Chemokine And Chemokine Receptor Regulation Of T Lymphocyte Traffic To Lymph Nodes
Funder
National Health and Medical Research Council
Funding Amount
$195,691.00
Summary
The movement of white blood cells from the bloodstream into the tissues is a key component of how we defend ourselves against infection and cancer, and also develop unwanted illnesses such as allergy. In particular, the migration of cells into lymph nodes is a critical step in the development of an efficient immune response. Surprisongly little is known about the control of this important cell trafficking process. In this research, the signals that control the movement of white blood cells are b ....The movement of white blood cells from the bloodstream into the tissues is a key component of how we defend ourselves against infection and cancer, and also develop unwanted illnesses such as allergy. In particular, the migration of cells into lymph nodes is a critical step in the development of an efficient immune response. Surprisongly little is known about the control of this important cell trafficking process. In this research, the signals that control the movement of white blood cells are being studied, notably a specialised family of immunological hormones, known as chemokines. Our initial studies suggest that chemokines are indeed the factors which control the traffic of the most important cell type - T cells, into lymph nodes. This research will examine how the activity of specific chemokines controls the influx of particular groups of T cells and subsequently determines the characteristics of the overall immune response taking place in the lymph node.Read moreRead less
Dissecting The Contribution Of CD103+ DC To Priming Of Virus-specific CD8 T Cells
Funder
National Health and Medical Research Council
Funding Amount
$336,767.00
Summary
Dendritic cells are key regulators of T cell responses against pathogens. This project will examine the contribution and individual function of distinct dendritic cell to the initiation of adaptive immune responses against herpes-simplex virus. Unraveling the delicate interplay between different dendritic cells will provide novel insights into host-pathogen interactions and will have important implications for the development of efficient vaccination strategies.
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.
Role Of The Mast Cell Product Histamine In Ultraviolet Radiation Induced Systemic Immunomodulation
Funder
National Health and Medical Research Council
Funding Amount
$393,750.00
Summary
The harmful effects of ultraviolet radiation on skin, as exemplified by sun exposure, are well recognised: sunburn, premature ageing of skin, and induction of skin cancer. Indeed, skin cancers are the most common cancers in Australia. Increasingly recognised now is that UV radiation can alter the immune system. This is of particular relevance to the development of skin cancer: alteration of the immune system is critical to outgrowth of UV-induced cancers. The intact immune system is otherwise ab ....The harmful effects of ultraviolet radiation on skin, as exemplified by sun exposure, are well recognised: sunburn, premature ageing of skin, and induction of skin cancer. Indeed, skin cancers are the most common cancers in Australia. Increasingly recognised now is that UV radiation can alter the immune system. This is of particular relevance to the development of skin cancer: alteration of the immune system is critical to outgrowth of UV-induced cancers. The intact immune system is otherwise able to reject the great majority of UV-induced skin cancers. This effect of UV radiation on the immune system may be relevant to other diseases. It may alter the course of some infections, change the way the body responds to vaccination, and may also have a role in some immune-related diseases such as multiple sclerosis. How it is that these wavelengths just beyond visible light can affect the immune system is the subject of this project. We know that UV radiation can penetrate only a short way into the skin, yet can have widespread effects on the immune system. Our research to now has shown that a particular cell type sitting just below the surface of skin, the dermal mast cell, is essential. We've also demonstrated some of the complexity of the early response to UV exposure - both a chemical (cis-urocanic acid) in the very outermost layer of skin, and nerves in the skin, have roles. Importantly, anti-histamines can inhibit UV effects on immune responses. Additional lines of evidence also point to histamine, a product of mast cells, as playing a pivotal role in the immune alterations following UV exposure. Our research aims to characterise the effects of histamine on cells central to the development of immune responses, known as dendritic cells, and define the mechanisms of the effect in experimental models. In collaboration with researchers in the UK, we will further characterise the role of mast cells in UV alterations to immunity in humans.Read moreRead less
Mechanism Of Breast Cancer Metastasis: Tumour Cell Remodelling Of The Extracellular Matrix
Funder
National Health and Medical Research Council
Funding Amount
$377,331.00
Summary
The main complication in breast cancers leading to death is metastatic relapse. This research aims to understand the role for a protease that promotes spread of breast cancer to the lymph nodes and lungs. The outcomes will identify a novel process that leads to lymph node metastasis and offer a new target for therapies that prevent relapse and tests to identify breast cancer patients at risk of relapse.
Compartmental Analysis Of T-cell Responses In Thoracic Malignancies
Funder
National Health and Medical Research Council
Funding Amount
$851,403.00
Summary
To improve immune therapy for cancer we have to be able to determine how cancer patients ‘see’ mutated cancer proteins. Blood is the easiest & most useful source of immune ‘killer’ cells for that task, but the lymph node that drains the tumour and the fluid that bathes a tumour probably contain a much higher number of these killer cells than blood. If so, studying them would help us better track responses to therapy and enable us to choose the best mutated proteins for a vaccine.
POSNOC (Positive Sentinel Node – A Randomised Trial Of Adjuvant Therapy Alone Versus Adjuvant Therapy Plus Clearance Or Axillary Radiotherapy)
Funder
National Health and Medical Research Council
Funding Amount
$1,223,428.00
Summary
POSNOC (POsitive Sentinel NOde – adjuvant therapy alone versus adjuvant therapy plus Clearance or axillary radiotherapy) will address the key unresolved challenge in breast cancer surgery. A controversial US trial, ACOSOG Z0011, indicates that many breast cancer patients with limited disease in the sentinel node can safely avoid further nodal surgery. This would be a major advance, but there is widespread doubt that the results are broadly applicable. POSNOC will clarify this key issue.