The Complement Pathways

a.k.a. How rioting glue bottles caused incredible cellular damage.

Preposterous, I know.  But what about when your prof gives you the three complement pathways to know step by step?  Preposterous, I know.  So let me tell you a little story to help you remember how this thing works.


First of all, check out “About” to find out how to use this site.  Please always refer to your own lecture notes if there are discrepancies.  Also, keep in mind that this is meant to help you by providing a strategy you can use yourself, or by providing a story that you can modify and add to suit your studying needs.  So as I tell you this story, scribble away and add in more info from your notes!  Now pull out your notes or textbook and let’s begin:


The Classical Pathway


Once upon a time a Glue Bottle Lot #C1q bound to an antibody-antigen complex (yes that is an anti-body sign and a raccoon).  Then Glue Bottle Lot #C1r activates itself and starts picketing because the conditions inside the glue factory suck.  This causes a second glue bottle from the same lot to take up the cause.  Together, these two fussy Lot #C1r glue bottles shout for the Lot #C1s glue bottles to join them.  Of course they are successful because…because that’s how complement works.  


Now it’s great that C1s has joined forces because C1s glue bottles are sandwich builders.  So the C1s whips out a knife and cleaves some baguette and apples for sandwiches.  In this case the “a” component of C2 is larger so it is represented by the big piece of apple and the “b” component is represented by the slice of apple.  The apples (C2a) bind the baguette (C4b) and you end up with C3 convertase.  Are you paying attention?  Just checking :)


C3 convertase hydrolyzes C3 (what? No! that’s too obvious).  This means the police are getting involved.  We start with a pair of police people and then due to the power of the C1s and their sandwiches, the two police get split up.  The taller police goes and handcuffs the C3 convertase and altogether they form C5 convertase. What do you think C5 convertase cleaves?  Yeah, that’s right.  C5. Wow.


So basically we have a case where the police calls in his canine friend (C5) but the power of the the glue bottle/sandwich combo prevails and chops the leash, releasing C5b.  The canine (C5) binds to a bone (C6).  And then this canine is on a roll!  He goes and steals a shoe and books it for his doghouse.  To commemorate such an eventful day, bone (C6), doghouse (C7) and shoe (C8) charms are added to the collar of said canine (C5b).  Then those funny things (C9) you use to throw tennis balls for dogs just magically appear all around the dog.  This forms the MAC complex and there you have your MAC attack.


The Lectin Pathway


This one’s easy to remember if you know the classical pathway.  Mannose-binding lectin sounds like something sweet and sticky so it was represented here as a jar of honey.  MASP sounds a bit like WASP (in caps because wasps are SCARY) and so that just completes the sweet scene.  Besides, mannose-binding lectin associated proteases indicates an enzyme, so maybe that stings?  Anyways, once the MASP binds the MBL you basically just jump into the classical pathway at the point where the C1s is making apple sandwiches.  Guess honey wasn’t enough and the bee decided to find the apple.


The Alternative Pathway


Too bad it’s not an alternative to learning the other pathways, cause it’s a lot simpler.  So you have some police hanging around and then it starts to rain.  The little one (C3a) gets into the police car and drives away and the tall one (C3b) runs for cover under a foreign surface (can bind to antigens here).  The police is just starting to relax and wipe the rain off his face when he hears vicious barking.  


It’s Factor D!  The police thinks quickly and grabs hold of Factor B, who is not terribly impressed.  Factor D comes and (after barking menacingly at C3b) bites Factor B in half, leaving Bb.  This tips Bb to the side and C3b is in danger of falling.  All of a sudden a little girl named Properdin (yes, that’s a flower headband) comes in and grabs hold of Bb.  She demands to know where her puppy went.  The police shouts for backup.  


Another C3b gets his call and comes to his rescue.  Unfortunately, he too gets stuck to Factor B and now Factor B is quite distressed!  This combination of two C3b’s and Bb forms a C5 convertase. And guess what?  It cleaves C5, releasing the canines from all their human companions!  Then the C5b’s run amok, eating bones, chewing shoes, and hiding in doghouses, etc.  And then we have…MAC attack!  Again.


Yay!  Congratulations!  You’ve made it through the strangest story you’ve ever heard in your life…well, unless you’ve read any of my other stories!  If you want more, check out the functions of complement.  Questions?  Please talk to me on the contact page, after all this is one of my favourite topics!


Reference (yes, this story was actually based on fact):

Kindt, T., Goldsby, R., & Osborne, B. (2007). Kuby Immunology (6th ed., Chapter 7). New York: W. H. Freeman and Company.

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