Immunity system complexity: control of reactions (Introduction)

by David Turell , Friday, February 03, 2023, 18:25 (449 days ago) @ David Turell

Very necessary as autoimmune mechanisms can be very damaging:

https://puraplyam.com/puraply-am-overview/

"The signaling molecules of the immune system should trigger a response only where necessary. To prevent a life-threatening spread to the rest of the body, connective tissue can absorb these molecules like a sponge.

"When the T cells of the immune system communicate, they do so with the help of cytokines. An important member of the cytokine family is interferon-gamma—a protein that activates the body's defenses, particularly in the fight against viruses and bacteria.

"Over the course of evolution, the human body has developed a variety of strategies to prevent the immune response from overshooting its mark. Another important mechanism has now been discovered by a German-French research team led by Professor Thomas Blankenstein, head of the Molecular Immunology and Gene Therapy Lab at Berlin's Max Delbrück Center.

"In a paper published in the journal Nature Immunology, the scientists explain how interferon-gamma uses four amino acids to bind to the extracellular matrix of connective tissue, which forms a web between individual cells and thus mediates intercellular contact. The study's first author, Dr. Josephine Kemna, explains that this binding prevents the cytokine from spreading throughout the entire body and triggering dangerous immune responses.

"When the amino acids required for binding are lacking, she says, the result is a serious impairment of the body's defenses. Kemna was a member of Blankenstein's team from 2017 to 2022.

***

"The researchers started out using a mouse model developed by Kammertöns, which allowed them to regulate the concentration of interferon-gamma that was produced. "We were already able to determine from this model that interferon-gamma becomes toxic very quickly, and that animals with high concentrations of this signaling molecule in their blood fall ill within a few days," explains Kammertöns.

"Biochemical analyses also revealed that once the protein is secreted via the T cells with its four positively charged amino acids, it binds to the negatively charged extracellular matrix—namely, to the molecule heparan sulfate.

"'This ensures that interferon-gamma is retained locally, and prevents it spreading throughout the body," says Kammertöns. However, given that the structure of heparan sulfate differs depending on the tissue, cell type or even cell state, the ability of connective tissue to bind interferon-gamma can also vary, adds Professor Hugues Lortat-Jacob of the Université Grenoble-Alpes, who was also involved in the study.

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"'In my view, it is clear from our research that our immune system has developed highly potent mechanisms to keep its own defenses in check," says first author Kemna. If these mechanisms fail to work properly, she says, the immune system can end up damaging its own organism due to the toxic effect of certain molecules as they continue to spread.

"'The mechanism we have uncovered shows that evolution has ensured toxic molecules generally act only where they are needed—that is, where the T cell recognizes a virus-infected cell."

***

"'Over the course of its evolution, the immune system has developed increasingly powerful weapons in a sort of arms race against pathogens," summarizes Blankenstein. "Our work has uncovered a new mechanism that acts a counter balance to this arsenal of weapons without reducing the efficiency of the immune response—just four amino acids in interferon-gamma prevent infectious diseases from causing many more deaths."

It therefore makes sense going forward to gain a better understanding of the exact details of "the interaction between interferon-gamma and the extracellular matrix."

Comment: the exactly perfect amino acids are used. How does a naturally produced evolution find exactly what it needs? It certainly suggests a designer at work.