The Appendix In Intestinal Immunity And Inflammatory Bowel Disease
Funder
National Health and Medical Research Council
Funding Amount
$465,210.00
Summary
Inflammatory bowel diseases (IBD) consist of two entities: ulcerative colitis and Crohn's disease. IBD causes relapsing and remitting gut inflammation in relatively young populations of patients. Our understanding of causes of IBD is poor, but the diseases involve an interaction between the intestinal immune system, genetic predisposition and bacteria in the gut. One unexplained observation, made by a number of groups, is that removal of the appendix, especially if performed when young, protects ....Inflammatory bowel diseases (IBD) consist of two entities: ulcerative colitis and Crohn's disease. IBD causes relapsing and remitting gut inflammation in relatively young populations of patients. Our understanding of causes of IBD is poor, but the diseases involve an interaction between the intestinal immune system, genetic predisposition and bacteria in the gut. One unexplained observation, made by a number of groups, is that removal of the appendix, especially if performed when young, protects against the later development of ulcerative colitis and probably Crohn s disease. If IBD does develop following earlier appendicectomy, it tends to be less severe. In this project, we plan to examine the immune features of the appendix, in human and mouse. The appendix is a major source of immune cells in the intestine but the nature of these cells and their functions are poorly understood. The aims of the project will explore the nature of immune cells, known as T lymphocytes, isolated from human and mouse appendices. Changes with age will be examined, to explain the age-related nature of the appendicectomy-IBD link. Anti- and pro-inflammatory characteristics of the cells will be studied, the migration pathways of these cells from appendix to other parts of the intestine will be clarified, and the therapeutic potential of these T cells in a mouse model of IBD will be elucidated. In addition, this will be the first study to develop and analyse a mouse model of appendicitis, which is very poorly understood. These studies will make important observations relevant not only to IBD, but to the immune function of the intestine, with implications for our fundamental understanding of the way we are protected from our hostile environment.Read moreRead less
Development And Function Of NKT Cell Subsets In Humans
Funder
National Health and Medical Research Council
Funding Amount
$533,828.00
Summary
NKT cells are a type of white blood cell that help to control the function of the immune system. Many studies have reported an association between low NKT cell levels and increased rates of cancer and autoimmune diseases such as type 1 diabetes (T1D). Unfortunately, NKT cells are a relatively recent discovery and their function is not well understood, especially in humans. For example, it has only recently been discovered that there are different types of NKT cells with different functions. This ....NKT cells are a type of white blood cell that help to control the function of the immune system. Many studies have reported an association between low NKT cell levels and increased rates of cancer and autoimmune diseases such as type 1 diabetes (T1D). Unfortunately, NKT cells are a relatively recent discovery and their function is not well understood, especially in humans. For example, it has only recently been discovered that there are different types of NKT cells with different functions. This lack of knowledge has prevented us from understanding how NKT cells normally prevent disease, and how we should treat diseases associated with low NKT cell numbers. In this project, we will study human NKT cells to determine how many different subsets exist, how they develop, and what role they play in the immune system. Importantly, we will use our knowledge to compare NKT cells from healthy donors and patient groups with T1D and cancer to determine exactly what is wrong with the NKT cells in these people. While both diseases are already linked to low NKT cell numbers, we do not know how these problems arise, or if some types of NKT cells are more important than others. Our study will determine how different types of NKT cells develop and function in humans and therefore allow a much more detailed understandng of how to diagnose and treat NKT cell deficiencies associated with different diseases.Read moreRead less
T-follicular Helper Cell Subsets That Induce Protective Anti-Plasmodium Falciparum Antibodies
Funder
National Health and Medical Research Council
Funding Amount
$456,262.00
Summary
Malaria claims at least half a million lives each year, the majority of them in children under the age of 5 years. In order to development effective vaccines malaria it is critically important that we increase our understanding of the key mechanisms governing the induction of protective immune responses in naturally exposed populations. This project will examine the role of one important cell subset - T-follicular helper cells - in the development of immunity against malaria.
Molecular Dissection Of Cytokine-mediated Regulation Of Human B-cell Differentiation.
Funder
National Health and Medical Research Council
Funding Amount
$119,314.00
Summary
Interleukin 21 is a molecule which activates B cells. Defects in this pathway cause immunodeficiency where individuals cannot make antibodies, while constant activation has been reported in mouse models of autoimmunity. Examining these pathways will shed light on the causes of human immune disease, and may reveal molecules that could be targeted for the treatment of immunodeficiency and autoimmunity. Amplification of normal immune responses could lead to the development of improved vaccines.