Our immune system protects us from all kinds of infections, from fungal infections to bacterial and viral attack. Understanding how it does this – and what goes wrong when disease occurs – is a key goal for researchers in the Immunology Division of the Garvan Institute of Medical Research.
In recently published studies, researchers Professor Stuart Tangye, Dr Elissa Deenick and Dr Cindy Ma and their teams have uncovered new insights into the underlying biology of the immune system in humans – from the diverse roles of different classes of immune cells to how the immune system reacts to viral infections or to food substances that cause allergies. Their work has yielded a number of promising clinical targets for further investigation.
Immunodeficiencies hold the key to normal immune function
To understand the molecules and cells that make up the human immune system, the researchers look to individuals with primary immunodeficiencies – chronic genetic disorders in which small parts of the immune system are unable to do their job.
Prof Tangye describes their work: “There are a great many different primary immunodeficiencies, each with different characteristics. In some, for example, the individuals affected may be particularly susceptible to fungal infections that cause thrush, while in others the individuals may be more prone to recurrent respiratory viral infections.
“From a research perspective, this is invaluable because we can look in molecular detail at what has gone wrong in that individual’s immune system – and link it to the underlying genetic mutation that has caused the immunodeficiency.”
A multitude of T cells – and a multitude of roles
In one study, published last month in The Journal of Experimental Medicine, the researchers investigated 88 patients with distinct genetic mutations that affect their immune system, predisposing them to different conditions – for example, infections with viruses, bacteria or fungi, or allergic reactions to substances in food. They looked at the role of T cells, vital immune cells that secrete chemical messages to orchestrate the immune response, in these conditions. Different types of T cells provide immunity against specific infectious pathogens.
“By looking at a number of patients with a range of clinical conditions and different genetic mutations, we were able to identify the specific genes responsible for the functioning of specific types of T cells, providing new links in the biological pathways underlying these diseases,” explains Dr Ma.
“The findings help us understand how different types of T cells work, but they also provide potential clinical targets to help fight immunodeficiency and autoimmunity, and also possibly to improve the immune response to vaccination.”
Prof Tangye was invited to present these findings at ICI2016, the International Congress of Immunology 2016, which is being held in Melbourne this week.
Extreme immunodeficiency yields insights into common infections
The immunologists have also been studying a primary immunodeficiency disorder called Hyper IgE syndrome. This disorder is rare, but patients suffer devastating immune abnormalities that leave them open to severe and recurrent viral and fungal infections and to other conditions such as allergies and eczema.
“We research patients with extreme disease in order to study common infections to which we may all be susceptible,” says Dr Deenick.
“By studying how antibody response or cell communication pathways go awry in the immune cells of such patients, we can determine what parts of the cell are needed for immune response to specific infections, and therefore what parts we can target medically to improve immune response.”
One of the team’s findings provides new insight into the biology behind allergic reactions. They identified distinct differences between the immune response to food allergens and to environmental factors such as house dust mites.
Dr Ma says, “An allergic reaction to food can be mild, such as a minor skin rash, or life-threatening, such as anaphylaxis. Understanding the biology behind these reactions lays the groundwork for developing medical interventions to aid the immune response in such situations.”
Drs Ma and Deenick have also presented this work to the international immunology community at the ICI2016 conference this week.
This work was performed with a number of international collaborators including Professor Jean-Laurent Casanova of The Rockefeller University, New York, with whom Prof Tangye and the team have been working closely on primary immunodeficiency for a number of years.
The immunology team is grateful to the patients and families that participated in these studies, and this research was supported by grants from the National Health and Medical Research Council.