see the infection. This memory of the previous attack occurs due to the formation of memory B cells that circulate in the blood, sometimes for years, looking for the same intruders. If they detect the infection they rapidly become activated and remake the antibody. These memory cells are very important for our protection. Vaccines operate by tricking the immune system into making these memory cells, even though the body hasn't seen the actual disease. Although clearly vital for our health little is known about the activation and antibody production by human B memory cells. This project will redress our lack of knowledge by performing a comprehensive evaluation of the properties of this important cell type.Read moreRead less
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.
I am an Immunologist interested in the role of B-lymphocytes, their survival and expression of a novel chemoreceptor in Autoimmunity. I also study the important role of Neuropeptide Y in modulating key immune functions.
Defining The Cellular Interactions For Initiation And Maintenance Of Immunity To Intracellular Pathogens
Funder
National Health and Medical Research Council
Funding Amount
$863,413.00
Summary
This immune system provides our body’s defense against invading organisms like viruses, preventing disease and maintaining health. Immunity involves the interaction of several different cell types that together form arsenals tailored to combat each different infection. Professor Heath will investigate how cells of the immune system orchestrate effective immune responses to viral infections and malaria. He will use this understanding to design novel approaches to vaccination.
Identifying The Underlying Mechanisms Responsible For The Generation Of Pathogenic B Cells In Type 1 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$163,755.00
Summary
Type 1 diabetes (T1D) occurs when the body's own immune system mistakenly attacks and destroys all the beta cells of the pancreas which produce insulin, a hormone essential for regulating sugar levels in the blood. The non-obese diabetic (NOD) mouse develops a form of T1D closely resembling the human disease, and as a model, has led to numerous important insights into its cause. Based on studies in NOD mice, it is now well accepted that a class of cell in the immune system, termed T cells, are r ....Type 1 diabetes (T1D) occurs when the body's own immune system mistakenly attacks and destroys all the beta cells of the pancreas which produce insulin, a hormone essential for regulating sugar levels in the blood. The non-obese diabetic (NOD) mouse develops a form of T1D closely resembling the human disease, and as a model, has led to numerous important insights into its cause. Based on studies in NOD mice, it is now well accepted that a class of cell in the immune system, termed T cells, are responsible for most of the damage to the beta cells in T1D. Recent work in this model, however, has demonstrated that another class of immune cell, termed B cells, also play an important role in T1D as NOD mice made deficient in these cells no longer develop disease. In addition to producing antibodies, B cells are one of the few cell types which are able to take up and present protein fragments in a form recognizable to T cells. Normally, this only leads to the activation of T cells recognising foreign insults, like viruses or bacteria, resulting in their destruction. We have shown that a dangerous population of B cells can arise in NOD mice that can specifically take up beta cell proteins and present them to the T cells, which subsequently become armed to recognise and destroy the beta cells. Just like T cells, B cells that recognize the body's own proteins are normally eliminated in healthy mice and human individuals. This research proposal aims to determine the faulty immune mechanisms that give rise to the beta cell specific B cells in NOD mice. We have also set out to identify the diabetes susceptibility genes which control the generation of this dangerous population of B cells in this model. By understanding how these dangerous B cells are generated in NOD mice, we hope to form the basis for new therapies aimed at inhibiting these cells from forming in T1D susceptible humans, thus preventing the disease at an early stage.Read moreRead less