Adult immune systems ‘remember’ germs to which they’ve never been exposed (2013) | Hacker News Reader

Adult immune systems ‘remember’ germs to which they’ve never been exposed (2013)

med.stanford.edu

259 pointsakbarnama99 comments

I grew up on a farm. It was common knowledge that when a calf, or a lamb was born they needed to get that first milk from their mom. The first milk looked different and was called colostrum. Colostrum contained a large assortment of antibodies from the mother that were transmitted to the newborn. If there was some health issue, the mother died or the newborn couldn't drink, we had colostrum in the freezer. If we didn't give it, the odds dropped dramatically of the newborn making it more than a few months.

So, yes, mammals, including people, get immunities to germs they have not been exposed to.

This reminded me of neonatal lupus. Lupus is an autoimmune disease where your own antibodies attacks your tissues. In neonatal lupus, the newborn is born with lupus ... because materal autoimmune antibodies are able to cross the placental barrier. So the newborn 'inherits' a lupus condition, which usually self resolves within a month once the maternal antibodies have disappeared. https://rarediseases.org/rare-diseases/neonatal-lupus/

This is presumably applicable to other maternal antibodies, which may give immunity against germs the infant has never been exposed to. However, this is a 'temporary' immunity, and distinct from the adaptive immune responses associated with 'immune system memory'.

Exactly. They typically give pregnant women a Tdap booster in the 2nd trimester. The mother develops an immune response and she transmits those antibodies to the baby. When the baby is born, they have some temporary protection against those diseases, but as you said, it only last a month or two.

My understanding was that breast milk (at least in humans) gave the baby antibodies, but not the ability to create those antibodies. So, the effect wouldn't last.

But still I would imagine that such antibodies would be exponentially more valuable in the earliest moments of life, where it’s likely that the newborn fist comes into contact with the mother’s fecal material and all of the bacteria living on our skin.

Those are (mostly) good bacteria though.

Some theorize the baby needs the mother's poop, to start it's own digestive microbiome. It works that way in other species, but I don't know if it's more than speculation for humans.

You also need a skin microbiome, but you can get that later.

I have heard reasoning that c-section babies could benefit from having some given to them.

Humans produce colostrum early after birth as well. There's a practice of saving it if the mother produces enough milk in case the newborn later has an illness and could use the antibody boost.

That’s correct - one of the proposed treatments for coronavirus is synthetically generated antibodies for seriously ill patients; it won’t teach the immune system as you said but reduces viral load.

This is what I believe to be the case too - so-called "passive immunity" gained by just having their mother's antibodies from either breastfeeding or even earlier via the placenta (at least for humans - as I understand it not all mammals do it via the placenta?). Eventually I think this protection wears off, but can be topped up with further breastfeeding, or eventually the baby starts to generate their own antibodies

Those are IgA and IgG antibodies that are being transmitted from mother to child. They're effective for a period of time until the child's immune system develops but do not confer lifelong immunity as the child's immune system creates no memory from it.

There might be other forms of immunity conferred as well. Antibodies provide immediate immunity even before the younglings immune system gets up and running. There's definitely some sharing of immune cells in the womb, who's to tell what else happens there with a long-term plan?

Anything might be true, but as far as what's probable, I'm not following your logic.

Colostrum also happens in humans. It's different from a regular milk

Um yes. Was surprised to see colostrum discussed in the context of cows and not just humans in general. Every parent should be aware of this fact.

The antibodies in colostrum don't make the animal or human immune in the usual sense of the word - the body is able to generate an immune response to a foreign substance.

It's more similar to therapeutic use of antibodies. Once the colostrum is gone, so is any protection against infection.

Thanks for sharing this, that got me reading:

https://en.wikipedia.org/wiki/Colostrum

and the article from 1961

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1359530/?page=1

which quotes "first noted by Ehrlich in 1892" and "examined in detail by Howe in 1921."

Similar is true of human births: natural vs C-section.

https://health.howstuffworks.com/pregnancy-and-parenting/pre...

https://sciencenordic.com/birth-c-section-children/giant-stu...

Also, if we want to be pedantic about it: way more than half the cells that make up a fertilized zygote are from our mother. Those cells are a living part of her body until the zygote is fertilized. The particular egg might not be fully formed at disease exposure, but it's part of her body just like any other cell.

Apparently, the science backs this up. This paper shows that the mortality of calves decreases if they get colostrum. https://www.ncbi.nlm.nih.gov/pubmed/26995131

Has anyone tried pooling the first milk from different cow moms?

So it is even more frustrating, that mothers were encuraged for a long time, to not breast feed at all and rather use the artifical, sterile milk, because it is healthier. Fortunately the world moved largely beyond that.

How on earth could millions of years of evolution possibly compete with Nestle et al "science"? Did I only say millions? I meant: hundreds of millions, silly me.

Perhaps evolution needs a better advertising budget.

That's like saying we'll never build a device that moves faster than we can run because evolution produced perfect locomotion for us. Or that we'll never be able to communicate further than we can yell, because evolution produced strong lungs for us.

There are plenty of cases where evolution failed. Allergies for instance... our own immune system reacting quite imperfectly to a harmless substance. That doesn't sound like pinnacle of evolution perfection to me.

There is a time that science wins and a time that natural things win. What if science added those antibodies to the formula? What about people who are unable to breast feed.

Allergies are a good example, because as far as I know, they exist mostly in our civilized society and from what I remember, mainly those suffer from it: who were not (enough) breast feeded and were kept in a sterile area as a kid and not in the mud outside.

But in general, yes, we can and could improve with technology on many things. But mostly only things we understand. A car is a very, very simple thing, compared to our bodies, our digestion system, immune system, cell growth ... And our bodies need very complex "material" to grow, as adults not so much, as babies. And mother milk is optimized and can dynamically change to adopt to the need of the baby. It was blind arrogance and yes, profit thinking, to assume a simple formula is better.

I fully agree. My point just being that declaring evolution the victor because "of course, it has had more time" is clearly not always the case.

But even aside from allergies, there are plenty of examples of doing things better than evolution. "I just leave ticks on my body, because hundreds of millions of years of evolution means my body will know how to get rid of them better than I could."

I found, that my body probably has deep instincts to feel, find them and remove them, without even thinking about it.

(there are lots of ticks in my area and I spend increasingly time outside, as a child I was mostly saveguarded from them)

(meaning I scratch myself without thinking or noticing and suddenly have a tick in my hand)

Trains and telecommunications are auxiliary; you walk to the train station and you talk into your phone. For breastfeeding it would be akin to using technology to aid the process, e.g. breast pump, refrigeration.

Allergies are likely an example of our ever evolving physical world, within a few generations the developed world has gone from days spent toiling in the fields to the sterile existence of modern cities, moving from one air filtered compartment to the next.

You may find the hygiene hypothesis interesting - the theory that the incredibly sharp rise in allergic diseases in developed countries is due to no longer being exposed to the types of bacteria that we had during most of evolution.

One example is that allergy rates in Finnish Karelia are much higher than right across the border with Russia, even though the populations and environment are otherwise very similar.

When you're thinking that science won sometimes it's nothing else but a sponsored think-tank and a big marketing campaign that made you think so. Just saying.

Sometimes. But planes being faster transportation than peak evolution (even among other species, not just humans) is not just "think tank".

Blanket declaring evolution as the victor all the time because it has had hundreds of millions of years head start is clearly not always true.

I get your joke, and it's not advertising but lobbying by the large corporations who make baby formula a recommended thing, eg sponsor a thinktank etc, and it's always 100% profit motive. Maybe we should get them off our backs and be aware that most of their products may be worse for us. And ideally change the mechanisms by which they are controlling the government. It's a tough fight because they are organized and have money and we aren't organized and our efforts need to be tenfold.

Maybe you're right in this instance, but your reasoning is fallacious.[0]

What are your feelings on vaccines, pacemakers, and appendectomies?

[0] https://en.wikipedia.org/wiki/Appeal_to_nature

I'm not sure calling me right in this instance is the best start to an authoritative refutation of my thesis.

I am not appealing to nature (please read the article you linked to) I'm appealing to evolution.

I have had my jabs, including malaria, small pox, MMR, and tetanus at least. My Dad has a pacer. The appendix is a funny one because recent research indicates that it might simply act as somewhere for bacteria to accumulate ie a sort of biome generator or refresher, rather than simply being a hangover from something else. Given the way evolution "works" it seems to me that there was an additional useful function that the vestigial appendix carries on doing that means we still have them.

Evolution does not use a drawing board and beautifully rendered isometric drawings and a series of briefings before getting marketing involved. If it works it stays, if it changes a bit and still works and the owner happens to procreate, it might stay. If they die too early it might not stay. Rinse/repeat. Genes (selfish or generous), structures and amalgams and who knows what else, changing and morphing, evolution is a process that should not have a name because it isn't really a process that starts from A and goes to B. It starts from A and might happen to hit L which is quite close to B, which is nice. The biggest problem is that us humans like to slap a tag or a name on things to contain them and then misuse those names rather badly. Hence we get "intelligent design". Evolution is far more fascinating and sophisticated than anything that "intelligent design" could possibly come up with, whilst being far less sophisticated than "ID" - yes I am aware that is a tautology but it seems appropriate. Funnily enough, intermediate steps in eye development have been sighted in the wild.

I'd have added cancer to your list for a proper challenge.

"...memory CD4s proliferated and otherwise became activated in response to exposure to certain components of the influenza virus, but also to epitopes of several different bacterial and protozoan microbes. This cross-reactivity could explain why exposure to common bugs in the dirt and in our homes renders us less susceptible to dangerous infectious agents."

So the CD4 is a key activated to fit a particular lock, but given the imperfections of locks it fits a random assortment of others too. As we build up a keychain of these we have a better chance to fit any random lock.

But why doesn't the larger keychain also increase the chances of auto-immune diseases when they happen to fit our own locks? Or increase inflammation from other benign microbes it fits? Seems like the metaphor needs work.

> But why doesn't the larger keychain also increase the chances of auto-immune diseases, when they happen to fit our own locks?

The process that generates immune cells tests them for autoimmune reactivity and aggressively culls ones that are.

Could you provide the name for this, or something I could search for? This is fascinating.

Look up the function of the thymus in T-cell development and selection.

https://en.wikipedia.org/wiki/Thymus#Function

The term is "Central Tolerance".

The Thymus (Which someone else mentioned) effectively checks the following:

(1) Does the cell react to an antigen (Foreign particle) [β-selection]

(2) Does the cell still work with the immune system (Can it bind to the cells it needs to bind to once it finds the antigen) [Positive Selection]

(3) Does the cell recognize only foreign particles and not the body itself [Central Tolerance / Negative Selection]

Sure, but it doesn't always work :(

I had the misfortune of blowing out my right knee and acquiring a chlamydia infection ~simultaneously. And then developed acute rheumatoid arthritis. Which has progressed, albeit slowly, ever since.

So it goes.

You do get autoimmune diseases this way.

The thyroid does a good job of filtering out new immune cells that attack the body, but sometimes you will get an infection where the targeted protein mimics a body protein. When that happens, you're stuck with an autoimmune disease.

Example: https://en.wikipedia.org/wiki/Reactive_arthritis

I think you meant thymus not thyroid.

Yes, you're right. My bad.

The hygiene hypothesis might play a role here. Early exposure to certain pathogens could have a protective effect against autoimmune disease.

https://en.wikipedia.org/wiki/Hygiene_hypothesis

I may have this wrong, but this can also lead to certain allergies.

https://www.youtube.com/watch?v=kLC0cX3rAX0

Could someone add 2013 to the title? I just spent 15 minutes thinking I must be a genius because I had already figured this out. Now I realise I read about it already.

I agree, bit confusing. I never read about it until now.

William Petri is a wonderfully appropriate name for a professor of infectious diseases.

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

love nominative determinism

There’s a term for this!

The orthodontist that adjusted my siblings braces was named Dr. Hurt (or some homonym) and I’ve observed similar many times since.

If you accept few will, it's an aptonym.

I don't have a choice but to accept free will :)

Yeah, I assume they're all really aptonyms, but I think the other term is more fun

My orthodontist's name was Dr. Link. Nice, but Dr. Hurt would have been more appropriate.

I met peoplw working un financial jobs with last names like Cash and Price.

Don't dish it out...

Admire the attempt but this just didn't really make much sense

It's so agarvating when puns miss their mark.

heh, normally how these friendly call-response threads work is someone either yes-and's the attempt [1] or ignores/downvotes it. Just because we're on HN, that doesn't mean puns need to be critiqued -- even if they are agaravatingly bad :)

[1]: https://en.wikipedia.org/wiki/Yes,_and...

It kinda does, though.

I like that HN has a very high bar for humor, and cracks down on soft-pitch puns which are an attempt at a long chain of groaners.

Reddit exists, and if you like that, you can get it on Reddit. Here it's just noise. We have other bad habits ;)

Here you have to make a plausible argument that the expert who spent their life studying something has no idea what they're talking about and you somehow know better, or manage to one-up the parent who just did something like that with some exceptionally high-grade sophistry.

So I do not understand much about biology but could this effect explain why we seem to have so many people test positive for anti-bodies on COVID-19 tests, compared to other forms of testing?

Likely not, the more likely explanation is asymptomatic cases. There is a possibility of false positives and that could be driven by something like these nonspecific antibodies so that's why I say "likely not" vs "definitely not" and the answer to whether it "could" is yes, but whether it "does" I personally I think asymptomatic cases are the more likely explanation

I don't think CD4 cells are the same as antibodies, right? I assume that when we test for antibodies, we're not testing for CD4 reactivity...

I understood, that the false positive antibodie tests, come from different antibodies against different corona virus or just the flu, because they are too similar.

Only if the person tested is more than 100 years old (ie spanish flu antibodies)

That was an influenza virus, this is a coronavirus they are completely different. But to your point, there have been numerous flu pandemics since 1918

The Spanish flu was a totally different disease though.

“It may even provide an evolutionary clue about why kids eat dirt,” said Davis. “The pre-existing immune memory of dangerous pathogens our immune systems have never seen before might stem from our constant exposure to ubiquitous, mostly harmless micro-organisms in soil and food and on our skin, our doorknobs, our telephones and our iPod earbuds.”

Have there been studies on the effects of being too clean? Will short term fear (e.g., Covid-19) hurt us in the long term?

Would epigenetics from past ancestors explain this? [0]

[0] = https://www.scientificamerican.com/article/fearful-memories-...

No. The article says newborns don't have these activated CD4 cells.

Not on the article but...my understanding is that we have genetic material which has these encounters in it and so it’s transmitted over generations. If it does help or not or even if it manifests at any point and creates antibodies is out of the scope of what I know. However, the epigenetic activation is dependent on many factors.

article doesn't provide any citation to the article it is summarizing...

https://www.cell.com/immunity/fulltext/S1074-7613(13)00052-6...

Antibody production in vertebrates is an amazing example of an extremely efficient directed evolution system within our own tissues.

There is some interesting work being done to mine antibodies from people who have recovered from diseases and use those as a therapeutic medicine. Worked great for Ebola, would also work for COVID-19, but scaling production is really really hard (maybe some schlep blindness there)!

If I recall correctly, they pretty much put the gene for the anti-ebola antibody into a plasmid in bacteria, then vacuumed those bacteria into tobacco, which mated with the tobacco, which caused over-expression of the antibody. Then, you grind up the plant, and purify the protein.

I'm interested in trying that out with my own blood - effectively making open source antibodies for different diseases. I also know a few folks working on DNA vaccination, which could have an interesting intersection.

How on earth do they know for sure someone has never been exposed to a germ? Couldn’t it just be the antibodies were from very limited exposure?

Can anybody recommenf two good books on immunology? One clear introductory and one rearch level detailed?

I can only recommend one, but very good: How the Immune System Works by Lauren Sompayrac https://www.goodreads.com/book/show/940153.How_the_Immune_Sy...

(2013)

How is this relevant? I'm not into this field. The article is only from 2013. So I can only relate it to Covid-19.

Thankful for any response

I'm thinking Bloom Filters.

Could partly explain why it seems like covid-19 isn't hitting developing nations as hard. They have more antibodies to other viruses. There's also the theory that the tuberculosis vaccine (mandatory in many developing nations but not in developed ones) helps too, and there are clinical trials going on to confirm that.

There's an absence of evidence that this is actually true. Tests are in short supply even in places with their own biotech industry; countries which are reliant on importing tests have no accurate picture of what's happening.

Ecuador is an example which has crossed my radar: ~10,000 confirmed cases, but overall death rates are way up and they're digging mass graves.

We would all love to believe that heat and humidity will blunt the spread of this virus, but I'm not seeing nearly as much evidence of that as I would like.

Ecuador is actually one of a very few number of developing nations that doesn't seem to mandate TB immunization. Iran didn't start it until the 1980s.

That said, I agree there is an absence of evidence... It's all speculation at this point.

Most countries don't do TB immunization, they use vaccines only in specifically developing countries. Developed countries use antibiotics generally.

Actually most countries in the world do immunize against TB. And developing countries in particular overwhelmingly do. The US doesn't mandate and most European countries have stopped.

http://www.bcgatlas.org/

An interesting observation about that map is that there is a high correlation between countries that stopped BCG vaccinations and high fatality rate from Covid-19. However, Australia is one of the countries that stopped doing BCG vaccinations but it does not have the high fatality rate of western European countries. What's going on there?

Idk. There's so many confounding factors. I don't know when they stopped the vaccination, but maybe it was recent enough that the vulnerable (elderly) did actually receive the vaccination? Maybe temperature does matter. Maybe they're just behind on the curve. We can only wait and see as more clinical data becomes available.

That may be true today but in the past, not so much. E.g. BCG was given to all non-reactive children in the UK between 1953 and 2008.

My impression is that it's being attributed to the smaller international travel to Africa in the first place, and then that all stopping when the rest of the world locked down. There are some pretty wrenching predictions for how they'll go when it does start spreading, if that's correct.

It's also warm and wet in many developing nations. Seen a couple pieces suggesting COVID is relatively heat-phobic.

Would also jive with seasonality of the flu...

That idea of flu season seems a distinctly North American notion. Flu season in Thailand is June to October, which coincides with rainy season when it is hot and very wet.

I graphed death rate by absolute latitude for countries with more than 1000 cases, and there is a clear trend. There is a bulge in the middle latitudes, and dips toward the lower and higher latitudes. My guess is the virus doesn't do well in hot climates, and people don't congregate much in very cold climates.

It’s the spring in the northern hemisphere, it’s not cold anywhere in the US or Europe. I don’t see how your conclusion is relevant

Yup not cold at all here in Indiana. Please disregard the snow that we had earlier this week...

Lol. It's quite difficult (misguided) to generalize about an entire country!

Sounds plausible. It may be premature to assess the relative impact of covid-19 in those nations. Hopefully you're on to something though...

I don't buy the BCG thing. For one, they count France as one of the countries that don't vaccine and where covid-19 is hitting hard. While the latter is true, the former is... only technically true now. France stopped vaccination, but it was mandatory for school children between 1950 and 2007. So people up to 80 or probably more are vaccinated.

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