Ancient microbial arms race sharpened our immune system but left us vulnerable | Hacker News Reader

Ancient microbial arms race sharpened our immune system but left us vulnerable

sciencemag.org

63 pointspseudolus24 comments

Sialic acids are super interesting, and the biosynthesis of sugars with them on is controlled by a small group of enzymes (20-ish). These enzymes have different tissues and cell type expression profiles, and can catalyse linkage of sialic acids in one of three conformations (linkages on carbons 3,6 and 8).

They’re in every cell, and the biosynthesis pathway limits how many different combinations of linkages you can make. So how exactly is it that these pathogens have often such amazing specificity for particular cellular receptors, if we know they bind sialic acids?

The answer lies in higher order assemblies called clustered saccharide patches, proposed by Varki a few decades ago. This is when the proteins (or lipids) that the sugars are found on have a particular shape, which enhances the binding by the pathogen (or Siglec). They were theoretical for a long time, but right now we have the tools to be able to dissect this, and our lab has had some success finding evidence for this, and we’re using our capabilities to dissect Siglec specificites too.

Also, I find it is massively unsatisfying that SARS-CoV 1/2 don’t use Sialic acids to recognise our cells, when it’s more likely than not to find a virus that binds sialic acids.

TLDR: The human and primate outer cell membrane is covered by a sugar coating (sialic acids) which protects the cells from foreign microbial invasion. Human cells are coated with one type of sialic acid, N-acetylneuraminic acid (Neu5Ac). But apes and most other mammals also carry a different one, N-glycolylneuraminic acid (Neu5Gc). 2 million years ago a mutation in a certain gene led to overproduction in one type while dicontinuing production of the other type.

This abundance of one type of silaic acid sharpened our immune system to specific microbes but since we discarded the other type or silaic acid, left us also vulnerable to certain microbes.

Thank you

Autoimmune diseases are becoming more common[0] and so we will need to better understand them to maintain the health of the population. If the evolution of these Siglecs could be better understood perhaps that would provide an insight into what causes them to go haywire and target our own tissues. I wonder what environmental factors could be at play given that the rise in autoimmune disease is so recent and sharp. Do we for example ever see autoimmune disease in our animal relatives with similar immune systems, e.g new world monkeys?

[0]https://www.technologynetworks.com/immunology/news/amp/autoi...

Likely, we're living much longer, and most other things we'd die from before an ill-tuned immune system due to post-sexual maturity thymus atrophy became a problem aren't killing us as often anymore.

That at least explains the prevalence of old-age related autoimmune problems. Not so up to date with regards to the younger folks or genetics linked ones though.

The rise in autoimmune diseases is probably due to higher inflammation levels due to the trend of steadily increasing levels of sugar consumption and seed oils amongst western societies - same reason heart disease continues to be a killer.

> probably due to higher inflammation levels due to the trend of steadily increasing levels of sugar consumption and seed oils

Any resources where I can read up more about this?

I've got one for the seed oils

http://raypeat.com/articles/articles/unsaturated-oils.shtml

Afaik sugar is not inflammatory though.

> Plants produce many protective substances to repel or injure insects and other animals that eat them. They produce their own pesticides. The oils in seeds have this function.

> I use some of these oils (walnut oil ..) for oil painting, but I am careful to wash my hands thoroughly after..

The fats in nuts are obviously there to poison those who eat it, same as sugar in fruit.

> Cancer can't occur, unless there are unsaturated oils in the diet.

There might be an interesting connection, but I wouldn't take Mr. Peat's statements at face value.

The sugar in fruit is not poisonous and encourages you to eat it so you can carry the seeds to another location but you're not meant to chew or digest the seeds. Nuts are similar to seeds in this way.

>Cancer can't occur, unless there are unsaturated oils in the diet.

This does seem like a dubious statement.

Many plants have seeds with ample sugars, fats, and/or protein, yet no nutritious or enticing exterior. Is the preferred evolutionary strategy falling to the ground and poisoning anything that dares to eat you?

Obviously spreading doesn't work if all of the seeds are eaten, but I've seen walnuts spread far and quite effectively (multiple saplings yearly) - presumably by crows failing to crack a nut, mice not eating some of their gatherings or similar methods.

BTW the fruity part of walnuts is definitely poisonous, as are the leaves and maybe even the wood, but the nuts are fine and nutritious.

Loop up AIP diets

Interesting. I have never heard about seed oil over consumption being an issue.

This. I have an autoimmune. and follow many groups

Eventually people realize diet is the biggest area they need improvement.

Plain Sweet potatoes are my go to for low inflammation food. I do so much better on them.

From the article: "If a woman with only Neu5Ac sialic acids mated with a man who still expressed Neu5Gc, her immune system may have rejected that man’s sperm or the fetus that developed from it. This fertility barrier might have helped divide Homo populations into different species more than 2 million years ago, the researchers speculated."

If it was a single mutation with such a drastic effect on breed ability, how could the mutation have had a chance to spread?

Maybe it beat out its ancestors that had 4 variants instead.

Seems more likely, I suppose. But it would seem hard to maintain a coexisting, yet reproductively incompatible variants.

I'd guess intoleration of Neu5Gc only came in later generations. Article says there were intense adjustments to the immune system after dropping Neu5Gc.

> The influenza A virus, shown in a stylized scanning electron microscopic image

That's a cg render with ultra shallow depth of field like in typical optical microscope. Scanning electron microscopes have depth of field in order of few feet. How can I take rest of the article seriously?

Having worked at a newspaper, someone in web production was likely asked to search a stock image site for "influenza virus" to illustrate the article, and the caption is copied directly from there. In this case, it looks like you can blame the folks at https://www.sciencesource.com/.

It'll be someone entirely separate from the folks who wrote the text.

It's hard to convince folks to read your article without the introductory image (even if it is irrelevant or out right misleading). Sad but not totally unexpected given our short span to focus on anythin in the ocean of "information".

Here you can find the "non stylised" Electron Microscope image from another paper:

https://jvi.asm.org/content/93/19/e00644-19/figures-only

Do you think the stylised imagery has any correlation to the electron microscope image? Which image do you think the stylised one is based on?

This is how the original [0] is described so they probably just went with that and a bit of editing for effect.

[0] https://www.mediabakery.com/MRF0009873-a-stylized-scanning-e...

Reply on news.ycombinator.com