Re: [asa] PSCF article on immune system

From: Nucacids <>
Date: Fri Dec 11 2009 - 21:06:44 EST

Hi Bill,

Unfortunately, I do not have access to Craig’s article. My guess is that
Craig is referring to the different types of antibodies (that video shows
only IgG). It’s a process known as class switch recombination. So not only
can these lymphocytes make an antibody that will strongly bind to a specific
antigen (by harnessing and controlling the power of mutation and selection),
but once they make the right antibody, they can express it in different
specialized versions (see:

And yes, antibodies largely work as markers by attracting various white
blood cells or plasma proteins to the pathogen. More than that, when they
bind to a pathogen, they can immobilize it, prevent the pathogen from
binding to other cells, or cause pathogens to clump together. If you think
of the pathogen as the prey and the white blood cells as predators, then
antibodies work on several levels to make the prey more vulnerable.


----- Original Message -----
From: "Bill Powers" <>
To: "Nucacids" <>
Cc: "Craig Story" <>; <>
Sent: Sunday, December 06, 2009 3:18 PM
Subject: Re: [asa] PSCF article on immune system


Thanks for the help and referenced material.

I do have a question regarding what I understand (albeit perhaps
incorrectly) from Craig's article.

From the Youtube video, I gather that it is really only the very tip of
the variable structure that binds to the an antigen. If this is so, why
does Craig make such a big deal about the rest of the antibody
formation, e.g. the connections of constant and variable parts?

I probably missed it in Craig's article, but it would seem that all the
important work goes on in the formation of the tip, that which makes it
specific to an antigen.

BTW, what is the importance of the binding of antibdody to antigen?
From the video, I gather that it is a kind of marker. Does this mean
that somehow it serves as a marker, that would otherwise been missed,
for leukocytes?



On Sun, 6 Dec 2009, Nucacids wrote:

> Hi Bill,
> A protein is a chain of amino acids that folds into a particular three
> dimensional conformation. A fold is a particular conformation. What
> science
> has discovered is that even though amino acid sequence variability is
> immense
> (for a protein of 100 amino acids there are 20^100 possible combinations,
> since there are 20 different amino acids), there are only about 1000 or so
> shapes/folds that are employed by life.
> You can think of a fold as a region where the amino acid chain is arranged
> into a scaffold. Function is tied to the scaffold when it is decorated
> with
> an active site (which is usually some cleft or groove on the protein’s
> surface that binds a substrate and converts it to a product), along with
> other binding sites.
> The immunoglobulin fold is a particular scaffold arrangement that is used
> to
> make antibodies (this scaffold is also found in many other proteins). So
> I
> am basically pondering whether there is something special about this
> particular scaffold when it comes to making antibodies.
> Here is a nice video that will help you visualize the immunoglobulin fold
> in
> an antibody:
> And here are a couple of essays that might help someone appreciate where I
> am
> coming from with this:
> Hope this helps,
> Mike
>> Mike:
>> You and Craig, if you are going to expect any participation from me, and
>> I
>> suspect some others, are going to have to get down on your knees, look us
>> in the eyes, and talk to us as if we are bright eyed 8 year olds.
>> IOW, I don't understand a good deal of the terminology that you are both
>> using.
>> What, for example, is the the immunoglobulin "fold" that is so prevalent
>> in
>> all creation?
>> Thanks for both your participation, and welcome Craig.
>> bill
>> On Sun, 6 Dec 2009 00:45:45 -0500, "Nucacids" <>
>> wrote:
>>> I would like to pose a question that will take people down a different,
>>> less-traveled pathway. While it is clear that mutations and selection
>>> play
>>> key roles in the generation of antibodies, is it possible that the
>>> immunoglobulin fold itself facilitates this "evolution"? In other
>> words,
>>> is
>>> there something special about the immunoglobulin fold, such that
>> mutations
>>> and selection would not be nearly as successful in generating
>>> antibody-function if another fold was used?
>>> I ask this because the immunoglobulin fold, which is universal among all
>>> domains of life, seems especially robust when it comes to tolerating
>>> mutation, yet retaining the same basic 3D shape. There are proteins
>> with
>>> immunoglobulin folds that possess 5% sequence identity and have
>> different
>>> functions. In fact, so widespread is this fold that one study that
>>> attempted to evaluate protein folds among the three domains had to
>> exclude
>>> this fold "because of the over-representation of immunoglobulin-like
>>> sequences in the NR database that made the analysis of this fold very
>>> computationally intensive." And to this day, people are still trying to
>>> figure out whether the various immunoglobulin folds are related by
>> descent
>>> or keep popping into existence by convergent evolution.
>>> Consider the possibility that not all protein folds are equally
>>> "evolvable"
>>> and that the immunoglobulin fold is rather exceptional in its
>> evolvability.
>>> Mike
>>> ----- Original Message ----- From: "Craig Story"
>>> <>
>>> To: <>
>>> Sent: Saturday, December 05, 2009 8:34 PM
>>> Subject: [asa] PSCF article on immune system
>>>> There must be a way to directly reply to a thread in this listserv, but
>> I
>>>> just subscribed, and am happy to see people discussing my article.
>>>> Let me briefly comment on two paragraphs from Bill Powers:
>>>> ³It must be something like any search program. You will have to get
>>>> "close" before a random search becomes useful. You might begin your
>>>> search "randomly", but there must be some sort of guiding mechanism
>> that
>>>> quickly narrows or directs the search, e.g, gradient search.
>>>> I suspect, from what Craig says, that the search is guided by a
>> "memory"
>>>> of previously generated antibodies, which may be why mother's milk is
>> so
>>>> important for the survival of children, or colostrum for the survival
>> of
>>>> baby goats, cows, etc.²
>>>> One must keep in mind that the variety of specificities is continually
>>>> generated whether or not there is an actual pathogen present. Then
>>>> selection
>>>> occurs as necessary. Some optimization (affinity maturation) occurs
>> after
>>>> ³hits² are found that bind the antigen reasonably well.
>>>> Second, the memory of past useful antibodies (such as the ones that
>>>> might
>>>> be
>>>> partially protecting some of us from H1N1 flu right now) are stored as
>>>> cells
>>>> that remain alive for many years. As for mother¹s milk, etc, it is the
>>>> fact
>>>> that the baby is in the same environment as the mother, and exposed to
>>>> the
>>>> same pathogens, that her useful IgA/IgM antibodies go into her milk. In
>>>> the
>>>> case of cows and rodents, actually it¹s IgG that is in the
>>>> colostrum/milk,
>>>> respectively (the topic of my PhD thesis). For humans, milk has IgM
>>>> mostly,
>>>> but the principle is the same. This transferred antibody is considered
>>>> _passive_ immunity, since it is only protein, and has a half-life, etc.
>>>> It
>>>> takes some time after birth for the newborn to be able to generate its
>>>> own
>>>> cellular responses. In your comment it sounded a bit like you were
>>>> suggesting that the transferred antibodies are somehow guiding the
>> future
>>>> cellular responders. That may be true to the extent that immune
>> networks*
>>>> are happening, but in my opinion, that is probably not be the major
>>>> factor
>>>> in immune repertoire development. I think of transferred Ab as just a
>>>> passive, temporary solution to pathogens in the immediate environment
>>>> only,
>>>> not something that ³guides² the immune system. -CS
>>>> * ³Immune networks² means something like the following: An
>> anti-antibody
>>>> is
>>>> made that has same 3D shape as antigen, then an anti-anti-antibody is
>>>> made
>>>> that again can react against the original antigen. This is so-called
>>>> idiotypic network theory. Not something I¹m really eager to get into.
>>>> Cool
>>>> idea though. The problem is to get an immune response you need all that
>>>> ³damage² signal and probably that spells trouble for the idiotypic
>>>> network,
>>>> although never write something off completely in science, especially
>>>> immunology, it might appear later.
>>>> To unsubscribe, send a message to with
>>>> "unsubscribe asa" (no quotes) as the body of the message.
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Received on Fri, 11 Dec 2009 21:06:44 -0500

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