NK Cell Subsets And Their Role In Immune Responses
Funder
National Health and Medical Research Council
Funding Amount
$173,522.00
Summary
Natural killer (NK) cells are 5-10% of white blood cells of the immune system that represent one of our first lines of defense against microbes and cancer development. Recent evidence strongly suggests that NK cells are major cells of importance in the immune system, not only in acting as killers of cancer cells or virus-infected cells, but also in regulating the adaptive memory components of the immune response. Despite our greater knowledge of NK cell biology, we still know very little about t ....Natural killer (NK) cells are 5-10% of white blood cells of the immune system that represent one of our first lines of defense against microbes and cancer development. Recent evidence strongly suggests that NK cells are major cells of importance in the immune system, not only in acting as killers of cancer cells or virus-infected cells, but also in regulating the adaptive memory components of the immune response. Despite our greater knowledge of NK cell biology, we still know very little about the diversity that exists within the NK cell population. The development and maturation of NK cells requires far greater study and this proposal aims to examine this question in the best experimental model, the mouse. We have recently made an important breakthrough concerning the distinct functional behavior of newly discovered NK cell subsets. We now aim to develop a more integrated model of NK cell development, such that vaccines and adjuvants designed to prevent and ameliorate lethal and chronic infectious diseases and cancer can be more rationally designed.Read moreRead less
VITAL: Vaccine Immunomodulation Throughout The Aging Lifespan
Funder
National Health and Medical Research Council
Funding Amount
$795,117.00
Summary
The elderly respond less well to vaccines than their younger counterparts. Flu is particularly dangerous to the elderly. In this proposal we will determine the likely immune mechanism undelying this difference, as well as specifically address the urgent issue of whether prior injection with a whooping cough vaccine makes Flu vaccines less likely to be effective.
Novel Posttranscriptional Pathways The Control Tfh Cell Numbers
Funder
National Health and Medical Research Council
Funding Amount
$647,539.00
Summary
T follicular helper (Tfh) cells are essential for effective antibody responses against infection. Limiting Tfh cells is crucial for selecting the "fittest" B cells and the success of vaccines. Tfh cell accumulation causes autoimmuity and is associated with inadequate B cell responses in HIV infection. We have recently discovered two novel pathways that control Tfh cells. We speculate they regulate different RNAs that influence Tfh homeostasis and aim to elucidate their mechanism of action.
This application seeks information on the factors controlling T cell survival, tolerance and responsiveness to foreign antigens and tumour antigens. Particular attention will be directed to determining how T cells are kept alive through contact with self ligands and cytokines while preserving self tolerance and how anti-tumour responses can improved without augmenting the function of T regulatory cells.
Identifying T Cell Correlates Of Protective Immunity To Malaria In Childhood
Funder
National Health and Medical Research Council
Funding Amount
$396,026.00
Summary
Malaria claims nearly one million lives each year, mostly children. Although those living in endemic regions can acquire natural immunity, it develops slowly and isn`t completely protective. This project studies the impact of different levels of malaria exposure and age on the development of a protective immune response in children. By understanding the effect of high malaria exposure in the development of immunity it is hoped that new avenues for drug development may be identified.
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
Cancer immunotherapy by “checkpoint blockade” boosts the immune response and leads to tumour rejection in some patients. To improve immunotherapy, information will be sought on the capacity of membrane vesicles prepared from dendritic cells (DC) to stimulate immune cells (T cells) in mice and elicit tumour rejection. Experiments are proposed to trace the fate of the vesicles after injection and improve tumour rejection by combination with checkpoint blockade and addition of cytokines.