7 Comments

I really appreciate knowing this. I would have never questioned original antigenic sin until you started talking about it.

Expand full comment
author

I'm glad it is appreciated - thank you!

Expand full comment

So... what about "linked epitope suppression"?

Expand full comment
author

That seems to be mostly associated with acellular pertussis vaccines and given a different name as the proposed mechanism involves repeated exposure / reinforcement.

Typically, "masking" or "trapping" refer to the nuts and bolts behind imprinting - naive B Cells do not see variant antigens because your old B Cells are making IgG that still binds to it (outcompetes natural IgM). Your old B Cells can remodel in terms of which ones expand, like in the "basketball players coming off the bench" analogy - so if you have players on the bench that neutralize the variant, they come off the bench and expand and your naive B Cells don't see the variant antigen (why would you need them to if you have B Cells that can already bind to it?). So this if fine and like I say imprinting is the one column that is going to have a good amount of Y's over N's.

I am not sure if this really applies to aP vaccines since it's a question of different antigens on the bug. Masking says a good anti-tire antibody stops naive B Cells from seeing variant tire; it doesn't say it stops them from seeing windshield wiper. So like I said the term "linked epitope" seems to be specific to that one context, on a first impression.

Expand full comment
Aug 31, 2022Liked by Brian Mowrey

I'm not all the way through this yet, it's going to take a few sessions. But thanks. It's helping me understand some of the terms that get thrown around. Like "imprinting". From what you describe as the process that's a poor term for it. Confusing. But I'm a physicist and we get irritated by unclear language.

Expand full comment
author

"Imprinting" is ok as far as capturing the essence. Initial exposures, by infection at least, initiate a B Cell response in multiple germinal centers and the end result is a "team" of B Cells that correspond to multiple epitopes. When variant viruses are encountered, that team can move players from the bench effectively enough that no new germinal center responses occur (pre-existing IgG outcompetes natural IgM and so naive B Cells remain dormant). So instead of your "immune system" "learning new tricks" it is the B Cell team from initial exposure that autonomously learns new tricks.

A more apt name might be "immune plasticity" because it should have a positive connotation.

But this is not prescriptive - if the B Cell "team" truly needs new players than "the immune system" - new germinal center responses - seeing antigen that old IgG can't outcompete natural IgM for, will make those.

Expand full comment

Nothing is taught about biology being electrical meaning we are electrical beings. Nothing was mentioned about Antoine Bechamp and Terrain Theory. That in itself indicts medical science. What we have is not science. Testing in labs tells us nothing about how things work outside the lab which is where everything lives. Open your eyes everyone, we're being scammed and herded. You are an electrical being. You have electricity. People steal it off you and the projection of what we do on the ground here, is seen on the world circus.

Expand full comment