Re: [asa] PSCF article on immune system

From: Nucacids <>
Date: Sun Dec 06 2009 - 00:45:45 EST

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.


----- 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 motherıs 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 itıs 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 Iım 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 Sun Dec 6 00:46:13 2009

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