How the immune system sets priorities - study

When a person contracts one pathogen shortly after contracting another, innate and adaptive immunity must both go to work simultaneously.

  The inner lining of a mouse gut has finger-like projections (white) and harbors lymphatic organs (red) containing germinal centers (green). Viewed with confocal microscopy (photo credit: WEIZMANN INSTITUTE OF SCIENCE)
The inner lining of a mouse gut has finger-like projections (white) and harbors lymphatic organs (red) containing germinal centers (green). Viewed with confocal microscopy
(photo credit: WEIZMANN INSTITUTE OF SCIENCE)

A new study by a team of researchers led by Prof. Ziv Shulman at the Weizmann Institute of Science Immunology Department sheds light on how our immune systems prioritize one infection over another. Their findings could help to develop new therapies for autoimmune diseases such as rheumatoid arthritis and lupus and even change the way certain vaccines are produced in the future.

Published in the peer-reviewed journal Immunity, their study explores the two arms of human immunity. The body's first line of defense is known as innate immunity, and it's activated when our immune system senses viral, bacterial or other invasions.

Our second line of defense is known as adaptive immunity, which includes specific cells and antibodies that are able to fight off the invaders with greater precision and offer longer-lasting immunity. Adaptive immunity takes more time to kick in and therefore comes at a different stage of infection than innate immunity. 

When a person contracts one pathogen shortly after contracting another, such as by consuming food with salmonella while recovering from a flu, innate and adaptive immunity must go to work simultaneously in order to build lasting immunity to the first pathogen – in this case, the flu virus – while fighting off the second: the salmonella.

Experiments using mice led by PhD student Adi Biram determined that secondary infection interferes with the production of antibodies against the first infection. The immune system considers the production of these long-term defenders as non-essential and will instead prioritize defending against the more immediate threat. 

Prof. Ziv Shulman and Dr. Adi Biram (credit: WEIZMANN INSTITUTE OF SCIENCE)Prof. Ziv Shulman and Dr. Adi Biram (credit: WEIZMANN INSTITUTE OF SCIENCE)

However, it's not the salmonella itself that causes this prioritization. What the researchers discovered is that when the bacteria-infected lymph nodes of the mice, a sort of "alarm" went off that alerted innate immune cells known as monocytes to leave the bone marrow where they are produced and move to the lymph nodes in order to destroy the bacteria.

The process causes an oxygen shortage within the lymph nodes. While most immune cells can adapt, the specific subset that generates antibodies cannot survive without oxygen so the cells die, halting the process that creates long-term protection. 

The process as “an either/or situation," Shulman explained. "When you are fighting life-threatening bacteria, you can’t be bothered with long-lasting immunity. Destroying the salmonella gets priority because it’s a matter of survival.”