Only a few vaccines – for example, against polio and rota virus – can be given orally. Most must be delivered by injection. Weizmann Institute of Science researchers suggest this may be, in part, because the training program of the immune cells in the gut takes place under harsh conditions. Dr. Ziv Shulman and research student Adi Biram investigated this process for the gut-based cells involved in long-term immunity using a novel imaging method that captures all of the immune cells’ niches within a single organ.
Their findings provide new insights that may, in the future, lead to the design of more effective oral vaccines. The effective, long-lasting protection we expect from a vaccine originates in a response that is undertaken by immune cells call B cells. Each of these immune cells secretes one antibody molecules that bind a specific target.
Following exposure to a vaccine or invading pathogen, a preparation program selects the B cells with the antibodies most fit to attack the particular threat, admitting them to special training niches within the lymph nodes. There, these cells undergo rounds of division and mutational changes until a pool of finely-honed, “high-affinity” antibody-producing cells is created; these cells persist in the body; providing immunity even to future challenges from this specific threat.
Shulman, who is in the Institute’s Immunology Department; has investigate this process in the lymph nodes that are find in nearly all the body’s peripheral tissues. But the lymphoid organs in the intestines; in addition to hosting B-cell training against pathogenic diseases; also keep the gut bacteria in check; making it difficult to discern each function separately.
And the specialized immune niches within the organs are so small and well hidden, it is hard to study them with the standard methods. He and Biram developed a way to remove and image the gut lymph organs; borrowing the “clear brain” method from neurobiology in which tissue is make transparent and the organ then viewed with standard light sheet fluorescence microscopy.
This method, says Biram, enabled them to capture all of the immune niches in an entire organ and to study how these compartments contribute to the emerging immune response. The researchers then analyzed the gut lymphoid organs from mice that is immunize orally.
“We found that the lymph organs in the gut operate by a different set of rules than those in the peripheral lymph system,” says Shulman. In fact; the gut lymph system does not collect antigens through tissue drainage; as happens in the peripheral lymph nodes; but rather by active uptake of vaccine or pathogen particles from inside the gut.
And if the peripheral system is a “capitalist” one that aims to select and produce the most effective antibodies quickly; the gut system works on a more socialistic principle; at least in the beginning. That is; cell producing antibodies with any level of affinity, at all, are allow to divide and secrete antibodies in response to the threat during the early response. Only later do some with higher affinity gain admittance to the training grounds for further improvement.