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I feel entitlement-vibes

I feel entitlement-vibes

Posted Jan 30, 2025 11:46 UTC (Thu) by paulj (subscriber, #341)
In reply to: I feel entitlement-vibes by nix
Parent article: FOSDEM keynote causes concerns

Another factor is the imprinting if you keep being exposed to the same antigen. Your humoral immune system works on a form of rapid evolution, where B-cells (which later will produce antibodies, when stimulated) are "trained" and selected for in germinal nodes/centres (GCs). Your B cells go through rapid evolution in the GC, to try adapt to antigen collected in the GCs, with a selection pressure applied (at least in part) by T-cells. Different lines of B cells in the GCs will evolve to recognise different features of an antigen - it's a stochastic learning process. You end up with different lines of B-cells that have been trained to recognise different parts of different antigens _in different ways_.

There is evidence that repeated exposure to the same antigen will lead to this system becoming very specifically trained to that antigen - "imprinting". With rapidly evolving pathogens, with rapidly varying antigens, this is not per se a benefit.

E.g., (and without making a specific point about any particular disease), repeated immunisation with a vaccine that contains (or causes the manufacture of) 1 specific, unchanged, antigenic protein of a pathogen, is likely to lead to a population of B cells with a stronger bias towards that antigenic protein (kind of like doing ML with a large data-set except it's strongly biased to one feature). Yet, if that pathogen evolves rapidly in the wild it is likely to lead to mutations in that antigenic protein so as to evade those immune responses trained to that old version of that protein.

It is probably better to train your immune system with a /spectrum/ of antigens. Not just 1 protein from 1 version of a pathogen that was in the wild 3+ years ago (and has evolved numerous new, slightly different, lineages since). The literature suggests this is the case across a number of diseases, where we have some data on repeat exposure to unchanged v evolved antigens (be they from vaccinations or infection). That is NOT to say there is no value in immunisation by vaccination! But it does suggest there may be /diminishing/ value - even sometimes negative value - in repeated vaccination with old antigens (in the general sense). There is /some/ evidence in the literature this may be the case for ever-repeating covid19 vaccinations (all in the west present a subunit protein of the spike, with a very infrequently updated version of it). In tandem with vaccinations, we all are anyway - unavoidably - exposed to the full pathogen, through minor infections, when it comes to highly infectious respiratory pathogens such as SARS-CoV-2, so we will still get that wide exposure.

Then there are also T-cells, which directly kill pathogens, and also help mediate B-cell evolution. Some will last you pretty much a lifetime, as you say.

Things here are fascinatingly complex. There are many systems and interactions. There are trade-offs. Sadly, clever people on both sides prioritise politics over educating themselves and reading actual scientific information - instead getting their knowledge largely from popular political media, which is nearly always laughably simplified to point of just being incorrect - and that's true be it "Colbert" or "Fox News".

There is far too much knee-jerk idiocy on /both/ sides.


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I feel entitlement-vibes

Posted Jan 30, 2025 11:56 UTC (Thu) by paulj (subscriber, #341) [Link]

Oh, "immune imprinting" and "original antigenic sin" are interesting terms to search for in your favourite tool to google scholarly articles - and then follow the thread of higher-prominence citing articles. There's a body of work on this in immunology predating 2020, and so generally free of the politicised stuff post-20, and it's interesting and informative.

Complexity. Trade-offs. They abound.


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