[HN Gopher] A physical wiring diagram for the human immune system
___________________________________________________________________
A physical wiring diagram for the human immune system
Author : bookofjoe
Score : 304 points
Date : 2022-08-08 02:07 UTC (20 hours ago)
(HTM) web link (www.nature.com)
(TXT) w3m dump (www.nature.com)
| hungryforcodes wrote:
| This is a REALLY great paper. I'm assuming if you took the time
| to look up and learn deeply about all the stuff you didn't know
| that you read -- you'd be extremely knowledgable about the human
| immune system after. It's like reading a very complex book. Take
| a few weeks or months to really understand and absorb it all.
| fiftyfifty wrote:
| Someone else in another thread on here recommended the book
| "Wetware: A Computer in Every Living Cell" by Dennis Bray and I
| really enjoyed it. The idea of looking at complex protein
| interactions as logical circuits kind of makes sense as we try
| to map out the complexities of Biochemistry. For anyone looking
| for an easier introduction to the concept I can recommend the
| book.
| beckerdo wrote:
| I am reading "Immune: A Journey into the Mysterious System That
| Keeps You Alive" by Philipp Detmer (https://www.amazon.com/gp/pro
| duct/B08XTNHRR5/ref=ppx_yo_dt_b...). It is a great book for the
| layman, and explains a number of processes in simple and lively
| analogies. My understanding of the immune system increased
| greatly.
|
| However this paper of all the interactions is at a higher level.
| I could just barely relate it to what I know. As an engineer I
| appreciate the presentation of the data and the amount of thought
| that went into it. I will have to study the paper more.
| Hedepig wrote:
| I purchased the audiobook, great listen
| flobosg wrote:
| In case you missed it, here's the interactive atlas:
| https://www.sanger.ac.uk/tool/immune-interaction/immune-inte...
| vavooom wrote:
| Great use of a Shiny visualization here - wonderful way to
| communicate these results
| wiz21c wrote:
| Dunno, tried it. It's painfully slow and the charts labels
| are all crammed, it's unreadable. And I didn't see any
| obvious "zoom" button... Maybe my browser ?
| flobosg wrote:
| The "save plot image" link allows you to download a full-
| size figure that's more readable.
| teruakohatu wrote:
| It is being hit by HN. Shiny apps are often quite resource
| intensive, because they are doing maths heavy computations,
| but under normal usage it would run at a decent speed.
| lamename wrote:
| The Precision-Recall plot on page 17 caught my eye (Extended Data
| Fig. 3a). Specifically the grey area.
|
| "...grey shading indicates the valid range between perfect
| performance and a random classifier."
|
| What's with the diagonal cutoff at the bottom of the plot? I
| understand where the dotted line comes from, but I expected the
| grey shading lower bound to stop at the dotted line entirely.
| SnowHill9902 wrote:
| Feynman's first assignment required him to study the nervous
| system of cats. So he went to the librarian in the biology
| section and asked her if she could give him a map of the cat.
|
| "A map of the cat, sir?" she asked, horrified. "You mean a
| zoological chart!"
|
| "From then on there were rumors about some dumb biology graduate
| student who was looking for a map of the cat.", wrote Feynman in
| his book Surely You're Joking Mr. Feynman.
| rob_c wrote:
| Whilst interesting, I'm left wondering. Why is it so hard to get
| a straight answer of what this achieved.
|
| Just to note I'm not bashing the work here (it appears solid
| unlike a lot of papers from a lot of fields). I just assume I
| must not be the target audience (which is a little odd for
| nature) as I can't easily see what the main takeaway from this
| should be. I'm not expecting an 'explain me like I'm 5', but a
| short abstract-ending paragraph on what the research has achieved
| would have been nice.
|
| Unfortunately my takeaway otherwise is "thing is complex", "did
| complex machine learning", "made a thing which approximates
| reality". Made a model of it again in the lab based on this.
| Therefore this means new therapy for??? (this last line is what
| makes me pause and wonder is this here for grant/committe money,
| or just to claim this was part of understanding/curing lupus in
| 10 years?)
|
| I'm all for trying to classify different interactions into groups
| (even if that makes sense) and tring to understand the immune
| system as a whole.
|
| What (if anything) does this contribute to our current
| understanding other than being a first attempt at framework to
| classify a complex system? (not complaining, that in itself is a
| reasonable goal).
|
| If it is practically a first attempt at this. Why don't they say
| so?
|
| If this is one of a hundred similar models what makes this one
| better/special?
| w10-1 wrote:
| > If this is one of a hundred similar models what makes this
| one better/special?
|
| There aren't any similar models. The complexity of the immune
| system has defeated any systemic model. In most cases, even the
| simple cascade from a single interaction is not modeled.
|
| Most importantly, this is an *experimental* model: it
| simplifies the complexity by focusing on a narrow range of
| interactions that can be modeled in-silico and validated
| experimentally, but whose collective behavior can *also* be
| modeled and validated -- and, most importantly, tied to
| systemic outcomes, of health and disease.
|
| It defines a waltz of truth, that could be the fashion for
| decades.
| lake_vincent wrote:
| Holy moly, I don't know anything about the content, but this is
| straight up data science porn. Those visuals are stunning.
| [deleted]
| yosito wrote:
| As someone who struggles with some vague immune system issues
| with more questions than answers, I was shocked at how much
| knowledge of the immune system is presented here. I was
| immediately curious about how I can apply this knowledge to help
| me understand my own immune issues. Unfortunately, I don't know
| enough about biology and chemistry to understand much of this.
| But I found this bit near the end encouraging, and a helpful
| summary of what is presented here:
|
| > More broadly, the integrated approaches that we pioneered here
| for disentangling the immune system provide a framework for
| future systematic investigations ... Our analysis and the methods
| that we developed provide a template for future studies looking
| at physical cell wiring networks in detail. From these combined
| approaches, we may finally begin to disentangle cellular circuits
| in immunity and beyond, bridging from individual protein
| molecules to multicellular behaviour.
|
| This seems to be a comprehensive model on a level that has never
| been seen before, so in that sense, I'm very excited about it. I
| just hope it doesn't take decades to trickle down into providers'
| hands who can actually do something to help patients.
| ramraj07 wrote:
| Immunology in general is a weird field - we simultaneously know
| a metric ton but also not much. It's like kind of we know why
| we don't know. I remember in one of the final viva exams of a
| fairly decent immunology grad student one of the committee
| members started asking, "what does IL-1 do? IL-2?..." until the
| student broke (this particular one did not, she had an answer
| for every major IL in the lower single digits). But how many
| interlukins can you even remember? There's no rhyme or Rythm
| there, no med student mnemonics to get you through memorizing
| their function.
|
| Our system is complicated by how many components play
| interconnected roles all the time it's just impossible to form
| a mental model of it.
| TaupeRanger wrote:
| It's much like neuroscience. We can say a lot about what
| individual cells and molecules do and how they interact with
| other cells and molecules. And yet, when it comes to actually
| modifying or changing anything, we're mostly hopelessly lost
| and nearly all of our solutions are of the variety: "put this
| drug into the bloodstream and see what happens, oops, that
| didn't work and took 5 years to complete trials, time to try
| the next one". The complexity is immense in biology and
| medicine and we have a hard time dealing with any of it in a
| meaningful way, other than to present extremely vague
| theories without practical use (like talking about
| "prediction" and "Markov blankets" in neuroscience, the
| "discontinuity" theory of immunity, etc.
| daoist_shaman wrote:
| I'm sure the framework they've developed applies to more
| intracellular systems than immunity. This could be an exciting
| new language to map and define many different microbiological
| processes.
| laserbeam wrote:
| > I don't know enough about biology and chemistry to understand
| much of this.
|
| The Machinery of Life by David Goodsell is a gorgeous
| introductory book on the topic. I recommend it not because it's
| the most comprehensive, but rather because it has amazing
| illustrations and it's written for a general audience with the
| purpose to be inspiring.
| WebbWeaver wrote:
| I am really, really excited for the day we are able to augment or
| manipulate the immune system in a large and meaningful way.
|
| For anyone who likes to visualize the whole kit and kaboodle of
| current human knowledge check out the virtual metabolic human
| database. They display an updated map on human metabolism
|
| Recon human metabolism map https://www.vmh.life/#reconmap2
|
| Paper overview of vmh
| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6323901/
|
| API Root of vmh https://www.vmh.life/_api
|
| and obviously https://www.ebi.ac.uk/biomodels/ is pretty good too
|
| human protein atlas
| https://www.proteinatlas.org/humanproteome/metabolic
| aaaaaaaaaaab wrote:
| Jesus, what a mess... No wonder we have all sorts of allergies
| and imnune issues.
| svachalek wrote:
| It's super complicated, but it's like alien legacy code from
| the far future. We can nitpick the obvious flaws but we are
| probably also completely underestimating some of the problems
| it had to solve. A typical person's immune system can often
| crack diseases in a few days that all the world's laboratories
| have spent decades on.
| chasil wrote:
| Allergies are likely a byproduct of the immune reaction to
| parasites.
|
| They begin with mast cells that attach antibodies to their
| exteriors, and when one attaches to something it recognizes,
| the mast cell releases histamine and other signals to begin
| inflammation. This can be enough to clear parasites that have
| not evolved to address these effects.
|
| These parasites are now rare in the developed world, and the
| mast cell would likely be better disabled. I read several years
| ago that work was being done on a method to remove the mast
| cells' antibodies, which would stop much of an allergic
| reaction.
| aaaaaaaaaaab wrote:
| Yeah, I know this hypothesis. I have a bunch of allergic
| issues (atopic eczema, hay fever), and I've been
| contemplating some kind of helminth therapy, but I'm too much
| of a coward to actually do it...
| Animats wrote:
| This sounds like a major advance. Are there commentaries on it
| from people who understand the implications? Is it useful for
| rational vaccine design, for example?
| w10-1 wrote:
| > Is it useful for rational vaccine design
|
| Not really. Vaccines -> antibodies produced from some of the
| cells modeled.
|
| This might help with adjuvants to vaccines (which are co-
| administered with vaccines to increase effectiveness by ramping
| up the immune system).
|
| Vaccine design now is pretty "rational" (well-understood): Find
| an immunogenic stable and accessible epitope on the pathogen,
| and replicate that in the vaccine. It's the *production* of
| vaccines that's hard.
|
| COVID vaccine design was tricky because the key/unique epitope
| is hidden by a conformational change until cell entry, but
| still that was basically solved in a year. The magic lies in
| the new mechanism for producing the immunogenic epitope: by
| supplying RNA templates to your own cells to produce the
| protein.
|
| The hard design/modeling problem is auto-immunity, in all its
| forms.
| w10-1 wrote:
| This is amazing work, and could be an essential methodology for
| some time.
|
| But I'd love to hear how they decided to call it a "physical
| wiring diagram"; that must have been quite the discussion.
| manholio wrote:
| In terms of information security, as viewed by an infosec
| engineer, biological systems seem to have incredibly weak
| architecture. Hear me out, please.
|
| If any piece of DNA code manages to find its way into the
| nucleus, it's happily added to the cell "runtime" and has root
| access to the system.
|
| To defend against this, biology relies on multiple layers of
| security, both physical, like the skin, and chemical, like the
| secret protein password it requires to allow foreign DNA to
| breach the cell membrane. But both are easily circumvented, for
| example weak points exist in the physical layer and the protein
| passwords are static and low entropy, easy to bruteforce by an
| enemy that already has a botnet of infected hosts which produce
| random permutations of these keys.
|
| And once infection happens, the body response is sort of like the
| experience of cleaning a Windows 98 which has been used by your
| grandma to surf the internet for the last two decades, without
| the option to do a fresh install (kill the host). It's messy and
| insanely complex - the sort of thing you would expect blind
| evolution to generate against a blind, brute-forcing script
| kiddie.
|
| You just have to wonder what are our chances on this planet if
| intelligent and rational enemies, be they human or AI, gain the
| knowledge, tools and motivation to attack biological systems and
| intelligently design sophisticated attack vectors. Our most
| precious systems are wide open, folks.
|
| Perhaps some day, to prevent such attacks, we will take control
| of this complex immune machinery and inject ourselves with highly
| engineered "anti-viruses" built on the same info-sec principles
| we build software on.
| tgv wrote:
| But that's where the "virus" metaphor comes from...
| lamontcg wrote:
| > Hear me out, please.
|
| Nope. And I hate that phrase, it rarely pans out with anything
| that makes any sense.
|
| Yeah it would be great if Nabs were all we needed and they were
| all sterilizing and permanent so any foreign pathogen was
| instantly destroyed.
|
| But the immune system has a complicated friend-or-foe problem
| which pathogens are constantly trying to exploit.
|
| I've had virus-triggered pericarditis before where presumably
| igG Nabs to the cold virus I had managed to attack my
| pericardium. Having T-cells and B-cells be latent and ready to
| activate on infection and not constantly attacking surface
| proteins is a good thing. Waning Nabs is a feature, not a bug.
|
| And the multilayered approach to the immune system probably
| means that immune escape of viruses is shuttled down the route
| where viruses focus on Nabs, while the multiple kinds of TLA
| subtypes and the secondary defense of the humoral immune system
| mean that T-cell epitopes are not the focus of viral evolution
| and immune escape.
|
| The immune system evolved the way it did based on a 500M year
| long arms race between eucaryotes and pathogens, it is really
| quite good at what it does.
|
| Of course there's weaknesses in it, but we have the advantage
| of looking at the specific virus or pathogen that we're
| concerned with and spending great effort to custom design
| treatments, while the body needs to individually react to any
| possible pathogen that the body might encounter on its own. We
| can do custom bespoke treatment having analyzed the pathogen
| extensively to start with, while the immune system's battle
| starts the moment there's first contact by the individual
| organism with the enemy. It works great for solving that latter
| problem.
|
| Most pathogens also never gain access to the nucleus and can't
| be transcribed into the nucleus.
|
| And even there, the reason why we have a placenta and are
| mammals is likely because some organism was infected by a
| retrovirus and learned to form syncytia and learned a knew
| trick from a virus. Evolution can take a seeming "fault" like
| that and turn it into a strength on the long-term.
|
| Most likely all we need to do is be able to sit down with any
| particular individual human's immune system and convince it to
| attack something even though the immune system has concerns
| about friendly-fire issues. Although the problem of doing
| something like clearing EBV out of the neurons of someone who
| is at risk of developing MS is problematic since you don't want
| to kill a lot of EBV-infected neurons (which is probably a
| "fault" of the nerve system rather than being a fault of the
| immune system -- but one again it is likely a necessary "fault"
| given the fact that we don't want to be scattershot blowing
| away nerves). That is likely to look more like CRISPR treatment
| to gene-edit the virus out of the DNA of those neurons. The DNA
| viruses that incorporate into neurons of T lymphocytes, B
| lymphocytes and neurons are indeed problematic, but that is a
| very small number of pathogens that manage to get past all
| those defenses that we have, there's a heavy amount of
| survivorship/selection bias there. The hundreds of cold viruses
| out there we clobber pretty routinely. For most everything else
| the ability to regenerate cells with the ability to kill
| infected cells works fine. The cells which "learn" stuff is
| where things get really tricky. That is almost like a UEFI
| rootkit. And our ability to prevent computer viruses is also
| primitive, we have some general heuristics to quarantine virus-
| looking code but it has a ton of false positives and we mostly
| rely on distribution of signatures of the virus once
| researchers have analyzed infected computers. The human immune
| system can protect against viruses that the human race has
| never encountered before.
| artimunor wrote:
| It's a feature, not a bug. As tux3 describes there has to be a
| combination between easy access and dealing with threats.
|
| I would like to add to tux3's comparison that in this analogy
| the small criters are vital for cell-health, they bring
| resources. And i would also like to add that nature has a way
| of propagating the white/black-list as well which means that
| predators get "marked" hence the mutation (a bit like a
| criminal wearing a disguise?) element viruses have is so
| important for them, and the thing that makes them so dangerous.
| forgotmypw17 wrote:
| As is common in IT, only the bare minimum necessary level of
| security.
| chasil wrote:
| Actually, retroviruses have contributed ~8% of human DNA, so
| you could say that past rootkits have been incorporated into
| the current ("OS") platform. I understand the mammalian
| placenta required the added viral genetic components to evolve.
|
| These retrovirus fragments can surface as "transposons" where
| they will copy themselves up to thousands of times over the DNA
| of the cell, which can happen about once a month. There are
| also "gypsy transposons" that encapsulate these viral fragments
| in a package that can "infect" a neighboring cell.
|
| Germline cells have special mechanisms to silence transposon
| activity, otherwise reproduction would be much more
| problematic.
| aaaaaaaaaaab wrote:
| Yeah, short of a complete rewrite in Rust, I don't see how we
| could survive on the long run.
| tibbydudeza wrote:
| The issue is it was never designed - just trail and error that
| nature got something that works but is kind of fragile but good
| enough that it works for the majority of use cases.
|
| Jerry rigged.
|
| A colleague has been diagnosed with Type 1 diabetes recently
| because his immune system decided last year the beta cells
| making insulin in his pancreas is now fair game.
|
| Then the recent papers show that cells in the pancreas duct has
| the ability to regulate T cell activity as if this is a known
| bug and more of us would get Type 1 than currently if it were
| not the case.
|
| As I said jerry rigged.
| Projectiboga wrote:
| My suggestions as a T1D, Melatonin upregulates the insulin
| receptor so you need less. This also helps T2D. Second there
| have been spontaneous remissions after the BCG Tuburculosis
| vaccine, it some how stops that anti-islet cell immunity.
| Bonus tip. Have them calculate half their weight in
| kilograms, that gives the number of carbs a 100mg/dl blood
| sugar equals. This helps with adjusting blood sugar up or
| down incrementally. Finally serious low blood sugar often
| start with a bleek mood or motor coordination loss. The
| shifts in consciousness are the most emotionally and
| interpersonally hard parts of this. They should not hide
| their condition and should wear a bracelet with info, one can
| become blackout drunk like in behavior. The new constant
| sensors are amazing for learning and monitoring.
| tibbydudeza wrote:
| Well it is on my mind since he collapsed last week due to
| hyperglycemia, the new monitoring (CGM)/insulin pumps are
| amazing but you need a decent medical scheme and co-pay a
| large part of it.
| tux3 wrote:
| I think you underestimate how good the immune system is! And
| where the best cost/benefit security tradeoffs are, because
| security is always a tradeoff. (The most secure system is a
| dead system)
|
| The body is constantly exposed to pathogens, all the time, in
| everything you eat, the air you breathe, everywhere. It is as
| if your laptop was downloading millions of random executables
| from every site you visit and hapilly running them (the analogy
| with Javascript and browser exploits just writes itself!)
|
| Antibodies are in the metaphor both an allowlist AND a
| blacklist. Anything that isn't a well-known protein made by the
| body (allowed) is fair game for antibodies to bind to. You make
| quintillions of these that will bind to anything under the sun.
| Once they find a pathogen, it goes on the blacklist and more
| specific antibodies are made for it, that's adaptive immunity.
| There are many further layers and defenses on top of that, of
| course, but compared to infosec this is already much stricter
| filtering than a typical endpoint protection product.
|
| It's easy to look at it and say hey we should lock down the
| cell membrane by adding randomly generated passwords and
| rotating them, that will improve security! But that's not
| realistic, a lot of simple things need to go through the cell
| membrane all the time.
|
| That would be like requiring all living beings to show a
| passport before entering your country. Your intent is that you
| mostly care about catching criminals, but the border is mostly
| crossed by birds and small critters. The cell is the same, lots
| of things go in and out all the time, and they're too simple to
| carry any sort of identification. That's like requiring birds
| to have a passport.
| manholio wrote:
| > But that's not realistic, a lot of simple things need to go
| through the cell membrane all the time.
|
| But surely something that contains an executable payload
| (DNA/RNA) needs to be better scrutinized than a simple
| nutrient. Runtime alterations of the cell code are
| practically never required, the fact that any code that
| enters the cell is fair game to execute and even to
| permanently alter the nucleus "binary"(retroviruses) strikes
| as a bad practice. A static host-key, unique per individual,
| would stop all such viruses.
|
| So you cannot shake the impression that evolution does not
| really care about the information security of any given host.
| What it cares about is overall success of the gene while
| allowing for sufficient variation and flexibility - the
| retroviruses are just a tool among many to induce such
| genetic variability.
|
| Nothing I say above should be taken as dismissing an
| exceptionally intricate and developed system, just pointing
| out the different way a rational attacker would approach the
| problem and that the defenses against such an attack would be
| fundamentally different than what evolution had to deal with
| in the past.
| tux3 wrote:
| I wouldn't really say that it doesn't care about
| information security.
|
| The DNA is actually pretty well protected, tightly wound
| inside the nucleus, which has pretty strong access control
| checks on what can enter and what can leave. It's always
| possible to break those protections, but a lot of effort
| went into "sandboxing" the rest of the cell and the
| nucleus.
|
| There are also strong checks on code circulating where it
| isn't supposed to be. If you let RNA or DNA run around in
| plain sight in the blood, your immune system will react
| immediately with extreme prejudice and excessive violence.
|
| But of course viruses and vaccines wrap that code in a
| protective layer (much like malware wraps itself with
| packers, obfuscation, and sophisticated delivery methods
| before reaching the target).
|
| And then like you said, that protective vesicle needs some
| sort of static key to enter cells, it needs to target an
| appropriate receptor to gain entry.
|
| Where things get complicated is that, while it would be
| really good to have per-host random keys, instead of a
| fixed set of receptors than anyone can trigger by 'putting
| a square shape in the square hole', the lock and key system
| of proteins is not one where you can generate a random
| receptor and the key that matches it from a seed, like you
| could in cryptography.
|
| It takes huge effort and long optimization times to find a
| protein that matches a random receptor pretty well. The
| consequence is that it's non-trivial for viruses to jump
| between animals that have slightly different receptors, or
| to find a new target in a particular host. It takes a lot
| of optimization time to find even just a single static key
| that matches.
|
| But the corollary is that it's nigh impossible for a human
| body to add a random per-host mutation to every receptor
| and everything that binds to it. It's a good idea in
| infosec, but because of the way proteins and chemistry work
| in biology, we don't have any mechanism to create the sort
| of defenses you care about.
|
| Evolution does care very much about retroviruses, and in
| fact the defenses it put in place are able to brutally
| murder the overwhelming, oppressive majority of them. I
| think the impression that it's missing some obvious
| defences is due to the fact that the kind of defense that
| works really well in biology is very different from the
| kind that works well in infosec.
|
| There are cases where evolution goes wrong, because it
| optimizes for the replication of the genes instead of the
| wellbeing of the host, that's true. But in the case of
| retroviruses, the host almost always loses fitness after an
| infection, so defending the genetic code against viruses
| tends to be strongly aligned with what evolution "cares
| about" (insofar as it "cares" about anything)
| kleer001 wrote:
| that's f-n gorgeous, I have only a slight idea what it means, but
| it's beautiful, so much work
| andreareina wrote:
| Would be a good addition to http://biochemical-
| pathways.com/#/map/1
| gzer0 wrote:
| Amazing resource. Totally forgot about the existence of this;
| definitely helped during medical school. Thanks for the share
| :)
| gzer0 wrote:
| https://static-content.springer.com/esm/art%3A10.1038%2Fs415...
|
| Link to the technical overview and mathematic modeling that has
| massive implications for the field of immunology as a direct
| result of this research.
|
| > _If cell-to-cell adhesion is mostly determined by the binding
| of complementary receptors on the surfaces of those cells, and a
| relatively complete listing of these receptors has now been
| measured, then it should be possible to predict which cells are
| most likely to physically interact with each other by counting up
| their number of binding receptors._
| photochemsyn wrote:
| This is kind of stunning. They appear to have discovered
| something like 30 novel (previously unknown) immune cell receptor
| interactions (Fig 1). Then they built a quantitive model, looked
| into where these interactions are localized in the body, and lots
| more beside. A truly ridiculous amount of information for a
| single paper. This seems to be the 'what's it all about'
| paragraph in the paper:
|
| > "The immune system is distinctive for being a distributed
| system. It is not fixed to a single localized organ in the body,
| but rather is made up of numerous specialized cell types that
| must adaptably organize their intercellular connections to
| respond to pathogens and other threats wherever they may appear.
| We provide a systematic and quantitative view of the cell-surface
| proteins that enable immune cells to dynamically wire their
| interactions. The receptor interactions that we report in our
| network each merit further individualized study to characterize
| their full roles in health and disease."
|
| For those interested in computational modeling (basically they
| simulate immune cells circulating freely within the body and
| interacting based on their receptor types), here's the
| supplementary description link (pdf), which is enough for a whole
| paper on its own.
|
| https://static-content.springer.com/esm/art%3A10.1038%2Fs415...
| photochemsyn wrote:
| After looking at this a bit more, here's something interesting.
| First, it's a very physical model, treating cells as 3D
| entities with 2D interactions (cell surfaces), and they use
| their measured binding constants (essentially a measure of
| protein-protein stickiness across all their proteins) as a key
| parameter, along with measures of protein expression in various
| immune system cell types. They're classified into: CD4 T cells,
| Helper CD4 T cells, Natural killer cells, CD8 T cells,
| Dendritic cells, Monocytes, Regulatory T cells, B cells. This
| is all quite complex, here's a simplified 6 min overview of
| some of their roles, note the importance of receptor-receptor
| interactions at every stage:
|
| https://www.youtube.com/watch?v=6eMh0Vpyoik
|
| For a nice visualization of immune cells attacking cancer
| cells:
|
| https://www.youtube.com/watch?v=K09xzIQ8zsg
|
| So, this is a complex dynamic network, and a key feature of
| such networks is that a change at one point in the network can
| percolate across the entire network, which can be critical to
| their normal functioning, as well a play roles in failure
| /pathology. The ability to model such casading effects could be
| game-changing in terms of developing treatments such as
| targeting cancer cells, blocking autoimmune activation, etc.
| From supplement:
|
| > "Another direct test of the predictive power of this model
| would be to experimentally block specific cell-surface protein
| interactions (such as by adding recombinant ligands that
| competitively inhibit their receptors' interactions) and gauge
| how cell-to-cell contact frequencies change. If these changes
| are predictable from our "ground-up" mass action kinetics
| model, that would demonstrate the utility of our systematic
| approach."
| dylan604 wrote:
| Thanks for those links. I'm not an oncologist, nor do I play
| one on TV, so I've only paid a cursory glance to where the
| current understanding of cancer cell behavior was. After
| watching the second video you linked, I'm now extremely
| curious about this field, and kind of wish I could go back in
| time to chose a different career path. The amount of details
| now known on how cells, proteins, etc work is totally
| fascinating to me.
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