Immune Dysregulation In HIV Patients With Immune Reconstitution After Highly Active Anti-retroviral Therapy
Funder
National Health and Medical Research Council
Funding Amount
$411,000.00
Summary
As HIV infection progresses to AIDS, there is a depletion of CD4 T-cells from the patient's blood and inhibition of the function of the remaining cells. Some immune defects resolve if the patient is given treatment with highly active anti-retroviral therapy (HAART), but it remains to be determined if the function of the imune system returns fully to normal. We have shown that problems with the regulation of the restored immune system in the first 6 months of treatment can lead to diseases associ ....As HIV infection progresses to AIDS, there is a depletion of CD4 T-cells from the patient's blood and inhibition of the function of the remaining cells. Some immune defects resolve if the patient is given treatment with highly active anti-retroviral therapy (HAART), but it remains to be determined if the function of the imune system returns fully to normal. We have shown that problems with the regulation of the restored immune system in the first 6 months of treatment can lead to diseases associated with Mycobacterial infections (eg: tuberculosis), CMV retinitis, hepatitis B virus or hepatitis C virus. We have defined these conditions as Immune Restoration diseases (IRD) and shown that they occur in one in four individuals who begin HAART from low baseline CD4 T-cell counts. IRD are likely to become common as therapy becomes available in Africa and Asia as patients begin treatment from low CD4 T-cell counts. There is also emerging evidence that dysregulated T-cell responses may cause disease later in the course of immune reconstitution. For example, some patients with undetectable HIV experience opportunistic infections or autoimmune disease after many months of HAART. This project will use West Australian patients receiving optimal therapy for their HIV infection. We will analyse immune activation and T-cell function in patients beginning HAART with low CD4 T-cell counts and patients who have had well-controlled HIV infection for at least 6 months. Blood samples will be collected for the measurement of immunological messengers (cytokines) known to be involved in different types of immune responses. The results will be correlated with the clinical outcome.Read moreRead less
HIV-1 infection is characterised by high levels of virus replication and a progressive loss of immune cells, particularly CD4+ T lymphocytes. Highly active antiretrovial therapy (HAART) for HIV-1 infection results in profound suppression of viral replication, a substantial increase in CD4+ T lymphocytes and a decrease in morbidity and mortality. The primary source of T lymphocytes in early human development is the thymus. Recently, it has been demonstrated that the thymus remains functional thro ....HIV-1 infection is characterised by high levels of virus replication and a progressive loss of immune cells, particularly CD4+ T lymphocytes. Highly active antiretrovial therapy (HAART) for HIV-1 infection results in profound suppression of viral replication, a substantial increase in CD4+ T lymphocytes and a decrease in morbidity and mortality. The primary source of T lymphocytes in early human development is the thymus. Recently, it has been demonstrated that the thymus remains functional throughout adult life. The role of the thymus in HIV-1 infection remains controversial. Studies of the role of the thymus in HIV-1-infected individuals has been limited by the lack of a marker of thymic function in vivo. We have recently developed a novel assay to quantify cells of recent thymic origin by taking advantage of certain molecular events that occur in the thymus during the production of new T lymphocytes. This molecular event creates a circular piece of DNA, called a T-cell receptor excision circles (TREC). TREC concentration in the periphery will increase with an increase in thymic output but will reduce in the presence of T cell proliferation or cell death. In order to determine the contribution of the thymus to immune reconstitution following HAART, we plan to study the dynamics of thymus function in HIV-1 infection by measuring TREC and T cell turnover in HIV-1 infection prior to and following HAART. In a subgroup of individuals, more commonly seen following treatment of HIV-1 infection in children, there is an increase in CD4+ T lymphocytes in the absence of a significant reduction in viral suppression. The role of the thymus in this unique subset of individuals will be studied.Read moreRead less
Immunomodulatory Molecules Of Parasitic Helminths As Novel Therapeutics For Allergic Disorders.
Funder
National Health and Medical Research Council
Funding Amount
$321,532.00
Summary
Australia has one of the highest rates of asthma in the world with almost 3 million Australians are affected by this disease. Previous research has shown that infection with various types of parasitic worms lessens the severity of asthma. The aim of this research is to find out why this happens and to isolate the ingredients from the parasite that suppress asthma. Once found, these molecules can be used to create new drugs for the prevention of asthma and allergies in children and adults.
Targeting The Human Immune Response To Bacterial Superantigens.
Funder
National Health and Medical Research Council
Funding Amount
$165,424.00
Summary
This research investigates the human immune response to infection with toxin producing bacteria. Toxins activate the human immune system which can lead to serious illness or the development of disease that can progress rapidly and be associated with high rates of morbidity and mortality. Investigating the harmful effects of infection with toxin producing bacteria in humans and the damage caused by their toxins is essential for the development of effective therapeutic strategies.
Differences In Neonatal Immune Regulation In The Developing And Developed World: Implications For Neonatal Vaccinations?
Funder
National Health and Medical Research Council
Funding Amount
$332,083.00
Summary
This project will study the effect of adverse living conditions such as high microbial exposure, malnutrition, environmental tobacco smoke and malaria infection on the development of a newborn's immune system,by comparing immune response between newborns in Papua New Guinea and in Western Australia. This study will help us to understand the high susceptibility of children in the developing world for infectious diseases and to develop better prevention strategies.
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.
This project will determine how viruses prevent transmission of messages within cells which orchestrate responses of our immune system to infection and whether our current therapies improve this defect. This knowledge will help us to better understand why our immune system is not able to control chronic virus infection and improve therapies for these diseases.
Improving Protection Against Childhood Tuberculosis: The Influence Of BCG Vaccine Strain And Age On Protective Immunity
Funder
National Health and Medical Research Council
Funding Amount
$473,739.00
Summary
BCG vaccine is of vital importance in the fight against the increasing problem of TB worldwide, particularly in children. This project will compare the 3 most commonly used different strains of BCG vaccine to determine which produces the best protective immunity in newborns. It will also determine whether BCG at birth or at 2 months of age provides better protection. Optimising the timing and strain used for BCG immunisation would prevent large numbers of cases and deaths from TB at low cost.