Day of Immunology
29th April 2020

Day of Immunology 2020: Celebrating the impact of immunology on our lives

The 29th of April marks the day all immunologists celebrate; it is the International Day of Immunology. But we immunologists want to share our love of immunology and our recent research in immunology with the world. To do this, Catriona Nguyen-Robertson, together with members of the editorial team at Immunology & Cell Biology, have selected six recently published studies to showcase for the Day of Immunology 2020. These studies highlight how research in immunology contributes to our everyday health and wellbeing with a particular focus on studies related to vaccine development and efficacy but also including studies that shed light on immune-associated diseases such as graft-versus-host disease and cystic fibrosis.

The scientific writing style requires precision, accuracy, and explicit detail, but this style may make its relevance to everyday life difficult to grasp. Thus, the authors have kindly provided a summary of their research in plain language, and to further celebrate this work, short video bytes have been produced based upon these abstracts. We invite you to enjoy and to share these videos not only on the 29th of April but throughout the year.

Finally, I wish to acknowledge and thank the authors for providing such excellent summaries, Wiley for producing these engaging video bytes, and Catriona and the ICB editorial team for organizing this Day of Immunology initiative.

-Anne La Flamme, Immunology & Cell Biology Editor-in-Chief

Celebrate the International Day of Immunology virtually with the Australian and New Zealand Society for Immunology this May. Enjoy our stimulating public forums and learn about your immune system from the comfort of your home. For the parents who are home schooling, it is a great opportunity for school students to learn about immunology and world class research performed in Australia and New Zealand.

3rd May Viruses, Sun Exposure and the Immune System (click here to book).

7th May 'You Amazing Immune System' in partnership with Science In the Pub Tasmania (click here to book).

15th May 'Gut Immunology - Trouble in the Deep South' (click here to book).

Immunology on the radio

  • 19th April, Prof Colby Zaph (Monash University), Prof Nicola Harris and Dr Lisa Mielke discuss their research on gut immunology on Einstein A Go-Go, 102.7FM 3RRR, (Listen to the recording here).
  • • 26th April at 11AM AEST, A/Prof Menno Van Zelm (Monash University) will discuss Primary Immunodeficiency on Einstein A Go-Go, 102.7FM 3RRR, Melbourne (On digital radio live (Global RRR app))

For more information visit the Day of Immunology website and follow us on twitter, facebook or instagram. #DoImmuno

Towards a universal pneumococcal vaccine

Shannon David, Mohammed Alsharifi, Timothy R Hirst, James Paton

The bacterium Streptococcus pneumoniae is carried in the nose of many healthy people, persisting as an ‘asymptomatic coloniser’, meaning that is causes no symptoms or disease.

Towards a universal pneumococcal vaccine

Shannon David, Mohammed Alsharifi, Timothy R Hirst, James Paton

The bacterium Streptococcus pneumoniae is carried in the nose of many healthy people, persisting as an ‘asymptomatic coloniser’, meaning that is causes no symptoms or disease. However, S. pneumoniae can also invade other parts of the body to cause severe infections, including pneumonia, sepsis, and meningitis. Often, it is a separate infection by respiratory viruses, such as influenza or coronavirus, that leads to life-threatening secondary bacterial infection by S. pneumoniae. S. pneumoniae is the world's most lethal bacterial pathogen causing around 1 million deaths every year, with the majority of these fatalities in young children and the elderly.

Vaccines are available to combat S. pneumoniae, although these protect against less than 25% of all the different S. pneumoniae serotypes (variants) known to be carried by humans. Consequently, serotypes not covered by these vaccines are emerging as major causes of infection and invasive disease. Alarmingly, we have no preventative measures in place to protect the population from these emerging serotypes.

Researchers at the University of Adelaide’s Research Centre for Infectious Diseases, in conjunction with GPN Vaccines Ltd, have developed a universal vaccine: a new class of vaccine to generate immunity against all serotypes of S. pneumoniae. It contains S. pneumoniae cells which have been inactivated by exposure to gamma irradiation, and triggers robust immune responses resulting in broad protection.

To further enhance the safety and efficacy of the vaccine, they modified the pneumococcal vaccine strain to have attenuated growth. By introducing a mutation in the gene, psaA, the vaccine strain was unable to grow unless it was provided with manganese as a nutritional supplement. This mutation boosted activation of first-line immune responses and improved protection against lethal S. pneumoniae infection when tested in animals. This is a very promising vaccine product that the team is progressing into human trials.

Read the full article in Immunology & Cell Biology

Entering the Battle Ground: The signals that call B cells to war

Erica Brodie and Marcus Robinson

Soluble proteins, called antibodies, protect us from infectious disease by binding to and neutralizing invading viruses, bacteria and other infectious organisms (collectively called pathogens)..

Entering the Battle Ground: The signals that call B cells to war

Erica Brodie and Marcus Robinson

Soluble proteins, called antibodies, protect us from infectious disease by binding to and neutralizing invading viruses, bacteria and other infectious organisms (collectively called pathogens). One of the interesting things about antibody responses is that over time, the antibodies produced become better at binding to specific pathogens.

Antibodies become better binders because the cells that are the antibody factories —B cells—compete with each other, and only the best binders hang around to contribute to the immune response. To do this, B cells that recognize the invading pathogen, or molecules from that pathogen, have to enter a special battle ground in lymph nodes, called germinal centres. To get inside the germinal centres, B cells turn on expression of a protein called BCL6. Once inside, B cells are given signals by the generals of the immune system, T cells, that let them know they are the best binders, they should make more copies of themselves, and that they should go on to make antibodies.

Learning how the individual signals given by the T cells work in germinal centres has been difficult because there hasn’t been a good way to make B cells grown in a lab “think” that they are in germinal centres. Monash University researchers recently established a way to achieve this.

Robinson et al. used cells called fibroblasts to mimic the lymph node architecture. The fibroblasts were genetically manipulated to express a molecule that T cells use to activate B cells: CD40 ligand. Together with additional factors, BCF-1 and IL-21, normally released by T cells, they could trick the B cells into thinking they were in germinal centres and express BCL6. The study also confirmed that a B cell activating factor (BAFF), made outside of the germinal centres themselves, helped the B cells survive when they stopped expressing BCL6.

Each of the signals—BCF-1, IL-21 and BAFF—had a unique effect on the B cells and it was only their combined efforts that worked. While there may be other factors also involved, this study provides a good base from which to explore the intricacies of germinal centre B cell biology outside the body.

Read the full article in Immunology & Cell Biology

Graft-versus-host disease: stopping the transplant from attacking the person

Nicholas J Geraghty, Debbie Watson and Ronald Sluyter with Neil Pennock

Blood cancers such as leukaemia, lymphoma and myeloma, are cancers of the immune system and are common in both children and adults.

Graft-versus-host disease: stopping the transplant from attacking the person

Nicholas J Geraghty, Debbie Watson and Ronald Sluyter with Neil Pennock

Blood cancers such as leukaemia, lymphoma and myeloma, are cancers of the immune system and are common in both children and adults. Like most cancers, blood cancers are usually treated using chemotherapy or radiotherapy, but these therapies are not always successful at curing the underlying disease. In such instances, these people may undergo a stem cell transplant using blood stem cells or bone marrow from a matched, healthy donor. This therapy seeks to replace the patient’s diseased bone marrow, the source of the cancer, with healthy cells from a donor to generate new, cancer-free bone marrow and a working immune system.

Unfortunately, in about half of these transplant recipients, immune cells in the donor transplant (“graft”) attack tissues of the person with cancer (“host”), leading to a debilitating and often fatal condition known as graft-versus-host disease (GVHD). As part of this condition, the damaged “host” cells release an immune molecule, called adenosine triphosphate (ATP), which can activate the “graft” immune cells to promote inflammation and damage the recipient’s tissues such as the liver, gut and skin.

In their study published in Immunology & Cell Biology, Geraghty, Watson and Sluyter modelled a stem cell transplant and GVHD by injecting human blood (immune) cells into mice with an impaired immune system. Using a drug that stops immune cell molecules called CD39 and CD73 from degrading the released ATP, they observed worse GVHD in these mice. This study and their previous studies suggest that the released ATP activates a molecule on immune cells called P2X7 to promote GVHD. As such, therapies that block P2X7 may help limit or prevent GVHD in people with blood cancer who have undergone a stem cell transplantation.

Read the full article in Immunology & Cell Biology

When one vaccine helps another: can the MMR vaccine boost the effects of other vaccines?

Catriona Nguyen-Robertson

We are immunised with a range of vaccinations from birth through to adulthood to protect ourselves against many diseases.

When one vaccine helps another: can the MMR vaccine boost the effects of other vaccines?

Catriona Nguyen-Robertson

We are immunised with a range of vaccinations from birth through to adulthood to protect ourselves against many diseases. By providing small doses of a weakened or killed pathogen (viruses and bacteria), vaccines stimulate the immune system to react as if there were a real infection, and generate an army of immune cells and proteins that will remember the pathogen and fight it off if it enters the body later. Part of this immune “memory” are antibodies, proteins that prevent pathogens from infecting cells of the body and mark them for attack by immune cells. Antibodies are shaped to target specific pathogens and hang around long after vaccination.

The goal of vaccines is to generate specific immunity against specific pathogens. However, vaccines that contain weakened forms of pathogens, such as the measles, mumps, and rubella (MMR) vaccine, can have additional “non-specific” effects on the immune system.

Children who are infected with measles have a higher mortality rate than children who are vaccinated against the disease and therefore do not contract it. This can be explained both by the fact that the measles virus commonly infects immune cells, thereby increasing susceptibility to other infections, and also by the vaccine’s beneficial but “non-specific” effects.

Zimmermann and colleagues at the Royal Children’s Hospital examined the cross-protection of the MMR vaccine against other diseases. They immunised 12-month-old babies with vaccines for MMR, and Haemophilius influenza type b and meningitis C (Hib/MenC), both of which cause meningitis. The group then compared the levels of antibodies the babies had for diseases they had been previously immunised against (e.g. pneumococcal disease and tetanus) to babies not yet immunised with MMR and Hib/MenC.

Overall, there were no great differences in amounts of antibodies targeting pathogens that cause other diseases, however there was a slight boosting of antibody numbers against tetanus. This study therefore highlights that the MMR vaccine not only protects against measles, mumps, and rubella, but can also be cross-protective by enhancing the effects of previous vaccinations in ways that we don’t yet fully understand.

Read the full article in Immunology & Cell Biology

Cluing in on Cystic Fibrosis

Emily Mulcahy

Cystic fibrosis (CF) is a genetic condition that affects 1 in every 2500 births in Australia.

Cluing in on Cystic Fibrosis

Emily Mulcahy

Cystic fibrosis (CF) is a genetic condition that affects 1 in every 2500 births in Australia. People born with CF have a build-up of mucous in their lungs that leads to chronic infection, making it progressively harder to breath and reducing their life expectancy to an average age of 38 years.

The mutation that causes CF is found in many cells of the immune system but the effects of this have not been widely researched. If an otherwise healthy person were to get a lung infection, their immune system would act to eliminate this infection appropriately. However, the immune system of those with CF does not manage to do this effectively. In fact, the resulting inappropriate immune responses cause further damage to the lungs. Understanding the differences in the immune cells of people with CF is the first step to understanding how to correct it and hopefully increase quality of life for those with the disease.

Innate immune cells are one of the first lines of defence against pathogens that enter the body. A recent study by Emily Mulcahy and her colleagues investigated the proportions of these cells in the blood of people with CF and compared them to the blood of healthy people. The researchers were able to use a small amount of blood to analyse multiple innate immune cells at once. They found many differences in the numbers of these different cells in people with CF and some of these changes were associated with poorer lung function. This shows that measuring these immune cells can reflect lung health in people with CF and could be used as an indication of prognosis. Correction of these innate immune cell irregularities could also potentially lead to improved lung health in those with CF.

Read the full article in Immunology & Cell Biology

Nature versus nurture: which influences the response to vaccination?

Catriona Nguyen-Robertson

Vaccination is one of the most effective ways to prevent diseases. A vaccine helps the body’s immune system to recognise and fight pathogens (e.g. viruses or bacteria), which then keeps us safe from the diseases they cause.

Nature versus nurture: which influences the response to vaccination?

Catriona Nguyen-Robertson

Vaccination is one of the most effective ways to prevent diseases. A vaccine helps the body’s immune system to recognise and fight pathogens (e.g. viruses or bacteria), which then keeps us safe from the diseases they cause. At the core of this protection is the generation of antibodies, proteins that bind and neutralise invading pathogens, and encourage immune cells to kill infected cells to clear the infection. However, there is a large amount of variation across the population in the way we respond to vaccines – some people fail to produce enough protective antibodies following immunisation.

Poyntz and colleagues investigated why this variation exists. They immunised the same mice species obtained from different vendors to assess their antibody production. Given that all mice were kept under the same conditions but still had differences in their antibody responses, it did not seem to be environmental factors (e.g. gut microbiota) that drove diverse antibody, but rather, the underlying genetic factors.

In looking for genetic influences that contribute to response to immunisation, the researchers found that mice who had low amounts of protective antibodies had a defect in their ability to “class-switch” from forms of antibodies that provide a minimal amount of protection to forms that provide the best protection. They then sequenced the genomes of these mice to identify differences in the genes responsible for regulating this process.

In this case, it was genetic factors that influenced the immune response to vaccinations – nature rather than nurture. Knowing the factors that influence how well individuals respond to vaccines provides insight into how we can implement strategies that boost vaccine efficacy.

Read the full article in Immunology & Cell Biology