I was thinking the same thing. Perhaps the trade-off made by evolution is about saving energy?

In that case it shouldn't be a problem to boost the innate immune system, as long as you have surplus calories to spend. But it could be something else entirely.

It could be just "good enough" as it is. That is, as another poster commented, there is a Th1 or a Th2 reaction. And these in a sense compete. Only one appears to be active.

The current framework of our immune system could go back quite some time. Even to our mammalian cold-blooded ancestors, 200? mya. When I think of cold blooded, I think of creatures able to remain static and at rest for a long time, periods of low-energy usage. So maybe this framework comes from before warm blooded mammals?

And, if it works well enough that people can breed (which used to be 15 years to 30 years old), and if dying after, oh well. Why evolve better? Or maybe too much monkeying has downsides.

Look at sickle cell anemia. Quite beneficial with malaria parasites around, not so much without them.

> shouldn't be a problem to boost the innate immune system, as long as you have surplus calories to spend.

So I'd lose weight too? Sign me up yesterday.

Evolution is not a perfect optimizer.

No but it’s very good. Just upregulating an already existing system is the sort of thing that can evolve very quickly if there’s a big benefit to survival.

Evolution just needs people survive long enough to reproduce. If they get sick afterwards, it doesn't care.

Unless they are contributing to the survival of their offspring.

It can work the other way, too. Your offspring may be more likely to survive if you stop consuming resources once they become viable.

Are you sure that availability of resources was a limiting factor during a large part of human evolution?

ie what has driven human population growth - a fundamental change in availability of natural resources or a fundamental change in how humans exploited them?

I'd argue it's the latter, and that's driven by accumulated knowledge - and before writing - the key repository of that was - old people.

Humans have selective adaptations to reduce resource competition between older and younger members of populations - examples are menopause and testosterone levels.

Part of the reason it benefited us that some but not all people become old is because people require more attention during two phases of their lives. Our biological evolution has prioritized care for the very young over the very old, with respect to a limit on resources (like attention), effectively until the modern age. In some cultures, for instance, those with teeth must pre-chew food for those without, or expected members to engage in ritual suicide at a certain age.

I think it's a mistake ( common ) to view any organism at a point in time as perfectly adapted.

It's like saying cars pistons are designed to wear out - because they do and as the car is perfectly designed ( the mistake ) then it must be for a reason.

Also take menopause - it happens a female has all the oocytes ( eggs ) they will ever have already at birth. Menopause happens when they run out.

What you are arguing is that the number at birth is optimised with a very indirect feedback loop - as oppose to a very direct one of how much resources do you put aside for eggs in terms of maximising number of direct children versus resources used. Occams razor suggests the latter is going to be stronger.

If what you say is true - think about it - old people wouldn't gradually crumble due to wear and tear, they would have evolved some much more efficient death switch. ie Women don't suddenly die post menopause.

The vast majority of human evolution happened in non-humans

Sure - though the tuned behaviour around turning the innate immune system up and down is probably dominated by the more recent part of that long history.

Well, given that the biggest killer of humans throughout most of our history was starvation, I think there's a good chance that's true.

How much accumulated knowledge do hunter-gatherers have?

Which is one theory why grandmothers (post-menopausal women) are a thing

Except humans are a social species and the bands of humans who survived were the ones with the behaviors which kept elders around because of their benefits to our capacity for social learning.

Evolution happens both sides - you and the virus/bacteria trying to live off you.

One of the risks of an always on response, is if something evolves to evade it - you have nowhere to go.

It's why taking an antibiotic at breakfast everyday is not a good idea.

> It's why taking an antibiotic at breakfast everyday is not a good idea.

Eh, the main downside in the short run is that you are killing your gut fauna.

> One of the risks of an always on response, is if something evolves to evade it - you have nowhere to go.

Evolution can't look into the future. (And eg bats are pretty much always on with their immune system.)

> Evolution can't look into the future.

Sure. But yesterdays mistakes can be punished today. ie all evolution happens in retrospect - a mutation haopens - the world tells you after the fact whether that was good or bad. Evolution is hindsight in action. In hindsight - taking antibiotics everyday might have been a bad idea.

> Eh, the main downside in the short run is that you are killing your gut fauna.

Sure - thus increasing your chances for being colonised by an unfriendly and antibiotic resistent bug - which may result in your death - which in hindsight was obviously a bad idea....

The immune system will grow fat and lazy, it will forget how to manufacture anything and be of no use to the rest of the organism.

It’s only an imperfect vaccine — broad immune protection. Evolution probably has come up with a bunch of these.

It's probably because maintaining the immune system at high levels costs more energy.

You probably know that antibiotic use is rampant in industrial livestock. But do you know precisely why?

Antibiotics aren't just given prophylactically to prevent infections; constant low doses actually *increase the animal's size*. The animals can put more energy into growing larger, and spend less on their immune system.

I'm not sure the causal mechanism is completely understood.

Such as autoimmune disorders or other hyperinflammatory disorders?

Graves’ disease, lupus/SLE, psoriasis, type 1 diabetes, myasthenia gravis, Addison’s disease, Hashimoto, Goodpasture, etc.

Yes, i was thinking just this. Having been prescribed multiple immunocompromisers, turning up my immune system sounds terrifying. There's all these supplements and things that talk about boosting your immune system and i get probably most are unrelated, i don't have the time to get a degree in immunology to find out. Zinc does well enough for me, thanks. But if any immune boost started to increase my tnf-alpha or il-23 i'd be on the long and painful road to a terrible death. Or yet another high side effect medication.

> cranking up the innate immune system all the time reduced illness with no downsides

But isn't that what the adjuants that are currently in nearly every vaccine do anyway. That is forcing the triggering of immune response when there wouldn't be none or very little response naturally?

That’s adaptive rather than innate, as the article makes clear.

They’re largely an artifact of civilization, with people living in close proximity to lots of other people, and to livestock. We haven’t had time to evolve for that new reality.

You wouldn't have to do it all the time. Modern humans are much more likely to get a respiratory infection in the winter (I get sick once a year like clockwork). It could be worth stimulating your innate immune system for a few months every year during flu season. Or before traveling.

> If cranking up the innate immune system all the time reduced illness with no downsides, you'd think evolution would have done it already, but it didn't, which makes me think there's probably a downside,

Auto-immune diseases are the downside. There is no way that this ends up being safe or recommended for use outside of epidemic situations or short term occupational hazards.

> you'd think evolution would have done it already, but it didn't, which makes me think there's probably a downside

Couldn’t you apply this logic to any medicine?

That’s not how evolution works.

Also the obligatory, “in mice”.

But evolution is not optimizing for best outcome in terms of health. As Dr Karl said, "Evolution does not have to be perfect, just good enough for you to have babies & get them to maturity".