Re: Seanpit's immunity lesson for today


Marc wrote:

< snip >

The next passage starts: "Each educated immune cell only has
one type of antibody..."

There is just one problem.... Sean, T-cells don't make antibodies.

B-cells cells do make antibodies. And, T-cells have specific surface
antigen receptors at are analogous to antibodies. Perhaps I should
clarify this in greater detail, but this really isn't significant to
the point at hand.

T-cells get educated in the thymus by a combination of positive
selection (of the beta chain for self-MHC) and then negative selection
(where thymic expression of various self antigens allows for the
antigen to be presented in the context of MHC) and many auto-reactive
T-cells undergo apoptosis and are thus deleted, but not all of them.
While the T-cell receptor is analogous to an antibody, it is NOT the
same thing at all. No wonder you have so misunderstood my posts.

While this passage could use clarification, T-cell receptors are
analogous to antibodies.

B-cells, which make antibodies, are not thymically educated.
All of the potential antibodies, good, useless or autoreactive, are
there available to be made. No B-cells are deleted. Amongst these
facts is the reason why hypermutation can occur in B-cells but
not in T-cells, and the presentation made about how antibodies
are constructed leaves out the whole basis of the CDR3 region as
the antigen binding site and the role of nucleotide insertion in the
random formation of the binding pocket. (I'll have to explain later
how it is not correct to speak of hypermutation as "random" in
the way Sean tries to use it. First we have to get B-cells and T-cells
to be doing the right things, and figure out what sort of antigen
Sean is talking about at what time, which he has quite mangled.)

The problem here is that B-cells though not deleted like T-cells,
require stimulation to reproduce by T-cells. T-cells run the show.
Therefore, T-cell thymic education is all that is really needed to
effectively eliminate self-antibody producing B-cells from significant
consideration.

From Sean's http://www.detectingdesign.com/immunesystem.html

************ Begin quoted material********

Now that we understand just how important it is to recognize bad
"bugs", how do our bodies become capable of recognizing the millions
and billions of things that can make us sick? Well, it is through a
Darwinian-style selection process where the fittest survive and the
weakest die. In our bodies we have cells that are specialized immune
cells. They go to "school" to learn the difference between "self" and
"non-self". Certainly one would not want their immune system to
attack their own body! Sometimes this does happen and it is referred
to as an autoimmune disease. However, normally, the immune cells
are educated in a very tough school so that they do not attack self.
But how exactly are they trained to recognize the difference between
self and non-self?

All immune cells are capable of recognizing certain molecules
(antigens) that are on the surfaces of all "self" cells in the body
that they are supposed to protect. They sense or "feel" these
molecules with their own Y-shaped molecules called antibodies
(like little hands). Those immune cells that do not recognize
self-antigens as being part of the body are killed off before they
get out of school (and this is a rather large majority of the
"students" that enter this school). It is a tough school indeed
if the students do not learn their lessons! Those cells that do
recognize self-antigens as "self" graduate to go and search the
body for non-self antigens to attack and eliminate.

Each educated immune cell only has one type of antibody so only
one specific antigen can be recognized. Since there are millions
and billions of different possible antigens, how do the immune cells
cope with such a variety of potential enemies? Well, there are
millions and even billions of immune cells produced by the body.
Most of them will recognize a different non-self antigen. Chances
are that if enough non-self enemies get into the body at least one
of the immune cells will recognize the non-self antigens located on
this invader as "foreign".

*************************** end quoted material**********

I'll have to come back later with some details about these BIG
numbers, since a working figure is that about one in perhaps
5,000 naive lymphocytes will recognise and antigen in a functional
sense. At worst, one in 50,000 cells could be considered but it
does not take millions of different antibodies - let alone billions -
to form an adequite repertoire. This error is one of scale however
while the other comments he makes show misunderstanding of
the immune system at a fundamental level.

I didn't mean to indicate that it takes billions of different
antibodies to form an adequate repertoire initially. It just takes
billions of potential antibodies to form an adequate immune system. If
the immune system could never form more than a limited range of 50,000
or so antibodies, it wouldn't be very effective. It is because it has
the potential to form any one of billions of different antibodies that
it works as well as it does.

************ Begin quoted material********

Many people, including many scientists, claim that this process
is evolution in action. Is this actually true? After all, this system
does use survival of the fittest and a function-based selection
process to create an incredible diversity of immune cells. Is this
not evolution in action? In thinking about this question, remember
that the immune system had no initial knowledge about all the evil
antigens in the world or just which ones it might have to combat.
So, how did it get its gigantic arsenal of options? Through random
mutation and function-based selection. This is evolution in action,
but it isn't quite what many evolutionists think it is. Lets look into
this process in a bit more detail.

[... here I skip three short paragraphs on antibody V-D-J segments
where Sean fails to correctly describe the CDR3 binding pocket....]

The large number of different options and their different possible
combinations give rise to the huge variety of antibody possibilities.
This number can be roughly calculated as follows: Light chains
have 250 V-segments, 4 J-segments, and 3 possible joining frames.
This gives a total of 250 x 4 x 3 or 3000 different kinds of complete
light chain possibilities. Heavy chains have 250 V-segments, 15
D-segments, 5 J-segments, and 3 different joining frames. This gives
a total of 250 x 15 x 5 x 3 or 56,250 different kinds of complete heavy
chain possibilities. Combining the chains gives around 1.7 x 108
(~170 million) different possible antibody arrangements. Adding in
the various hypervariable differences within the variable regions gives
around 1 x 1010 (~10 billion) different antibody specificities.1,2


*************************** end quoted material**********

Wow. Sean even has two (textbook) references, a biochemistry
book from 1988 and "Immunobiology" by Janeway and Travis from
2000. He also credits his mentor, Jerry Bergman. That's all he cites.

Does he cite *anybody* who calls an immune response modulation
"evolution in action" apart from in a broad sense (which Sean does
not mean), let alone any scientists? Never, because it's not at all
true.

Again, Marc, I don't care if you don't want to call immune system
modulation real "evolution". I wrote this post in response to many
evolutionists who frequent forums like this one who do indeed use
immune system modulation as a key example of evolution in action. I
just happen to agree with them that there is no fundamental difference
as far as how functional changes over time are achieved.

Explain to me the fundamental difference between immune system
modulation and functional evolution over generations in any living
thing - Dr. Buhler. B-cells do indeed experience random genetic
changes from one B-cell generation to the next that produce functional
differences in the antibodies produced that in turn provide
reproductive advantages to those cells in each generation that produce
the best matching antibodies.

If you don't want to call that "evolution", just because there aren't
"enough" generations or because there are no "gametes" involved - be my
guest.

I may go look at Charlie's book tomorrow to see how Sean was
able to copy an illustration but get the ideas completely wrong.
(I've met with Charles Janeway, Sean, but have you?)

Maybe Sean should have cited this, too:
http://microvet.arizona.edu/courses/mic419/Tutorials/antibodygenes.html
but the numbers here are a couple of orders less than Sean gives,
and actually both sets miss the point - epitopes merge into one
another as the differences become slight, and cross-reactivity
often can be seen. The practical immune repertoire is on the order
of tens of thousands of epitopes, not "trillions", "billions" or even
millions.

The original repertoire need not be billions or millions, but the
potential repertoire does need to be billions. If the potential
repertoire was limited to a few hundred thousand, the immune system
would be much less effective than it is.

Sean also says:
"So, beyond the lowest levels of functional complexity evolution
simply stalls out this side of a practical eternity of time
(i.e., trillions upon trillions upon "zillions" of years of time)."

and

"So, we see that even though the immune system does undergo
random mutation with function-based selection and survival of
the fittest with improved fitness over time, this is not a very close
parallel to Darwinian-style evolution when it comes to explaining
the evolution of many systems of function that exist within all
living things. .... Such template-matching evolution just doesn't
solve the problem for the larger Theory of Evolution."
http://www.detectingdesign.com/immunesystem.html

This whole issue of "Darwinists" and the Immune Systen is very
strange, especially when Sean tries to argue it both ways. What
is extremely troubling is how Sean messes up the whole structure
of how the immune system functions, with his claiming antibodies
are a result of thymic training.

Perhaps I should clarify this part a little further, but this really
has nothing to do with the main point of the paper. B-cell antibody
production is limited by T-cell thymic training. The end result is the
same - ideally.

Only with the broadest latitude of
allowing for writing to a lay audience and leaving unspoken the
reason or role of T-cell "help" (which allows B-cells to produce
antibody) could there even be a possible interpretation of his
description as correct (such as where he spoke of "self antigen"
at one moment when class I MHC would have been correct and
continued to speak of "antigen" when the term was NOT meaning
any MHC but the epitope presented in the context of MHC)

I am writing to a lay audience here. I'm not indenting to go into
great detail about all the subtleties of immune system function. My
basic point is very simple and straightforward and doesn't need such
detail.

and
he then says "they sense or 'feel' these molecules with little Y
shaped molecules called antibodies", when it is the T-lymphocyte
receptor for antigen (NOT antibody) that interacts with the MHC
on most other cells of the body.

Fine - I'll modify this description to note that the T-cell receptors
are like antibodies.

Other such descriptions are too
poor to allow for artistic license, plus he should try to explain
things properly to any audience.

Maybe he should have looked at this site first:
http://microvet.arizona.edu/courses/mic419/Tutorials/antibodygenes.html

Sean - even if you were writing this web page for children you should
have done a better job explaining the correct roles of T-cells, thymus
(that's what the "T" is for, dude), antigen (be it non-self, MHC, or
otherwise), B-cells and antibodies. Education is NOT training, and
B-cells do not go through the thymus. And using your twisted version
of immunity to argue about "Darwinism" is absolutely, totally bogus.
It's just plain wrong.

The main point stands. Your nitpicking here really is irrelevant to
the point that random mutations and function-based selection over
generations of B-cells are indeed involved in good immune system
function. I'm amazed that you try to argue that there just "aren't
enough generations" to call this sort of thing real function-based
evolution. Your "no gametes are involved" argument is also very
special.

I sometimes get the feeling, Sean, that you are really some sort of
"super-troll" who is getting these things so badly expressed because
you are really one of *us* trying to make *them* look bad. Are you?
Are you really a true Darwinian believer who is trying to discredit ID?
Or do you think that having Jerry Bergman as mentor is a good thing?

You're quite an exceptional foil yourself ; )

(signed) marc
M. McWilliams Buhler, Ph.D.

Sean Pitman
www.DetectingDesign.com

.

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