Navigation Links
Understanding immune system memory -- in a roundabout way
Date:11/11/2013

While the principle of immune memory has been known for decades, the exact molecular mechanisms underpinning it have remained a mystery. Australian scientists have now unraveled part of that mystery, identifying the role of a gene called STAT3, which acts as a kind of roundabout, directing chemical messenger molecules to various destinations.

An infection, or a vaccination, 'primes' the immune system, so that when you next encounter the same invader, your body 'remembers' it and quickly makes large amounts of exactly the right antibodies to quash the infection.

Once a cell is primed, traffic on the STAT3 roundabout speeds up enormously, as if the road has been upgraded and the signage much improved.

Primed immune cells, known as 'memory B cells', behave very differently from 'nave B cells', which have never seen infection. Memory B cells act with great speed and efficiency, removing a pathogen so quickly that people frequently remain unaware they have been infected.

Patients with the rare immunodeficiency disorder, Hyper IgE Syndrome, caused by mutations in the STAT3 gene, have a 'functional antibody deficiency'. While you can detect antibodies in their blood, those antibodies are not very good at fighting specific diseases or infections.

Through studying the blood cells of Hyper IgE patients over time, Associate Professor Stuart Tangye, Dr Elissa Deenick and Danielle Avery, from Sydney's Garvan Institute of Medical Research, have gained considerable insight into the STAT3 gene. They recently observed that nave B cells in Hyper IgE patients barely respond to important signaling molecules, whereas their memory B cells behave in the same way as those of healthy people.

The lab members realised that nave B cells need a very strong chemical signal indeed targeting STAT3 to kick-start antibody production. Conversely, memory B cells only need faint signals to generate a huge antibody response. Even STAT3-compromised memory cells from Hyper IgE patients are functional. This breakthrough finding is published in the Journal of Experimental Medicine, now online.

"This study helped explain why patients who have mutations in STAT3 can't generate an effective secondary response to infection," said Associate Professor Tangye.

"STAT 3 directly affects the creation of memory cells, and so while these patients have a few, they are reduced tenfold."

"When people mount a normal primary or secondary immune response, various messenger molecules known as 'cytokines' bind to receptors on the cell surface and activate STAT3."

"Many structurally different cytokines, with complementary roles in antibody production, converge at STAT3 it's literally like a roundabout, showing cytokines which route to take next within the cell."

"This study has shown us that memory cells are much more sensitive to the cytokine signals they receive. They are more robust and efficient, and the magnitude of their response is much greater than that of nave cells."

"B cells fundamentally change their biology between the nave state and the memory state. STAT3 appears to be the key to this molecular rewiring because without it, memory cells cannot form properly."

"These findings explain a lot to me about how immunological memory works, and also throw more light on Hyper IgE Syndrome. They also tell us that if you want to improve antibody responses, there are certain pathways and cell types that can be targeted."

"We can see the future potential to amplify the potency of vaccines, as well as help Hyper IgE patients."


'/>"/>

Contact: Alison Heather
a.heather@garvan.org.au
61-292-958-128
Garvan Institute of Medical Research
Source:Eurekalert

Related biology news :

1. Study amplifies understanding of hearing in baleen whales
2. New genetically engineered mice aid understanding of incurable neuromuscular disease
3. New data improve understanding of breast cancers multiple varieties
4. Understanding why some people have propensity to disease
5. Understanding the RNAi Reagents Market Overlap with Drug Discovery and Therapeutic Development is Critical for Pharmaceutical Leaders
6. Zebrafish could hold the key to understanding psychiatric disorders
7. A trained palate: Understanding complexities of taste, smell could lead to improved diet
8. New understanding of terrestrial formation has significant and far reaching future implications
9. Understanding faults and volcanics, plus life inside a rock
10. Discovery increases understanding how bacteria spread: U of A study
11. Stem cell research aids understanding of cancer
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:3/30/2017)... LOS ANGELES , March 30, 2017  On ... Hack the Genome hackathon at ... This exciting two-day competition will focus on developing health ... experience. Hack the Genome is ... has been tremendous. The world,s largest companies in the ...
(Date:3/29/2017)... the health IT company that operates the largest health ... today announced a Series B investment from BlueCross BlueShield ... investment and acquisition accelerates higi,s strategy to create the ... activities through the collection and workflow integration of ambient ... secures data today on behalf of over 36 million ...
(Date:3/24/2017)... 2017 The Controller General of Immigration from Maldives ... Algeen have received the prestigious international IAIR Award for the most ... Reading ... Maldives ... Abdulla Algeen (small picture on the right) have received the IAIR award ...
Breaking Biology News(10 mins):
(Date:10/11/2017)... ... 2017 , ... Disappearing forests and increased emissions are the main causes of ... year. Especially those living in larger cities are affected by air pollution related diseases. ... most pollution-affected countries globally - decided to take action. , “I knew I had ...
(Date:10/10/2017)... , ... October 10, 2017 ... ... cancer-focused pharmaceutical company advancing targeted antibody-drug conjugate (ADC) therapeutics, today confirmed licensing ... HPLN (Hybrid Polymerized Liposomal Nanoparticle), a technology developed in collaboration with Children’s ...
(Date:10/10/2017)... Oct. 10, 2017 SomaGenics announced the receipt ... to develop RealSeq®-SC (Single Cell), expected to be the ... RNAs (including microRNAs) from single cells using NGS methods. ... need to accelerate development of approaches to analyze the ... "New techniques for measuring levels of mRNAs in ...
(Date:10/9/2017)... ... ... The award-winning American Farmer television series will feature 3 Bar Biologics in an ... on RFD-TV. , With global population estimates nearing ten billion people by 2050, ... a growing nation. At the same time, many of our valuable resources are becoming ...
Breaking Biology Technology: