Comment by rossdavidh | Hacker News Reader

Comment by rossdavidh | Hacker News Reader

So, I'm glad that these researchers investigated the case, and reported their findings, but I am not surprised. It would be odd if our immune system, as had apparently been speculated, became less effective against pathogens that it saw a lot. People who live in low-tech areas with, for example, a lot of malaria, will need to have immune systems that remain vigilant, year after year.

Moreover, if a pathogen is in general circulation, a person might easily be exposed to it many, many times in a few years, as you keep coming into contact with people who have it. I would be surprised if it caused the immune system to no longer respond.

More plausible would be that something about the vaccine itself might become less effective, since it is after all not an actual pathogen but rather a piece of one which we are attempting to "trick" the immune system into treating like a pathogen. I believe the term for this part of a vaccine is "adjuvant" (although IANAImmunologist). Most of the vaccinations appear to be mRNA based, if I am reading the appendix of the Lancet article correctly, so it is interesting to see evidence that this method remains "convincing" to the immune system (n=1).

> It would be odd if our immune system, as had apparently been speculated, became less effective against pathogens that it saw a lot.

That actually can happen. It's called "original antigenic sin" or "immunological imprinting".

https://en.m.wikipedia.org/wiki/Original_antigenic_sin

It's especially prevalent in respiratory viruses. The flu is a well known case. The more flu shots you have (the yearly one), the less effective they become (while still more effective than nor having one).

That only happens in cases where the disease rapidly evolves. Which is the case for COVID, though not to the same degree as the flu, which has its genome split into 8 distinct RNA's which mutate and also get shuffled up when multiple viruses infect the same cell.

> It would be odd if our immune system, as had apparently been speculated, became less effective against pathogens that it saw a lot.

This is how allergy treatments work.

Apparently some infections (at least dengue) are worse the second time.

So it's not an absurd idea.

>This is how allergy treatments work.

But allergens are not pathogens, we are looking at substantially different immune pathways and function (allergens have no lifecycle, let alone one involving host cells).

>Apparently some infections (at least dengue) are worse the second time.

There is some compelling evidence to suggest it is specifically having a low, but not zero, level of antibodies that paradoxically increases the chance of severe infection in dengue fever specifically. Possibly by enhancing dengue's ability to infiltrate cells when it is only slightly coated with antibodies [1]. So even in this rather unusual case, it is not seeing dengue a lot, but rather seeing it exactly once and then seeing it again after several years without any contact that appears to cause this issue.

[1] - https://www.statnews.com/2017/11/02/dengue-second-infection/

I agree it's not an absurd idea. But it would be surprising.

I think there's a lot left to discover about how our immune system misfires to cause allergies, but it is worth pointing out that allergens don't reproduce, so the idea would be that if your immune system has enough exposure it will eventually figure out that it's not a pathogen.

But you're correct, it's not an absurd idea, just would have been surprising if true.

> I would be surprised if it caused the immune system to no longer respond.

I wonder if overfitting to Covid epitopes would cause proliferation of Covid recognition at the expense of other recognition?

Moreover, I wonder if it could lead to overwhelming activation, recruitment, and inflammation in the presence of weakened Covid virus (low dose, environmental background) that would ordinarily be cleared?

This definitely deserves more study.

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