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Author
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Topic: Organisms using GAs vs. Organisms being built by GAs
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charlie d.
Member
Member # 159
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posted 15. March 2003 22:03
First of all, a word of advice to everyone: DO NOT play basketball with excited 7 year olds. They don't jump high, but run WAY too fast, and pass the ball dangerously low. ![[Big Grin]](biggrin.gif)
And now, back to our previously scheduled immunology lesson.
quote:
However, as I clearly showed in my posts in this thread, Behe correctly defined an antibody when he described them as having single specificities. As I showed, Inlay was wrong when he said that innate receptors have single specificities. For example, the scavenger receptor A recognizes ac-LDL, altered forms of bovinew serum albumin, pI:pC, and more.
I don't know Behe (I don't have DBB), but you are actually very wrong on this one. Antibodies do not necessarily have single specificities. Indeed, the vast majority of our circulating immunoglobulins (the so-called "natural" antibodies) are low affinity, broad specificity antibodies directed towards common antigens (bacterial wall moieties, for instance).
Antibodies become highly specific and gain high affinity only late during an antigen-specific immune response, through a process of mutation/selection called affinity maturation. This however has nothing to do with the VDJ recombination process we are discussing here, which takes place, irrespective of antigen, during B cell differentiation in the bone marrow.
"Naive", newly generated B cells, as they emerge from the bone marrow, carry antibodies that are mostly of low affinity. For insatnce, the antibodies produced early during an immune response (which reflect the naive repertoire) bind antigen with a Kd in the 10^-5-10^-6 M range - compared that with the high affinity, "matured" antibodies of late immune responses, which have a Kd of 10^-8-10^-9 M. Most antibodies in the primary repertoire are also not very specific – in fact, polyspecific antibodies abound (which goes along with their low affinity for antigen). As an aside, the vast majority of antibodies in the primary repertoire do not in fact recognize anything at all, and the B cells that make them die after a while without ever seeing any "action" (one of the drawbacks of the darwinian approach of the adaptive immune system – high, widespread wastefulness for rare but exceptional returns).
As for innate immunity receptors, again you are mistaken. While some of them do indeed have broad spectrum, many have quite subtle specificities, for instance TLR4 binds very specifically to the lipid A moiety of the very large bacterial lipolysaccharide (LPS) molecules. Their binding constants also actually compare quite well with those of most primary response antibodies (in the 10^-6-10^-7 M range).
The fundamental difference between adaptive and innate immunity receptors is in fact neither in their affinity nor in their specificity, but in their logic. The adaptive immune system, using VDJ recombination, can generate an almost infinite variety of specificities, and thanks to clonal selection can pick any extremely rare, low affinity antibody molecule and turn it into close to a “magic bullet” (this however has again nothing to do with VDJ recombination). The innate immune system, on the other hand, can count on only a limited array of receptors, which must focus on a few abundant antigens (sometimes classes of antigens) commonly found on pathogens (often, like LPS, molecules that we ourselves do not produce); moreover, the binding of the ligand has to be good to start with, because these antigens cannot undergo mutation and selection processes. quote:
This is relevant to both Inlay's and Behe's point. A receptor that had only a single specificity is useless, since an organism is likely to encounter various foreign substances. Thats why, although some organisms can get by with only an innate immune response, they don't do so for very long, most likely you and I wouldn't get by at all.
That's actually why we have many innate immunity receptors, each recognizing different common molecules on pathogens. And of course inactivation of the innate immune system causes just as severe a phenotype as loss of adaptive immunity –indeed the adaptive immune system wouldn’t even work in the absence of innate immunity, so that point is meaningless. quote:
Behe's point is that the Rag machine, the signals, and yes, the antibodies are needed for function. Neither you nor Inlay have shown otherwise. And a vertebrate with just a few antibodies would quickly die when it gets eaten alive by the foreign substance that it had no specificity for. Telomerases and innate receptors are irrelevant. Most likely I'll find the same errors when looking at the other aspects of the immune response. But one at a time.
As we have discussed, they are in fact not needed for antigen receptor function, unless of course you redefine the antigen receptor function to include rearrangement. You yourself have correctly identified the primary function of an antigen receptor as "to recognize antigens" (and to initiate effective immune responses, I added). This is the only function that would matter to an organism (which would not give a hoot how the antigen receptor itself is assembled), and the only one that would be subject to selection. Under this valid functional definition, VDJ rearrangement is not necessary to generate functional antigen receptors. VDJ recombination is an add-on, that indeed likely provided a selective advantage for the first organisms that carried it, giving them perhaps a broader range of responses, or allowing them to respond to pathogens capable of changing their surface molecules to evade the immune response. However, it is not necessary for antigen receptor function, unless you want to give an entirely artificial definition of the function of antigen receptor that includes VDJ recombination in its description. quote:
Charlie thinks that I somehow changed my definition of IC. He didn't go into this so I'll just wait until he comes back, hopefully he will explain it then.
Again, no, I don't think you changed the definition of IC, you changed your definition of the function of antigen receptors, to make it tautologically true that they require VDJ recombination according to the standard definition of IC. That’s quite transparent, since initially you gave the correct definition, without thinking of the implications for the ICness of the system, and then chaged it when the implications became obvious.
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Nel
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posted 16. March 2003 21:22
Charlie,
You are correct in saying the first line of defense in immunity is the result of low-affinity antibodies. Particularly IgM. Nevertheless, IgM antibodies are not very versatile, they are poor toxin neutalizing antibodies, and they are not efficient in the neutralization of viruses. Notice that what happens next is that of a long lasting memory of this contact. There is a shift in class response, with IgG antibodies appearing at higher concentrations and with greater persistence, eventually you get very little IgM, or you don't see them anymore. A little later on you may get IgA and IgE, but long story short, without this next step, IgM is useless when it comes to combatting a large array of foreign substances. Thats why you need specificity.
Specificity is usually made by a region of the antibody molecule containing the CDR. That means that they only combine with antigens that have a specific structure. Weak immune systems lead to too many low affinity antibodies, sometimes they attack the wrong thing, which can lead to paralysis.
This is why a common definition of antibody is that it is of "high affinity" or specificity.
quote:
antibody (immunoglobulin):
Protein produced by B lymphocytes in response to a foreign molecule or invading organism. Often binds to the foreign molecule or cell extremely tightly, thereby inactivating it or marking it for destruction by phagocytosis, or complement-induced lysis.
http://www.jpk.com/glossary/glossary_am.htm
quote:
An immunoglobulin molecule that has a specific amino acid sequence by virtue of which it interacts only with the antigen that induced its synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it.
http://www.ndif.org/Terms/antibody.html
I can make a loooooooooooooooooong list of definitions from textbooks that have this same definition.
As for innate immunity receptors, I'm afraid you are wrong. TLR4 binds LPS and RSV-fusion protein, and a still unidentified lipid from TB, and Hsps, and more. It is hopelessly generic. Again, all this supports Behe's point.
Whether the aquired immunity would work without innate immunity is irrelevant. And yes, the reason why organisms have innate receptors that do not have single specificities is precisely because innate receptors with single specificities is useless to the immune system. You are simply repeating my point. Again, this supports Behe's point.
As Behe pointed out, antigen receptors need RAG proteins for rearrangement. And Rag proteins need the signals. Without any of these components, you don't get antibody diversity, unless you use another machine. Remove antigen receptors and you don't get antibody diversity. Remove Rag proteins you don't get antibody diversity. Remove the signals, you don't get antibody diversity. Put them all back together, you get antibody diversity. The only point about antigen receptors was that unless the signals and the rag machine was working with receptors, the point of the Rag machine and the signals is pointless, we don't have antibody diversity, you wouldn't have antibody diversity unless you used another equally complex mechanism.
Secondly, unless the system is able to make a large amount of antibodies from the start, we won't have enough antibodies to do any good. Inlay thinks that innate receptors with single specificities already do the job. But they are able to do the job because they don't have single specificities , and they are largely irrelevant to the discussion.
Note, I never changed the definition for antigen receptor. I still think that their primary function is to recognize foreign substances. There, is, however, a marked difference between antibodies and innate receptors. And I have shown that in this post and my previous one. There is no need to change the definition with respect to IC, thus far, the IC nature of the V(D)J recombinase/antigen receptor, as I have shown, does not "dissolve". You need the receptors, you need the Rag genes, you need signals. Take one of these components away, you either have to change the function or you have to invoke irrelevant non-homologous innate receptors that don't even have single specificities.
As the paper of David Baltimore et. al. stated in Molecular Evolution of the Vertebrate Immune System
quote:
immunoglobulin and TCR genes both require RAG proteins for rearrangement. On the other hand, RAG proteins require specific recombination signals to rearrange immunoglobulin and TCR genes
Proc Nat Acad Sci, 91,10769-10770
[ 16. March 2003, 23:52: Message edited by: Nelson_Alonso ]
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Nel
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posted 16. March 2003 21:57
Yersinia,
I think the need for acquired immunity comes from the fact that innate immunity is an evolution stopper. Organisms with innate immunity get by but not for long, eventually they'll get eaten by something that their receptors never saw before.
I think Behe's point here is that there is a dangerous gap between the jump from innate immunity to acquired immunity, acquired immunity is largely successful because it can generate specificity for any kind of foreign substance. Innate immunity cannot. And then there's the fact that if innate immunity consisted of receptors with single specificities, then the likelihood of a foreign substance being recognized diminishes. Even if there are some innate receptors or something like them, with single specificities, a handful of them wouldn't be enough. Which is why Behe says that a system with only a few antibodies are "not sufficient to make a difference". Bacteria would likely be able to evade, or develop resistance to those few antibodies. It has to make a lot and it has to make them fast. Which is why I start to yawn when Charlie starts talking about how Chickens do it.
Going back to the whole issue of the specificity of the receptors, when Inlay mentions innate receptors, he is strenghthening Behe's point, not weakening it, since he is pointing to generic binders, not specified binders.
As an aside, I think that with respect to transposases (Matt Inlay's second point), Charlie referenced a paper that convinced me that there is a relationship between V(D)J recombinase, and the transposase that cannot be ignored, however Dr. Peonie made some insightful statements as well:
quote:
. The combinatorial or adaptive immune response is first seen in sharks and not in lower agnathans and lower eukaryotes. Agnathans have neither spleen nor thymus although they do have presumptive gut lymphoid tissue. This is in itself interesting because Spi genes, a marker for B lymphocytes, have been detected in lampreys. Even so, these presumptive lymphocytes do not have the elements of the combinatorial immune system and their actual function is not known.
Shintani, S., J. Terzic, A. Sato, M. Saraga-Babic, C. O'HUigin, H. Tichy, and J. Klein. 2000. Do lampreys have lymphocytes? The Spi evidence. Proc Natl Acad Sci U S A. 97:7417-22.
2. At the heart of the combinatorial immune system are the RAG1 and RAG2 genes. These genes are:
A. Not related to each other.
B. Highly conserved in vertebrates
C. Responsible for the only known site specific recombination in vertebrates
D. Not present in agnathans or lower eukaryotes.
The similarity of RAG1 to bacterial transposases, the absence of introns in the RAG genes and their abrupt appearance in sharks has led to the suggestion that these jumped into the genome as a lateral gene transfer event. If so this is a remarkable story – that two different genes jumped into the germs cells of an agnathan, integrate into an Ig molecule and then generate the diversity of antibody and TcR molecules. At essentially the same time we get the MHC genes (see below) and probably the jaw and thymus to boot.
Gellert, M. 2002. V(D)J recombination: rag proteins, repair factors, and regulation. Annu Rev Biochem. 71:101-32.
Bartl, S., D. Baltimore, and I.L. Weissman. 1994. Molecular evolution of the vertebrate immune system. Proc Natl Acad Sci U S A. 91:10769-70.
Laird, D.J., A.W. De Tomaso, M.D. Cooper, and I.L. Weissman. 2000. 50 million years of chordate evolution: Seeking the origins of adaptive immunity. Proc. Natl. Acad. Sci. U.S.A. 97:6924–6926.
3. The MHC class 1 and class 2 genes that function in antigen presentation appear just as abruptly in sharks as do the RAG genes.
Klein, J., and A. Sato. 1998. Birth of the major histocompatibility complex. Scand J Immunol. 47:199-209.
4. The TcR and Ig genes make their first appearance in Sharks. With respect to finding ancestral sequences to these genes I quote directly from Laird et al., (2000) and include their citations.
“Many investigations have approached the hypothesized primordial receptor by searching for relics of Ig-type molecules in classes of organisms that diverged before agnathans. Sequences isolated from hagfish (15, 16), tunicate (17), and sponge (14, 18) aligned with canonical Ig domains produce a similarity score that falls into the ‘twilight zone’ of questionable homology’’
Laird, D.J., A.W. De Tomaso, M.D. Cooper, and I.L. Weissman. 2000. 50 million years of chordate evolution: Seeking the origins of adaptive immunity. Proc. Natl. Acad. Sci. U.S.A. 97:6924–6926.
[ 16. March 2003, 22:55: Message edited by: Nelson_Alonso ]
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yersinia
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posted 16. March 2003 22:55
quote:
I think the need for aquired immunity comes from the fact that innate immunity is an evolution stopper. Organisms with innate immunity get by but not for long, eventually they'll get eaten by something that their receptors never saw before.
Sounds like selective pressure for acquired immunity, at least for larger, longer-lived organisms. How is this anything vaguely like an "evolution stopper"??
I agree that acquired immunity is necessary for the survival of long-lived "higher" vertebrates. But you think, just maybe, that the ancestors of vertebrates had somewhat shorter lifespans (and larger brood sizes)?
quote:
I think Behe's point here is that there is a dangerous gap between the jump from innate immunity to acquired immunity, acquired immunity is largely successful because it can generate specificity for any kind of foreign substance. Innate immunity cannot.
Yeah, so acquired immunity would be an improvement, **but immunity still exists without it**.
quote:
And then there's the fact that if innate immunity consisted of receptors with single specificities, then the likelihood of a foreign substance being recognized diminishes. Which is why Behe says that a system with only a few antibodies are "not sufficient to make a difference". It has to make a lot and it has to make them fast.
I don't know what you're trying to argue here. Innate immunity has both specific and general receptors (and if I recall correctly, a significant amount of receptor diversity just encoded in the genome). Both are useful.
And furthermore, it was already pointed out to you (top of the page) that antibodies aren't necessarily all that specific either.
None of this addresses the central flaw in your and Behe's argument, which is that the function of antigen binding does not require rearranging ability.
Where's the "dangerous gap"? Organisms clearly survive just fine with just innate immunity. Rearranging is just an improvement on genome-encoded receptor diversity. It's a modification of pre-existing receptors. And there is a fair bit of published literature discussing how the rearranging system evolved, literature which Behe mostly missed and which furthermore has been expanded on greatly since 1996. It was discussed back in the middle of this thread.
Look, here is the main point of this thread (and Inlay's article) as I see it:
Behe said that there was no literature, scientists had no clue, etc., about how IC systems evolved. He was wrong, in spades, in the case of the immune system. His reasons for why the immune system couldn't have evolved were also wrong and based mostly on lack of knowledge of the evolutionary immunology literature.
If you have challenges to the above thesis, please just list them specifically. It's not at all clear what you are arguing at the moment.
[ 16. March 2003, 23:04: Message edited by: yersinia ]
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Nel
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posted 16. March 2003 23:27
Yersinia,
I addressed all your points in my previous post. Without acquired immunity you don't have larger, longer-lived organisms in the first place. The problem is that a gradual, step by step evolution of this IC system doesn't work. You have to make specified antibodies and you have to make a lot of them in order to deal with an attack by foreign substances. As I showed, it is unlikely that innate immunity has specific receptors. Nonetheless, even a few specific receptors wouldn't be "sufficient to make a difference". A receptor with a single specificity can be bypassed or adapted to by a bacteria. There is also the problem of the loss of those receptors with single specificities through stochastic evolution (I think Julie Thomas made this point a while back). Which means if a pathogen whom that specific receptor was acting as an antibody for disappears from the population for a while, a mutation occurs where loss of that specied innate receptor or group of specified innate receptors are now gone, this is inherited in a population, the pathogen comes back, they all die.
Again, the gradual evolution of broad ranging receptors to specified receptors is kind of couner-intuitive when it comes to natural selection.
Yes IgM is a low affinity antibody but thats irrelevant. The major purpose of IgM is precisely to get to the high-affinity response.
You say that the flaw in Behe's argument is that antigen-binding does not require rearranging ability. But, unfortunately, that wasn't Behe's argument. In this particular section, he was talking about antibody-diversity. It's easy to tear down a strawman, harder to respond to the right one.
Secondly, it seems, if Dr. Peonie is correct, that the immune system did not evolve, and the literature shows this. These are my challenges to the your thesis and I have shown them.
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charlie d.
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posted 17. March 2003 10:39
Nelson:
I don't have much time right now, just a question:
are you saying that the primary antibody repertoire (the one that generates the early immune response, low-affinity IgM antibodies) is not what the "core" function of antibodies is really about, and what matters is the high-affinity, high-specificity, secondary response type of antibodies?
Just need to clarify this point. Thanks.
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Argon
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posted 17. March 2003 10:55
Neslon Alonso writes:
quote:
Without acquired immunity you don't have larger, longer-lived organisms in the first place.
Should we assume that components for acquired immunity initially arose as a defense against highly mutable "invaders"? What if parts of the system were initially adapted from a system that detoxifies food or other environmental toxins by binding and sequestering hazardous substances? Added flexibility could be acquired subsequently.
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gedanken
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posted 17. March 2003 15:00
I would like to point out the new thread:
A sequence of tests for IC.
What I would like is that a sufficiently detailed definition or presentation of the test for IC be given in that thread. Then we can apply the definition or test here to understand how it applies. I think that many of these arguments continue to show confusion because of lack of clarity of definitions of IC and tests for IC. I think this is the case in this discussion. So if one has a clear definition of IC or a clearly defined test for IC that can be presented, I suggest the new thread -- then you can refer to that particular definition.
One of my primary objectives is to avoid logical fallacies that might occur because definitions of terms are changing mid-argument. If you present your best case definition of IC and tests for IC in that thread, then here you can point out which definition of IC you are referring to. For example Micah proposed several distinct categories of definitions of IC:
MP series = multiple part category
CS series = construction sequence category
CW series = Complex whole category
Surely if one is mixing references to different definition categories one cannot be making a presentation that is consistent. But with distinct definitions and tests for IC, one can refer to which definition or test is being spoken of -- and thus make a more clear and logical argument. (But then of course others can hold the presenter to account for mixing definitions and producing logical fallacies if one is not consistent in usage of terms. One can have multiple meanings of terms -- I am simply requesting that one distinguish which definition one is using, and if multiple definitions are used in a single argument that the differing cases be distinguished by different terminology. This is the purpose of the new thread, to give potential names to the different terms, so as to allow for consistent application of terminolgy.)
[ 17. March 2003, 15:01: Message edited by: gedanken ]
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Nel
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posted 17. March 2003 16:44
Charlie,
I think all the fuss about aquired immunity is it's ability to be specific. This can be seen in the simple observation of people who survived the bubonic plague. They were able to do so quite easily in subsequent contacts with the plague. Establishment of this memory for generating a specific response is, after all, the purpose of public health immunization programs.
Arg,
Because of the irreducible complexity of the V(D)J recombinase/receptor components, we need to invoke another function for the aquisition of that immune system. But as I said before, while gradual trial and error co-option events are taking place, large animals die. This is not like flagella where at least the thing doesn't necessarily have to move to survive. This is why Behe says that animals with a few antibodies are "not sufficient to make a difference." and thats where the issue of minimal complexity arises.
I think because of the irreducible complexity of aquired immunity and it's various aspects, the parsimonous view is that it is the result of lateral gene transfer. This fits nicely with a "front-loading" view of evolution. I think aquired immunity was not derived from innate immunity, it was a new invention used to solve a new problem.
[ 17. March 2003, 18:04: Message edited by: Nelson_Alonso ]
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charlie d.
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posted 17. March 2003 19:30
LOL, Nelson. Do you realize that what you are now talking about, immunological memory, is yet another property, functionally unrelated to VDJ recombination, diversity, affinity etc? You are starting to look like a whirling dervish.
Alright, let's try to put some order here. According to your most recently revised definition, the "core" function of the antigen receptor "IC" system, based on VDJ recombination of antigen receptor genes, has to display the following features:
a) it must recognize antigen and activate an immune response (original definition)
b) it must recognize antigen specifically (no polyreactivity - arbitraily set at what? 2 antigens/receptors? 3? This is unclear.)
c) it must recognize antigen above a certain threshold of affinity (arbitrarily set at some value higher than innate immune receptors, say 10^-8 M)
d) it must display diversity in antigen recognition (arbitrarily defined as diversity with a single molecular complex, thereby excluding systems in which diversity is achieved by utilizing many receptors - such as innate immunity)
e) it must display immunological memory.
Did I miss anything? Now, do all these features need to be there? For instance, you seemed to say above that primary IgM responses do not really fit the definition, because they lack at least c) and d), and thus their function is incomplete, good only to generate secondary responses. Is that right?
[ 17. March 2003, 19:55: Message edited by: charlie d. ]
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Nel
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posted 17. March 2003 20:21
Actually Charlie, what I was referring to is specificity (but memory as well). Specifically, (pun intended) the fact that the secondary (and subsequent) exposure uses the expanded number of antigen-specific lymphocytes genereted in response to the primary immune response. Thus, I am less like a whirling dervish and more like an embedded rock.
Now you say again that I revised my definition, but I am simply using you as an authority on what is IC about the V(D)J recombination/antigen receptor:
quote:
the ICness of the antigen receptor/VDJ recombinase system (you can't have one without the other), as proposed by Behe, dissolves.
I tested this assertion and found that it was false. The antigen receptor/VDJ recombinase truly does not work unless you have one with the other. And if you don't have the signals the system is functionless. And if you don't have the Rag machine the system is functionless. If you don't have the receptors the whole thing is pointless. Thus it is IC.
The argument was made that receptors without VDJ recombinase are effective, because innate receptors with single specificities are effective antibodies without the need for VDJ recombinase.
This was false. As I have shown, it is very unlikely that innate receptors have single specificities. And this error is fatal to Inlay's argument against Behe's chapter 6 (and there are more to come). Generic binders are only analogous to antibodies.
Now you are trying to salvage the argument by saying that IgM is of low-affinity and therefore akin to these innate receptors. But as I also showed, IgM alone is inneffective against an onslaught of a large array of antigenic challenge. IgM does not last very long itself.
Consider the fact that low-affinity antibodies are dangerous to the animal. A weak immune system leads to recombining non-specific antibodies rather than the normal specific antibodies. The low-affinity antibodies attack the wrong thing, say misidentifying self tissue from non-self tissue. Take silicone. A weak immune system producing non-specific antibodies mistake collagen for silicone and this leads to all sorts of tissue disorders.
[ 17. March 2003, 20:34: Message edited by: Nelson_Alonso ]
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gedanken
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posted 17. March 2003 21:30
quote:
I think all the fuss about aquired immunity is it's ability to be specific.
But is not acquired immunity somewhat non-specific, only fairly narrowly specific but not entirely specific? For example cow-pox something causes an acquired immunity that also covers smallpox. The immunity if fairly specific, but it is not entirely specific to the exact organism. As in virtually all cases of biological complexity, there are matters of degree here -- and that is the point because “degrees” give pathways for evolutionary steps to be selected as the degree of effectiveness changes in small steps.
Something that appears to be ignored here is that there are degrees of incursion of such things as “silicone” or “secondary exposure” in the environment are subject to matters of degree. The amount of silicone in the environment may be small on the periphery of an area in which the center has a lot. Thus a small degree of protection gives an evolutionary niche around the edge or area of the concentration. And exposures also occur in degrees -- for example the number of infecting organisms can be different. A single infecting organism is usually not sufficient, and any other number is a matter of N+1 compared to N, clearly matters of degree. So only partial specificity still provides a degree of better fitness in some possible cases.
Also, without repeating the insertion of a claim that a case example was an abstract “test procedure”, could we outline the generalized steps for testing for IC being used in the A sequence of tests for IC thread, and could we name which definition of IC is being referred to here? (And if multiple definitions are being referred to, could they all be listed, and if one that is not listed is being used, could we please list it on that thread?)
[ 17. March 2003, 21:37: Message edited by: gedanken ]
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charlie d.
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posted 17. March 2003 21:50
I am getting more and more confused here, Nelson. In part I am afraid it's because I can't get you to answer questions in a straight manner.
It seems you are by an large agreeing with the list of functional features I proposed at the real "core" of the antibody system (I guess we are currently ignoring the TCR system, for simplicity - that's OK because that's another immunological can of worms). To reiterate these fucntional features: antigen recognition, high affinity, single specificity (thanks for clarifying that), diversity, memory.
You also reiterate that the IgM primary response does not fulfill this functional requisites (in particular, affinity and specificity). You need them all to fulfill the adaptive immune system function.
So, now, where would in this scheme of things the following kind of immune system fit? Say, one with real antigen receptor genes, with RAGs and recombination, high recombination-generated diversity, but only able to produce polyspecific, low affinity antibodies (with little or no affinity maturation during secondary responses) and with essentially no immunological memory.
Would you predict it to be ineffective, for instance to support the life of a large vertebrate? Would you say it is still IC, but to a lesser extent that ours? (In that case, are there other IC components you'd like to add to our system, besides genes, RAGs and RSSs?) Would it be possible for such a primitive system to be an evolutionary precursor to ours?
[ 18. March 2003, 07:49: Message edited by: charlie d. ]
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Nel
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posted 18. March 2003 19:44
Ged,
It is simply false that all cases of biological complexity are a matter of degree.In fact, this is the point about bringing up IC systems. You see, with IC systems you don't have "degrees". You either have it or you don't. I went quite deeply into this when I discussed IC and non-IC systems both in your thread and in this one:
Evolving Inventions
Although, I stopped because it went way off topic and I was just repeating myself. With flagella, there is no "degree" of motility, once you remove an essential component, the degree of motility is zero. With VDJ recombinase/receptors, if you don't have antigen receptors the degree of antibody diversity is zero.
The deal with cow-pox and small pox is still an example of specificity. The antibody is specific to the epitope for cow-pox, but small-pox shares that epitope. It's called a cross-reaction. Antibodies bind only with those substances that contain one particular antigenic structure (although they might also bind, albeit weakly, to another that is slightly related).
As far as your point about niches, the problem is that the existence of a vast array of potential antigenic epitopes. So there is no "periphery", you need a large repertoire of antibody molecules, which is capable of binding with a particular antigenic structure. An organism is likely to encounter millions of challenges, without this system, you reach evolutionary dead ends as the ones I describe above.
As far as which definition of IC I'm using, take your pick. They are all equivalent in that they involve *raw* chance events, and unselectable steps. The very discussion of the ICness of flagella, ATP synthase, and relevant here, V(D)J recombinase/antigen receptors, are test cases that emphasize the unlikely Darwinian origin and the likely intelligent origin.
[ 19. March 2003, 00:16: Message edited by: Nelson_Alonso ]
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Nel
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posted 18. March 2003 20:51
Charlie,
Here is my functional definition of effective antibodies with respect to immunity:
1. The ability to be specific
2. The ability to exhibit great diversity.
3. The ability to neutralize toxins
4. immobilization of microorganisms.
5. neutralization of viral activity
5. clumping together of microogranisms.
6. binding to soluble antigen for the formation of precipitates.
7. activating complement
8. Being able to cross the placenta from the mother to the fetus.
Of course then you have the memory response, which provides an obvious selective advantage to someone who survives the initial attack (an example of natural selection used by intelligent design).
With the precursor you describe, the minimal complexity of the recombination machinery is most appreciated. With those organisms that just have innate receptors, or even one or two antibodies, are in an arms race that may be too much for them. Just as the Red Queen said, "Sometimes it takes all the running I can do to stay in the same place." At least thats Behe's point. I think thats why it's most parsimonous to say that it arrived in large vertebrates or at least was in wait for large vertebrates, as the result of a lateral gene transfer event.
I think this also an example that shows just how much intelligent Front-Loading is different from gradual Darwinian evolution, but I digress.
I hope my post cleared things up.
[ 18. March 2003, 20:53: Message edited by: Nelson_Alonso ]
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