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Our Immune System (berthub.eu)
131 points by sturza 5 days ago | hide | past | favorite | 29 comments





Something article points out, which always blows my mind when I think about it, is that B cells (along with T cells and a recently-discovered neurological cell) are one of only three types of cells which can edit their own DNA. Which is a weird privilege - they are allowed to be different to the rest of us.

Another weird thing about the immune system is that although it is most well-known for it's role in protecting us against pathogens, it actively protects us from cancer on a regular basis. The cancers that do appear in humans are possibly only a tiny percentage of the number that have existed.

The article focusses mainly on B cells. But T cells are a really key anti-viral cell. CD4 T cells coordinate the immune response (B cells included, as well as CD8 T cells, NK cells, innate cells etc etc ). There are a similar number of immune cells in our body as their are neurons, and they theoretically can interact with any other immune cell, communicating in several ways. We are nowhere near understanding how it all works together yet!


As someone recently(ish) diagnosed with an autoimmune condition I spent a good year reading up on the latest papers. We’re still in the fling mud and see what sticks phase of understanding the human body.

> The article focusses mainly on B cells. But T cells are a really key anti-viral cell.

Article about the T cells by the same author: https://berthub.eu/articles/posts/covid-19-t-cells/


I was a little confused on this point. Can an individual B cell change its own DNA, or is it rather that the higher mutation rate means that the set of B cells in the body can be considered as editing its own DNA?

The part of the immune system being described is the germinal center reaction. The 1 million times faster mutation rate only occurs for B-cells dividing in these structures and it's caused by some kind of chemical signaling (the name has slipped my mind). Importantly, it only effects the mutation rate of the thing that codes for the antibody the B-cell expresses, but it has been observed that in this part the mutation is pretty much random.

On average, by the way, there is about 1 point mutation in the part coding for antibodies for every single division in the germinal center. But since the particular mutation is random, I'm not sure I like describing this as the B-cell editing its own genome. It makes it more mysterious than necessary.

I should probably turn this part of my PhD thesis into a set of blog posts once I've defended..."affinity maturation" is a weird and wonderful process.


VDJ recombination is an important part of immune repertoire development

https://en.wikipedia.org/wiki/V(D)J_recombination


B cells also do something called Immunoglobulin class switching to change the structure of antibodies they produce when they encounter their antigen. Different types of antibodies interact with receptors on other cells in the immune system to facilitate the immune response.

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

https://en.wikipedia.org/wiki/Fc_receptor#Fc-gamma_receptors


Yup they splice and rejoin their DNA in specific sites as part of V(D)J recombination (this isn't the somatic hypermutation the article mainly focuses on, which is a B cell specific process). 'Our' gene editing tools (CRISPR) were not designed by us, but come from nature, so maybe not surprising!

A very good start to the description of the immune response. One of the most important aspects of everything is that our immune system has to make two distinct determinations about any object it encounters: is this object _foreign_ (thus not made by our own body), and is this object _malicious_? The interesting aspect is how long we too as a community to realize the second requirement exists and is extremely important. The first suggestion that we might have a system to independently determine whether an object is pathogenic was only made in 1989, which is very late for such a fundamental discovery indeed. Whether it's a virus or bacteria, our immune system has to primarily ascertain that it's pathogenic before it can do anything about it.

Importantly, when the immune system goes haywire like it does in Covid, it's because of some fuckery with this system that is at the root cause more often than not.


Isn't anything not antigenically compatible considered eligible to be attacked by the immune system?

Hence transplant rejections.


Indeed, they are but much more slowly and not in the same way. Without innate engagement the response is much mellower and uses different mechanisms than you would expect in an infection. Also half the immune system won't be involved!

I don't quite follow how a non-antigenic match (without suppression) would have anything but an innate response.

Am I "captain obvious" in pointing out that one of the viruses is a bacteriophage?

They actually help us (Eukaryotes, broadly) a lot in containing the spread of bacteria. Maybe in the future our only help in dealing with multi-resistant ones (because of our mindless use of antibiotics), which in comparison is a more scaring prospect - several orders of magnitude higher - than this novel type of human betacoronavirus meticulously detected by millions of non-standardized (temperature (annealing, denaturation), number of gen-sequences, # of cycles) RT-PCR-Tests daily, worlwide ...


Phage can pack host DNA into their capsid which can promotes the spread of antibiotic resistance genes.

I've heard about that, thanks for pointing that out. It can get quite complex when you begin to consider a main mechanism in antibiotic resistance: information flow between other species of bacteria (horizontal gene transfer) + Viruses as significant boosters in evolution with their superpower in living systems to "easily" modify/add huge chunks of DNA/RNA.

Just a side note - I am watching Ninja Nerd on Immune System https://www.youtube.com/playlist?list=PLTF9h-T1TcJj4AOPCxGxO... and it is great! I usually prefer text - but the visuals here really improve memory.

Viruses cannot reproduce independently, they need our help. And our immune system makes this very hard, as aptly explained in this excellent xkcd comic:

I feel like that really is a terrible take on what that comic shows. Based on those two lines, I was expecting the comic to be about how viruses take over a cell and use its own internal structures to turn it into a virus manufacturing plant until it finally explodes and dies, releasing these invaders into the system.

It doesn't show that and it also doesn't really show much about the immune system. It mostly talks about how hand washing and social isolation are effective barriers to the spread of disease, which is something I'm a big believer in but has nothing to do with how our immune system works.

Also also (a thing I said some hours ago elsewhere on HN):

... "the immune system" doesn't really mean a specific set of organs like "the circulatory system" or "the digestive system" means a specific set of organs. It's just kind of a catch phrase for "how the body protects itself" and it's not really that well understood or explained exactly that happens.

https://news.ycombinator.com/item?id=25167263


I love the cognitive dissonance most people have. I'm not implying there's anything wrong with this article -- only that there's a lot of contradictory information people like to believe.

> "your immune system is probably 99.9% effective" > "death rate of 10%" > "deadlier than some strains of the flu" > "safe than some strains of the flu"


How can there be nothing wrong with an article containing contradictions? ;)

Those aren’t contradictory though. It’s not the 99.9% of the virus that your immune system neutralised that kills a patient with severe COVID-19, it’s the other 0.1%. Deadlier than some strains of flu doesn’t mean deadlier than all strains of the flu.


AFAIU (not a doctor): Usually it is not the 0.1% of virus that kills severe covid patients, but the massive carnage and collateral damage from a prolonged battle of an inappropriate immune response (imprecise, slow, escalating..).

I don't see the contradiction. There are so so many things that our immune system eliminates for us every day successfully without so much as noticeable inflammation. It's probably higher than 99.9% of things. This coronavirus is not one of them for many people, neither is the flu. Of course we only talk about the things that actually cause noticeable harm, but that's just availability bias.

Corona deaths are heavily weighted to the elderly and sick who have weakened immune systems.

To a healthy person the article is accurate.


Our immune system hat to activate Tcells + Bcells + IgM + IgG to kill the Virus

Our immune systems are only 99.9% effective? I'm scared, we should lock down the economy, ban church (protests & riots are fine), and mandate face coverings and gloves. Who cares if millions starve [0] as long as less than 0.1% of the population doesn't have complications or die from COVID-19?

[0] https://www.wfp.org/news/wfp-chief-warns-hunger-pandemic-cov...


0.1% of the population is a big number. If we had some mechanism in place to prevent starving, would you be keen to save lives?

Right! .1% is less than cancer and heart disease and innocent people killed in the middle east wars but still more than the flu!

Yeah we do actually. The solution is to increase the economy so people can get jobs to eat food.

The cost to life, combined with sick leave due to illness, long term sequelae of the disease, medical bills and vulnerable people choosing not to do the things they did before, altogether means that the economy will be impacted lockdown or no lockdown. It's a matter of degree and depends what kind of lockdown we're talking about.

Agreed 250,000 dead vs 100 million people in poverty.

The choice is pretty clear to me.




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