In a breakthrough discovery a research team at The Australian National University has found a critical circuit in the immune system which when faulty causes loss of immunization memory and would explain why some people suffer frequent and repeated infections.

The memory circuit identified by the research team involves a gene and protein called DOCK8, which helps white blood cells to form synapses- tiny points of cell contact- that resemble the synapse connections responsible for laying down memory in the brain.

Whilst the gene circuits that allow our immune system to lay down long-term memory are still largely a mystery to scientists, an increased understanding of these would not only lead to enhanced vaccines but also improve the treatment of cancer, transplant rejection, autoimmunity and allergy.

"Vaccines that provoke long-lasting immunity are among the greatest advances delivered by health research, but the circuits that determine whether they work or not have been among the most difficult to decipher," said Professor Goodnow from The John Curtin School of Medical Research and co-leader of the research team.

"Not only does this discovery reveal a critical step in immunological memory, but it exemplifies the advances made possible by developing the field of phenomics - a result of long-term strategic investment by the ANU, the Commonwealth Government through its NHMRC, ARC and NCRIS programs, and international agencies like The Wellcome Trust."

Lapses of immunological memory also explain the reactivation of infections responsible for cold sores, shingles, yeast infections, and possibly some forms of cancer.

Dr Katrina Randall is a clinical immunologist from the Canberra Hospital and co-lead the ANU research team with Professor Goodnow. "Immunity normally lasts for years after we are immunized or infected because our immune system remembers the shape and "fingerprints" of an infecting microbe and keeps making antibodies against them," she explained.

"When immunological memory wanes we become susceptible to infection again, and need a reminder in the form of a booster immunization. For some vaccines like the tetanus vaccine this occurs after several years, and for many experimental vaccines their memory has so far proved just too short to be useful."

The groundbreaking work by the ANU team was made possible by grants from the UK Wellcome Trust, the Australian NHMRC, an Australian Research Council Federation Fellowship, and by the Australian Government's National Collaborative Research Infrastructure Strategy (NCRIS) to establish the Australian Phenomics Network.

The ANU team brought together experts from around the world to pinpoint the faulty circuit using state-of-the-art genome mapping, DNA sequencing and cell imaging tools. The discovery has been published in the latest issue of Nature Immunology.

Source
Australian National University