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The Immune System is Really Amazing (and Designed)


I often get questions about the immune system, because many in the Darwin lobby point to it as an example of “random mutations”. That is kind of a half-truth, but the full truth is so amazing that it needs to be told more often.

Anyway, I’m posting this so I have something to refer people back to in the future.

The immune system is often used by the Darwin lobby to say that random mutations can have great effect. An example of this is here (see Part 2 on “Antibody Genes”) and it was used in Dover (see here). It also appears in several books as well.

There are two important processes that are often discussed. They are both important, and both involve randomness, are both highly designed, and are both well worth knowing. They are:

  • V(D)J recombination – the process that generates the initial set of antibodies
  • Somatic Hypermutation (SMH) – the process that produces new antibodies in response to a new antigen

We’ll start by considering V(D)J Recombination.

V(D)J Recombination

There a millions of different antibodies that you have to assist you. There are essentially two parts to an antibody – the CDR region (the “complementary-determining region”, which sticks to the antigen), and the C (Constant) region (which signals the immune system that it needs to come and take a look). We only have a few different C regions, each for different types of immune responses. However, we need millions of different CDR regions, because there are millions of things to watch out for.

However, we don’t have millions of genes. The total number of human genes is less than 25,000. So what happens? How do we get these millions of different proteins from a handful of genes? The genes for the CDR region are broken up into three different “interchangeable parts” – a V, a D, and a J (they stand for Variable, Diversity, and Joining, but that doesn’t really matter for our discussion). Pretty much any V can be matched with any D then with any J. Each of these “pieces” is marked with a marker that allows the genetic system to cut them at the proper place for recombination, called the RSS (recombination signal sequence). Because the process is combinatorial, you can get the millions of antibody genes needed from just recombining a few hundred gene parts!

Now, each cell recombines a different set of these gene pieces. However, how is the communication handled so that each individual cell knows which combinations have already been tried so it can be sure to do a new one? Answer – they don’t. They don’t have to! In such a process, all you need is to randomize which particular pieces you are trying out, and the net effect will be almost the same as if you communicated about which ones to do, without any communication overhead!

So, it is random in the sense that there is a combinatorial process that includes a random variable, but it is in no way random because the specific pieces which can be recombined are specifically marked, they are recombined in the proper order, and with a C region attached to the end to communicate with the rest of the cell. It is kind of a lego-like building block system – interchangeable parts that are different but with matching attachment sites. It only works if all of the parts match the design (i.e., the right size, flanked by the correct RSS so the immune system knows where to cut, etc.). There is a random component, but it is carefully controlled.

That’s the V(D)J system which lands the initial set of antibodies. But what about new antibodies? That’s where the Somatic Hypermutation system comes into play.

The Somatic Hypermutation (SMH) System

The SMH System is another wonderful system that generates new antibodies when needed. If you have an unknown antigen come into your body that your body doesn’t have a matching antibody for, then it knows it has to generate one. How does it do this?

  1. It detects that it needs to generate a new antibody.
  2. It takes an existing, antibody gene (one that is already recombined as above) that almost matches the antigen.
  3. It mutates JUST THAT GENE. Not only that, it only mutates the CDR of the gene. That is, it skips the C region (why? because it still needs to signal to the immune system that it found something! If it mutated the CDR, the communication would break down.).
  4. When it detects that it has a match, it stops mutating.

So, where is the randomness? Well, within the CDR, as best as we can figure, the immune system generates random changes. Is that really a random mutation, though? It has excluded 99.99993% of the genome and focused on the 0.00007% that it knows needs changing. What I tell people is that I will be happy to agree with them that this process is 0.00007% random if they will agree with me that it is 99.99993% designed. That usually ends the conversation.

What’s also interesting is that the cell itself starts and stops the process as needed. That is, these aren’t just happenstance mutations – the cell actively knows it needs mutations, and activates a system to produce them, then produces them within the span of 2,000 base pairs that it knows is likely to produce benefit, and then stops once it finds a benefit (it’s actually closer to 500 base pairs that get significant mutations, but there are a few rare mutations farther into the gene).

Whence Randomness

So, that is the long story of how, yes, there is randomness involved in these processes, but that is not the same thing as a philosophically random (i.e., unconstrained by systems) process. These are very constrained and directed by their systems, but they do allow small amounts of randomization precisely at the points where it is most useful to do so.

I once did a paper discussing the difference between philosophical and statistical randomness and its importance in this discussion, which you can find here.

Here’s a summary of the random-vs-nonrandom pieces of the processes:

System Nonrandom Elements Random Elements How Randomness is Harnessed
V(D)J Recombination
  • The structure of an antibody (VDJ + C)
  • The pieces that get fit together (all of the V, D, J, and C gene parts)
  • The recombination signal sequences that tell where to cut the gene.
  • The genes that do the cutting (RAG1 and RAG2)
  • The development phase when recombination happens
  • The cell types that do the recombination
  • Which piece combines with what other piece on a specific recombination.
The randomness is used to prevent communication overhead for having a massively parallel antibody generation process.
Somatic Hypermutation (SMH)
  • When the process occurs (when the organism has a selective need)
  • Which gene to modify (the antibody gene)
  • Which part of the gene to modify (the CDR region, not the C region)
  • When to stop mutating because a match is found
  • Which particular base pairs within the restricted region to mutate are randomized.
The randomness matches the amount of ambiguity that the cell can know about which locations to mutate. This makes use of Bernoulli’s Principle of Insufficient Reason to develop an effective mutation strategy.

With this table, I have probably left out an inordinate number of ways in which these systems are not random. But, my main point is that they are not random in haphazard ways, but in very specific ways that are nuanced to the needs and patterns of the process at hand.

In other words, there may be some ways that, statistically, there are some properties of randomness which show up, but there is no evidence whatsoever that this statistical randomness implies a philosophical randomness (i.e., that these mutations occur outside of the control systems of the cell). Quite the opposite – the features of these processes which are statistically random are just as tuned as the features which are not, and none of them give any evidence that you could get similar results if you had a mutation process that was not under similar types of control structures.

From the article linked to at 16 by KF: "Intelligent design (ID) is the view that it is possible to infer from empirical evidence that "certain features of the universe and of living things are best explained by an intelligent cause, not an undirected process such as natural selection" [1] Intelligent design cannot be inferred from complexity alone, since complex patterns often happen by chance. ID focuses on just those sorts of complex patterns that in human experience are produced by a mind that conceives and executes a plan. According to adherents, intelligent design can be detected in the natural laws and structure of the cosmos; it also can be detected in at least some features of living things. ... " DonJohnsonDD682
KF @ 16: Thanks for the link. Truth Will Set You Free
RVB8, you just underscored the point. You really do need to read the resources, or even just go to the NWE article on Id (which shows up wiki's hatchet job: http://www.newworldencyclopedia.org/entry/Intelligent_design ) KF kairosfocus
Many ‘lower’ plants and animals have genomes vastly bigger than our own. By ID logic these organisims have more, ‘information’.
Umm early computer's had more parts than our contemporary units. But they in no way contain more information. It is more than just a mere counting of the bits. It also has to do with what is produced. With humans and higher organisms there could be more alternative splicing and overlapping genes. This requires more information to unpack those two scenarios. And in the end your position cannot account for the information to build an organism. So you lose regardless. And we all see that upsets you ET
Kairos @11, "strawman charicatures"? Really? ID is about 'inforamtion', you can't go half a sentence in an ID blog before someone is rambling on about 'inforamtion', and 'complexity', as if the words alone prove the point. The genome of humanity has 46 chromosomes; that is the limit of the 'information' we have. Many 'lower' plants and animals have genomes vastly bigger than our own. By ID logic these organisims have more, 'information'. At what point kairos, is this observation a strawman. Please explain, using ID as your foundation, why lower stupider, less complex animals, and plants, have more, 'information', than humans. This is no strawman as it concerns, Intelligence of the Designer, Junk DNA, and the fundamental idiocy of ID. rvb8
And rvb8, if you don't like the design inference you have all of the power to refute it. All you have to do is demonstrate that blind and mindless processes can produce what we say required an intelligent designer. Do that and Occam's razor slices off the intelligent designer requirement. But don't worry as people much smarter than you don't have a clue as to how to do so. ET
I say we use the ID approach for all future scientific investigations.
You are totally ignorant of ten ID approach. Heck you are totally ignorant of evolutionism's approach.
Why did the brilliant designer give many lower animals, fungi, and plants more ‘information’, than he gave us?
See- that is your ignorance talking, again. The issue is why do you think that your ignorance means something to the rest of us? ET
RVB8 @ 6: Kindly, scroll up to the resources tab and read there to see what actual approaches are used in the design inference and linked thought. Your constant resort to self-serving strawman caricatures of the design inference on tested, reliable, observable empirical signs is long past sell-by date. KF kairosfocus
Random for a purpose? "Random numbers are useful for a variety of purposes, such as generating data encryption keys, simulating and modeling complex phenomena and for selecting random samples from larger data sets." https://www.random.org/randomness/ Dionisio
rv, #6. Think about the device that is used to control a horse. It is called a 'rein'. Now go back, look at your comment, and see if there mightn't be a point that you want to change. Hint; it's related to commonly used expressions, and what they mean. It WILL require a little thought, but you don't need to allow famous scientists to do ALL your thinking for you. soundburger
The article Belfast, "However we don't have millions of genes." Correct we have a limited number, 25,000 or so. Therefore, we should atempt to borrow more, 'information', from organisms such as many amoeba, some fungi, lots of amphibians, and various assorted other living things that have far more genes, or, 'information', than we. Why is that? Why did the brilliant designer give many lower animals, fungi, and plants more 'information', than he gave us? And thence to the credulous title, 'Wow, The Gosh Darned Immune System is Way Cooler than a Rocket, and Like a Rocket, Designed.' rvb8
@rvb8 Got it the first ten times you said it, now do you have a comment on the article itself? @PaV. I don't think you have grasped the differences in the use of the word "random" Something that is generated randomly inside a system by design is not random in the sense you are speaking of. Belfast
I say we use the ID approach for all future scientific investigations. Let's call it the, "Don't know, can't know.", approach. This approach will identify all of the irreducibly complex systems in nature, and ignore them. By this approach we will prove that the evolved curiosity of humanity should be reigned in by superstition, and faith. I'm not sure if this will advance humanity's understanding of the natural world, but it will certainly be inoffencive, to the credulous, at least. rvb8
Wow - perhaps I have mind-melded with Randall Munroe? By the way, his Thing Explainer is awesome. johnnyb
Heh! https://xkcd.com/1907/ Latemarch
There are studies done using Monte Carlo type random number generators. Does this make the results of the study 'random'? It does if you want to slam ID. PaV
Embedded Variability Framework (EVF), fully designed and implemented within the biological systems. That’s all. The rest is speculative gossiping of the worst kind. Still don’t get it? Ok, let’s try another approach. Ever heard of MSFT .NET? No? OK, read about it: https://www.microsoft.com/net/ Then you might understand what EVF is all about. Dionisio
Very interesting. Thanks. Dionisio

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