For the air we breathe and the microbes that make us sick, the nose is a major gateway. Covered by a unique mucus-secreting tissue with many nerve cells responsible for our sense of smell, curled shelves of bone called conchae warm the air we breathe and absorb moisture before it reaches the lungs. But nasal conchae have a major weak spot – they are not accessible to the antibodies dispatched by our immune systems via the bloodstream during an upper airway infection.
How, then, are we relatively protected from invading microbes and not constantly sick?
When the coronavirus was spreading across the globe, millions of people kept close tabs on the development of a COVID vaccine that could be administered as a nasal spray instead of an injection. It’s not an outlandish idea – after all, several vaccines are already available through nasal sprays. Nasal vaccinations, however, are not effective in a single dose and must be followed up by a booster. Yet, scientists do not yet fully understand why.
An immunization treasure hunt
In this new study led by PhD student Jingjing Liu in Prof. Ziv Shulman’s lab, Weizmann researchers found that antibody-secreting cells migrate to the nasal conchae whenever we are sick or given a vaccination, and from there they secrete antibodies locally into the nasal cavity.
Discovering that T cell migrations are activated in response to vaccines was only the starting point for an intensive search to determine where the antibody-secreting cells go after the differentiation process is completed. “We visualized an immune response in the nasal lymph nodes, but how is it translated into airway protection?” says Prof. Shulman, “...it is possible that this niche environment has other roles beyond the immune mechanism that we identified.”
Beginning their journey in the nasal cavity, some precursor B cells, destined to become antibodies, have the potential to identify pathogens. After identifying vaccine molecules, they divide and differentiate rapidly.
B cells then move from the conchae to the immune system organs close by. Once there, B cells change, aided by a certain type of T cell, to ensure the survival of only those that produce antibodies that are then stored for a period of time to fight a specific pathogen.
One of the team’s key discoveries was that there are not enough T cells in that part of the body to turn B cells into effective antibody producers. This explains why one dose of nasal vaccine is not enough.
“It is possible that this mechanism goes awry when people develop allergies and various autoimmune diseases, so understanding it could help develop new treatments for these conditions,” Prof. Shulman says.
The new findings show that the antibody-secreting cells translocate themselves from the nasal lymph nodes to the mucus-producing glands in the nasal conchae, directly below their external layers of cells, and that they secrete their antibodies into these glands. This immune defense makes up for the blood antibodies’ inability to get to this gateway through the bloodstream. This is not only important in the context of viruses and other diseases; this mechanism also protects the brain and the many nerve endings in that part of the body, which are responsible for our sense of smell.
These antibody-producing cells inside the nasal conchae discovered by Weizmann researchers may help develop new nasal vaccinations and treatments for allergies and nervous system disorders.
