Immunity system complexity: triggers for initial reactions (Introduction)

by David Turell , Wednesday, May 13, 2020, 19:38 (1437 days ago) @ David Turell

Another complex molecular system:

https://medicalxpress.com/news/2020-05-component-innate-immune.html

"How cells recognize pathogens and alert the immune system swiftly is a fundamental process of high importance for the survival of any species, including humans. A key role is ascribed to so-called adapters—little molecular platforms inside cells where signals from pathogen detectors are integrated for safety and accuracy and conveyed to lasting signals leading to the activation of the major "red alarm" genes, like interferons.

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'The new protein, named TASL, is indispensable for the signaling of so-called Toll-like receptors (TLR) in the endosomes leading to activation of the gene-activator IRF5 in certain immune cells. Sensitive 'tuning' of the machinery is highly important as too much output causes inflammation also in the absence of the pathogen, as occurs in auto-immune diseases. This particular version of the machinery seems particularly associated with disorders such as systemic lupus erythematosus (SLE).

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"In their study, first author Leonhard Heinz and the team, including Boehringer Ingelheim researchers in Ridgefield, undertook a precise investigative work, not taking for granted previous findings on SLC15A4 and the connection to this group of specially located TLRs. They painstakingly determined by biochemistry and mass spectrometry the molecular interactions that involved SLC15A4. This led to the identification of an uncharacterized protein CXorf21, belonging to the functionally orphan genes that are merely numbered and assigned to the chromosome of origin. The gene, like SLC15A4, had been previously loosely associated with SLE.

"The team demonstrated that the interaction between TASL and SLC15A4 was crucial for the localization and function of the TASL protein and could pinpoint the precise involved portions of both proteins. A eureka moment for the understanding of the protein came with the observation that TASL harbors a specific motif essential for the recruitment and activation of IRF5. "After STING, MAVS and TRIF, the new protein TASL is the fourth key innate immunity adaptor functioning as a platform for the encounter of a kinase and a gene activator of the IRF family," says Manuele Rebsamen, CeMM senior postdoctoral fellow and project leader of the study."

Comment: Once again we see a complex set of specified molecular reactions by precise molecules. Since organisms must be able to fight dangerous infections when they first appear in evolution, this mechanism must have been there from the beginning, and therefor designed, since chance is so unlikely to find this series of molecules and its purpose.