Re: [asa] PSCF article on immune system

From: wjp <wjp@swcp.com>
Date: Sun Dec 06 2009 - 09:35:48 EST

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" <nucacids@wowway.com> 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" <Craig.Story@gordon.edu>
> To: <asa@calvin.edu>
> 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 majordomo@calvin.edu with
>> "unsubscribe asa" (no quotes) as the body of the message.
>
>
>
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Received on Sun Dec 6 09:36:23 2009

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