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.
Phagocytic Clearance And Immune Activation In Malaria
Funder
National Health and Medical Research Council
Funding Amount
$564,644.00
Summary
Macrophage white blood cells clear malaria infected cells by eating them, by three routes- by recognising ANTIBODIES or COMPLEMENT on the cell surface, or by the cell BINDING directly to the macrophage. Each has different results, such as amounts of cytokines produced. Cytokines clear malaria; in excess they can cause fatal immune pathology. We will investigate how variations in amount of antibody and complement and route of uptake of malaria infected cells might determine malaria outcome.
Processes Underlying Establishment And Maintenance Of The Latent HIV Resevoir And Potential Impact Of Integrase Inhibitors
Funder
National Health and Medical Research Council
Funding Amount
$318,044.00
Summary
Therapy for HIV-infected individuals is currently able to control the growth of the virus, but cannot eradicate the viral infection. This is due to a pool of CD4+ T lymphocytes which contain HIV DNA in a latent state, ready to reactivate as soon as therapy is interrupted. This project aims to better understand how this pool of latently infected CD4+ T lymphocytes is established and maintained, particularly how it is linked to the essential T cell survival signal from interleukin 7.
A Functional Autoantibody In Human Narcolepsy: Direct Evidence For The Autoimmune Hypothesis
Funder
National Health and Medical Research Council
Funding Amount
$444,928.00
Summary
Narcolepsy is a chronic disabling sleep disorder causing irresistible sleepiness and, in most cases, brief attacks of weakness on emotional arousal (cataplexy). Other symptoms include a transient paralysis at the beginning or end of sleep and vivid hallucinations at the start of sleep. Symptoms usually appear during adolescence or early adulthood. It affects between one in 1,000 and one in 2,000 people, yet the diagnosis is often delayed for several years because of the lack of a simple diagnost ....Narcolepsy is a chronic disabling sleep disorder causing irresistible sleepiness and, in most cases, brief attacks of weakness on emotional arousal (cataplexy). Other symptoms include a transient paralysis at the beginning or end of sleep and vivid hallucinations at the start of sleep. Symptoms usually appear during adolescence or early adulthood. It affects between one in 1,000 and one in 2,000 people, yet the diagnosis is often delayed for several years because of the lack of a simple diagnostic marker. It has been suspected for some time that narcolepsy is caused by a malfunctioning immune system, but direct evidence for the so-called autoimmune hypothesis has been lacking. We have recently discovered the smoking gun in the form of an autoantibody that circulates in the bloodstream and produces some of the features of narcolepsy on transfer to experimental animals. The identification of the autoantibody, which we term a functional autoantibody because it directly alters the function of nerves thought to be involved in narcolepsy and cataplexy, opens a new chapter in narcolepsy research that has important diagnostic and therapeutic implications. Testing for the autoantibody in subjects recruited from national and international centres for sleep research will determine its value in the diagnosis of narcolepsy and may help distinguish narcolepsy from other sleep disorders. Preliminary findings are encouraging and suggest that the autoantibody is a sensitive and specific marker for human narcolepsy and might lead to a clinically useful diagnostic test. In another part of the project, experimental approaches willl be used to identify an antibody called an antiidiotype that can neutralise the narcolepsy autoantibody and therefore be developed as a therapeutic agent. Finally, experiments have been designed to examine the effect of the autoantibody on neurotransmitters in the brain that are believed to result in cataplexy.Read moreRead less