To Describe The Regional Differences In The Innate Immune System Of The Skin Using Intra-vital Multiphoton Microscopy And Understand Its Functional Consequences In A Cutaneous Parasite Infection Model.
Funder
National Health and Medical Research Council
Funding Amount
$97,182.00
Summary
This study is the first of its kind to map the innate immune system, the body's first line of defence, in the skin - coined the "immune atlas". Researchers have shown regional differences in innate immune cells which could explain how infections develop at different sites of the body. Although they have shown this in a cutaneous leishmaniasis model, a parasite endemic in most parts of the world, it may have implications also for inflammatory skin conditions such as eczema or psoriasis.
Mammals have evolved an array of mechanisms to sense microbes. These immune sentinels must distinguish self from non-self to activate an immune response. The initiation, amplification and quenching of an immune response is carefully orchestrated to eliminate invading pathogens while minimising collateral damage to host tissues. This research focuses on proteins that prevent inflammatory diseases such as cardiovascular disease, hepatitis, inflammatory bowel disease and skin diseases.
We have identified a population of immune cells called ‘resident memory T cells’ that reside in tissues of the body. These resident memory T cells play an important role in controlling infections, but it is also apparent that they can lead to aberrant immune reactions, causing autoimmune diseases. This project aims to further our understanding of these immune cells, including how they can be identified and generated, and how they can be controlled to prevent disease.
Cellular And Molecular Mechanisms Of Transcutaneous Immunisation
Funder
National Health and Medical Research Council
Funding Amount
$190,490.00
Summary
Vaccines are among the most effective medical interventions. The recent discovery that cholera toxin, when applied to the normal skin of humans and laboratory animals, stimulates powerful and protective immune responses to itself, and to other proteins has opened up the possibility of needle-free vaccines in the form of skin patches. How CT brings about this effect is currently unknown. We have discovered that the immune stimulating effect of CT depends upon the production of an immune protein ( ....Vaccines are among the most effective medical interventions. The recent discovery that cholera toxin, when applied to the normal skin of humans and laboratory animals, stimulates powerful and protective immune responses to itself, and to other proteins has opened up the possibility of needle-free vaccines in the form of skin patches. How CT brings about this effect is currently unknown. We have discovered that the immune stimulating effect of CT depends upon the production of an immune protein (cytokine) called tumour necrosis factor (TNF). TNF is known to activate specialised immune cells within the skin (Langerhan's Cells ) and we hypothesise that the interaction beween CT and LC via TNF is the pathway to the potent immune response. In this project we propose to investigate the cells and molecules involved in the immune effects of CT in the skin with a view to the development of new skin based vaccine strategies.Read moreRead less
Antigen Recognition By CD1a-restricted T Cells In The Human Immune System
Funder
National Health and Medical Research Council
Funding Amount
$615,520.00
Summary
Human immunity requires protective T cells that target foreign molecules for removal. Even though substantial populations of T cells exist that recognise lipid molecules, little is known about their basic biology. We will identify and characterise lipid reactive human T cells and examine their response to foreign or self-lipids expressed by infectious organisms and host cells. This work will have important implications in understanding lipid reactive T cells in health and disease.
Some infections can start inflammation that, while controlling the infection, can also attack the body tissues of genetically susceptible people. This inflammation can initiate long term problems including arthritis, diabetes and cancer. Our research program seeks to understand who is genetically at risk of this sort of problem and why, and thus to develop new means to prevent and treat the chronic diseases that are initiated in this way.
Subset Determination Of Tissue-Resident T Cell Memory
Funder
National Health and Medical Research Council
Funding Amount
$473,394.00
Summary
Immunity relies on white blood cells called T cells that circulate around the body and which are also found permanently lodged at body surfaces. It is non-circulating T cells that are the most important in protecting against infection. In this application we propose to show that only a subset of T cells can form the resident population and to identify the molecules that determine T cell residency. This information can then be used for the efficient construction of disease preventing vaccines.
The body’s surfaces are continually under threat from microbes that may cause debilitating disease. Our ability to control such infections relies on our immune system, consisting of different cell types with specialised functions. We will study frontline immune cells that populate barrier tissues such as skin and mucosa where they provide enhanced local protection by responding vigorously on infection. Our studies will guide the development of future therapies harnessing our immune system.