Talk:Complement system

Overhaul of Alternative Pathway

I'm going through the complement system and comparing it to an Immunology text book (specifically, Immunology, Infection, and Infection by Pier, Lyczak, and Wetzler, copyright 2004) and the Alternative pathway could use some work, both for clarity and accuracy.

Major Points: C3 spontaneously breaks and activates because of a breakdown in a thioester bond via a condensation reaction. In short, it's mildly unstable in water. This results in C3(H20). C3(H20) is then capable of covalently binding to a membrane surface if it is near enough. Upon binding with a cellular membrane C3(H20) is capable of being bound by Factor B. Upon being bound, Factor B is then cleaved by Factor D into components Bb and Ba, Bb is the larger of the two components and stays attached to C3(H20) to form C3(H20)Bb, a C3 convertase which cleaves further C3 molecules to amplify the effect. Ba diffuses away. C3 convertase cleaves C3 molecules into C3b and C3a, of which C3b is the larger of the two and can bind to C3(H20)Bb to form C3(H20)Bb3b, which has C5 convertase activity.

Protection/Dissociation of C3(H20): Since C3(H20) formation is spontaneous, there is a greater chance of it causing a Membrane Attack Complex (MAC for short) to form on a host cell. This is prevented by several ways. First, Factor H in the blood causes the dissociation of C3(H20)Bb. Second, C3(H20)Bb is inherently unstable and eventually will dissociate on its own. Furthermore, mammalian cell membranes have both sialic acid and heparin, which promote binding of factor H. Factor H, in addition to destabilizing the C3(H20)Bb molecule, acts as a cofactor to allow Factor I to cleave C3(H20)Bb and inactivate it. In addition to this, mammalian cells also have structurally homologous proteins to Factor H embedded in their membranes, which have the same effect.

Stabilization of C3(H20): C3(H20) can be stabilized by the protein properdin, which is present in the blood stream.

That's enough on the alternative pathway for now, I'll also work on a more detailed diagram of the 3 pathways and how they intertwine. Let me know if I should go ahead and work these changes into the page. ~Richard, e-mail Kinnin@gmail.com —Preceding unsigned comment added by 157.62.190.17 (talk) 21:39, 22 October 2007 (UTC)

Work Needed

I agree the page needs work on the complement cascade. I compared what's here to a couple textbooks and found mistakes galore. I wouldn't trust it until someone does some serious work. As far as I can tell, the classical C3 convertase is NOT C3b2a, but rather, C3b2b. I changed the mistakes I found, but there may be more, But I'm just a medical student.134.84.152.128 (talk) 03:51, 21 January 2009 (UTC)

Spelling

Typo in "This binding leads to *cnformational* changes in C1q molecule..."

I assume it should read conformational but I'm savvy enough on this matter to be sure... someone else please correct it and delete this.--nunocordeiro

Be bold! JFW | T@lk 22:20, 19 January 2006 (UTC)

But don't be reckless Your right though... I'll be a little bolder in the future. :) --nunocordeiro 03:14, 28 March 2006 (UTC)

Categories

There is need for this article to be both in Category:Complement system and its parent Category:Immune system - parent/grandparent conflict (P/G-C). So i removed the grandparent link. I also added Category:Complement system to Category:Acute phase proteins b/c it doesn't make sence to have the article "Complement system" in the "Acute phase proteins" tree structure and not have Category:Complement system, as a result of that change i had to remove the direct link from here to "Acute phase proteins" b/c of another P/G-C. -- Boris 17:12, 9 February 2006 (UTC)

Complement system diagram

I came across the diagram I have inserted into the article while looking for diagrams for the Immune system. I added the detailed information to the diagram, hopefully it suits your needs. If more info is needed I can add it, relatively easily, to the existing diagram, let me know.--DO11.10 21:19, 5 September 2006 (UTC)

Where is Factor D on the Alternative Pathway diagram? I think the diagrams really need replacing by an english version, though these are quite clear, to their credit. Philbradley 11:31, 12 May 2007 (UTC)

Figures at the additional image section have description in Polish. Would someone who understand it be alble to translate into English? Following are the description where words with (ok) marks were perceived. There are (1) to (5) words need to be translated.

[Droga_klasyczna.png]
(ok)Przeciwcialo = antibody
(1) rozpoznawane epitopy blonowe
(2) lizowana blona

[Complemento_C3_convertasi_via_classica.gif]
(3) Il C1
(4) si lega agli anticarpi adesi antigeni di superficie di un micropganismo
(ok)microganismo = microorganism
(5) Il C1 attivato scinde il C4
(ok)C3 convertasi = C3 convertase
--Tossh eng (talk) 14:14, 19 August 2008 (UTC)

Three groups of words are added to the above comment:
[Formowanie MAC.svg]
(6) Kompleks konwertazy C5
(7) woda lizozym antybiotyki
(8) potas ATP aminokwasy
--Tossh eng (talk) 23:26, 19 August 2008 (UTC)

Other organisms?

I can't work out from reading the article if the complement system is only found in mammals such as humans, or if it is present in other organisms. TimVickers 23:32, 30 December 2006 (UTC)

Complement definatly exists in organisms outside of Chordates like Echinoderms, Arthropods, Urochordates, and possibly Annilids. Maybe someone more knowledgable in this could add a small section on non-mammalian complement? This should at least be mentioned somewhere in the page. JosephJP (talk) 19:21, 15 March 2008 (UTC)

The Caption on the MAC Complex

Caption currently reads, "A complement protein attacking an invader", which is incorrect - it is a Membrane attack complex, causing cell lysis. It is made of several different complement protein and you cannot tell if it is a host cell or a foreign cell. —Preceding unsigned comment added by 82.16.95.94 (talk) 21:47, 3 December 2007 (UTC)

differnt names in "Classical" and "alternative"

In the paragraph about the classical pathway, it is explained that the C3 convertase complex should now correctly be called C4b2b. But in the paragraph "Alternative pathway", it still says that C4b and C2a combine to make C3 convertase. I think this should be changed to "C4b and C2b etc. ..." 85.127.84.16 (talk) 14:04, 7 February 2008 (UTC)

You're right that it's confusing and that if all complement proteins followed the regular nomenclature, then the fragment in question would be C2b; however, the scientific community seems to be just as confused about it as we are. The newest version of the Janeway textbook (7th edition) reverts to calling it C2a even after explaining that the nomenclature would call it C2b. I don't have my old text, but I'm fairly certain the 6th edition did call it C2b, so it's a confused protein fragment. I'm in favor of calling it C2b, but that does put Wikipedia at odds with what's widely considered the premier immunology text. JosephJP (talk) 19:15, 15 March 2008 (UTC)

Due to the comments in some textbooks of immunology that only 'old' texts assigned C2a to be a larger fragment, C2a was changed to C2b. The comments found in the textbooks were put into the box. Was it right? --Tossh eng (talk) 09:03, 23 August 2008 (UTC)

Should mention tests, including "total hemolytic complement" (CH50)

I think that this article should at least mention lab tests commonly used to measure parameters of this system, for example the total hemolytic complement (CH50). Thomas.Hedden =============== For god’s sake, why put an image in an important article like this one in French? English is the universal scientific language – deal with it, and stop wasting people’s time. ======================

On both counts, the best approach may be for you to be bold and fix it! --Scray (talk) 11:07, 13 October 2008 (UTC)

C2a, C2b, large or small?

This controversy has been swirling for years. User Tossh eng made changes that do not resolve or capture the controversy, just tilt this page in one direction. I would have used that user's talk page, but found that page unusable - seems to be used as a sandbox. Janeway made a strong case for rational reassignment of C2b to the large fragment, so that all large fragments are labelled 'b' and small/diffusable fragments are 'a'. This would remove one of the largest obstacles to students' learning of the cascade (and acceptance of the cascade as anything but arbitrary). The major downside is the large literature that precedes this. Again, the argument is long-running. We could present both sides, as was done in earlier versions of this page. I do not agree with simply tilting to one side. --Scray (talk) 10:33, 13 October 2008 (UTC)

Editing wikipedians are two-grouped, one larger C2b side and the other larger C2a side. I myself would like to push the former side because it involves consistent denotation that any complement fragment labelled b is larger.

In the first look at the text of '22:23, 12 July 2008,' C2a was assigned to be a larger fragment. Then I changed C2a to C2b at 08:43, 23 August 2008, inserting an explanatory box about 'C2 fragment nomenclature.' However, thereafter, larger C2a side wikipedians changed back some C2b into C2a in the text, and even changed C2b to C2a, in the cited Janeway et al.'s original text adopted from their 1999 textbook in the box. They left the figure legend where the description 'C2a should read C2b' was made to be unchanged.

Meanwhile, examining textbooks by myself revealed that the balance of assignment of C2b seemed in favor of a smaller fragment, I just removed the description in the figure legend, corrected Janeway et al.'s citation, and changed the introductory part of the box saying that the majority looked in favor of a larger C2a fragment at 02:24, 13 October 2008.

And now again the text has been changed back to the former text (=the current text at 10:26, 13 October 2008). In this current text, where they seem to consider that larger C2b assignment is made, however, the assignment is mixed in the text, the figure legend, and implication of the box as in the textbook I cited in the box.

Janeway et al.'s citation in the box is wrong now but the changes have occurred 3 times: C2b -> C2a -> C2b -> C2a already, then I give up further correction.(=/-); --Tossh eng (talk) 05:25, 14 October 2008 (UTC)

Hi, it just occurred to me that the C2 nomenclature confusion is explained rather clearly here, but not even mentioned on the C2 page. Is it ok to just copy and paste the information in the table over to that page? --Anriar (talk) 16:55, 15 March 2009 (UTC)

Yes. WhatamIdoing (talk) 19:20, 16 March 2009 (UTC)

Nomenclature of Active Complement Proteins

The standard nomenclature of active complement protein requires adition of a bar over the name of the active state of the protein. For example, the protein C4b2a3b should ideally have a bar over 4b2a3b. Similarly, C1qr²s² must have a bar over r²s² as in the C1 complex these two become the active proteolytic components. I am not aware of the availability of this formatting option of putting bar over letters in Wikipedia, but if not shown the nomenclature becomes clearly wrong. Proquence (talk) 09:26, 11 December 2008 (UTC)

Some authors do not use the convention to designate activated components by a horizontal line as in a series of editions of Janeway's textbooks.

They explicitly represent their stance in the text as follows: "Activated complement components are often designated by a horizontal line, for example C2b; however, we shall not use this convention." (p. 340-341)

Another textbook is found where the authors do not put a horizontal line to indicate activated components.--Tossh_eng (talk) 02:25, 14 March 2009 (UTC)

Suggestion to merge Complement System with all the complement pathways

I would like to suggest that this article on the Complement system be merged with its subdivisions (the three pathways: classical complement pathway, alternative complement pathway, mannose-binding lectin pathway). I don't think it is necessary to have 3 short articles about each pathway when it can all be incorporated under the common theme of the complement system. Furthermore, it is unnecessary to name an article "mannose-binding lectin pathway" (too focused, wikipedia is not a dictionary); instead, these links should be re-directed to Complement system. --comcc (talk) 10:14, 27 November 2009 (UTC)