Regulation Of T Follicular Helper Cell Development And Effector Function In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$419,197.00
Summary
Immune cells mature into distinct populations with specialized functions. One subsets are T follicular helper (TFH) cells which are important for instructing B cells to produce antibodies following infection or vaccination. The means by which TFH cells are generated are unknown. We will determine mechanisms whereby TFH cells are produced and how they function. We hope to design approaches that will modulate the function of TFH cells in cases of immunodeficiencies, autoimmunity or vaccination.
Follicular T Helper Cells: Critical Regulators Of Humoral Immune Responses
Funder
National Health and Medical Research Council
Funding Amount
$272,591.00
Summary
B cells are important cells of the immune system that are responsible for producing antibodies in response to infection with pathogens, such as bacteria or viruses, or following vaccinations. In order for B cells to accomplish this task, they require help from a specialised popualtion of T cells, which are another type of immune cell - these are known as follicular T helper (TFH) cells. Under normal circumstances, T cells and B cells specifically interact with one another within lymphoid tissues ....B cells are important cells of the immune system that are responsible for producing antibodies in response to infection with pathogens, such as bacteria or viruses, or following vaccinations. In order for B cells to accomplish this task, they require help from a specialised popualtion of T cells, which are another type of immune cell - these are known as follicular T helper (TFH) cells. Under normal circumstances, T cells and B cells specifically interact with one another within lymphoid tissues such as tonsils, spleens and lymph nodes - here, they engage in a dialogue, the end result of which is the B cells being instructed to produce the appropriate type of antibodies by T cells. However, if tis process is not regulated, the T cells can deliver too little of too much help - this can result in several different types of diseases of the immune system, such as immunodeficiencies (ie insufficient production of antibodies, resulting in individuals becoming susceptible to infections) or autoimmunity (ie production of inappropriate types of antibodies that can recognise cells of the host, resulting in tissue damage and organ failure). The means by which TFH cells instruct B cells to produce antibodies is not completely understood. This project will seek to determine the mechanism whereby TFH cells carry out this important function by performing detailed examination of them follwoing their removal from tissues such as human tonsils and spleens. In doing so, we hope to design approaches that will allow the function of TFH cells to be improved in cases of immunodeficiencies, or suppressed in situations of autoimmune diseases.Read moreRead less
This application proposes to study in detail the main target cell for HIV infection, namely CCR5+ CD4 T lymphocytes. After 30 years of the pandemic, fundamental knowledge of these cells, such as locations in the body, differentiation from other lymphocytes, and survival, is still lacking. These attributes determine whether or not they will be infected by HIV, whether this can be prevented by vaccines or CCR5 blocking drugs, and whether their long-term survival results in an inability to eradicat ....This application proposes to study in detail the main target cell for HIV infection, namely CCR5+ CD4 T lymphocytes. After 30 years of the pandemic, fundamental knowledge of these cells, such as locations in the body, differentiation from other lymphocytes, and survival, is still lacking. These attributes determine whether or not they will be infected by HIV, whether this can be prevented by vaccines or CCR5 blocking drugs, and whether their long-term survival results in an inability to eradicate HIV.Read moreRead less
Inhibition Of Alloreactivity By Modulation Of Antigen Presenting Cells
Funder
National Health and Medical Research Council
Funding Amount
$504,097.00
Summary
Bone marrow transplantation (BMT) is the most effect treatment for a number of conditions, especially leukemia. Graft versus host disease (GVHD) is a complication of BMT and results in the death of up to 50% of transplant recipients. GVHD occurs when the newly transplanted immune system recognizes the recipient as foreign and mounts and immune reponse against the patients tissues. These studies will focus on identifying and understanding the function of the immune cells which drive GVHD.
Using Single-cell Genomics To Resolve Functional Diversification By CD4+ T Cells In Vivo
Funder
National Health and Medical Research Council
Funding Amount
$1,048,096.00
Summary
During immune responses, individual CD4+ T cells multiply and produce hundreds of descendants, with close relatives within a family often developing very different skills. How such differences emerge from one ancestor remains unclear. We use new methods to look at individual CD4+ T cells in unprecedented detail, allowing us to see how close relatives begin to grow apart. Using this, we hope to find novel ways of educating CD4+ T cells to prevent infectious and immune-mediated diseases.
CD4+ T Cell-independent Immunity Against Salmonellae
Funder
National Health and Medical Research Council
Funding Amount
$550,226.00
Summary
Salmonella typhimurium is an important pathogen in both developed and developing countries where it causes significant HIV-linked morbidity. There is a pressing need to understand how immunity might be established against this organism that will function when the patient is immunocompromised either through age or through a comorbidity like HIV.
Understanding The Role Of CD4 T Cells In Viral Infection: A Means Of Improving Anti-viral Immunotherapy.
Funder
National Health and Medical Research Council
Funding Amount
$672,009.00
Summary
Development of therapies to prevent and treat chronic infections is of the highest priority as they cause considerable clinical challenges and on-going health care costs. Efforts to improve treatment of chronic viral infections, such as those caused by HIV, hepatitis C virus and human cytomegalovirus, require a better understanding of the immune responses needed to control these viruses long-term. This proposal will investigate the role of CD4+ T cells in controlling chronic viral infection.
Role Of Dendritic Cell Subsets In The Generation Of CD4 T Cell Memory
Funder
National Health and Medical Research Council
Funding Amount
$563,554.00
Summary
This project studies the mechanisms responsible for establishing immunologic memory that is generated by vaccination and determines its efficacy. We aim to identify and study previously unacknowledged factors that critically affect the efficacy of vaccination. The results will be significant for both preventative and therapeutic vaccination (cancer, autoimmunity) and will help us to design new vaccines to improve immune function in infection, autoimmunity and cancer.