Flashcards in Complement Deck (32):
Which system is an immune surveillance system of plasma proteins that act in cascades to selectively kill extracellular pathogens and diseased tissue, promote inflammation, clear tissue damage and relate tissue homeostasis?
*Most components made in Liver, make up 15% of plasma globulin protein, pattern recognition system
What are the 3 pathways of the complement system?
What are the 7 categories of complement components?
5-Membrane attack complex (MAC)
When a complement protein is cleaved, what are the two parts it breaks into?
-A portion (small fragment w/no enzymatic activity, signals activity
-B portion (Large fragment w/ enzyme activity, opsonic, signals activity)
What is the exception to the A and B nomenclature of complement proteins?
C2 (a is the large, b is the small)
Third to act, which complement pathway involves c-reactive protein or antibodies binding to specific antigens on pathogen surface to activate?
C1q binds ________ bound Pentameric IgM molecules while it needs at least ______ bound IgG molecules
*binding of C1q activates C1r which cleaves and activates serine protease C1s
In the classical pathway, C1qr2s2 binds antibodies and cleaves C4 protein which leads to what?
C4b binding to the cell surface
In the classical pathway, C4b does what once bound to the cell surface?
Cleaves C2, forming C4b2a, a C3 convertase
In the classical pathway, C4b2a cleaves C3 to form C4b2a3b, a C5 convertase, leading to what?
Cleaving of C5 into C5b (opsonizes) and C5a (signals)
Second to act, which complement pathway is mannose-binding to pathogen surface?
*Yeast especially contain many terminal mannose residues. Vertebrates have terminal sialic acid residues
The lectin pathway is initiated by mannose binding lectins (MBL) and ficolins and then recruits what two?
MBL associated serine proteases (MASP)
MBL have trimeric clusters of carbohydrate-recognition domains and bind what?
Mannose and fucose residues with high avidity
Ficolins have trimeric clusters of carbohydrate-recognition domains and bind what?
Oligosaccharides containing acetylated sugars
What does MASP-1 and 2 cleave when activated by associating with MBL of ficolin?
*C4b then binds the surface
What is also cleaved by MASP-1 and 2 and then binds with C4b?
*C2a binds with C4b to form C3 convertase C4b2a
In the lectin pathway, C4b2a does what?
Cleaves C3 to C3a and b. C3b bines to the surface or convertase itself
*can cleave up to 1000 molecules of C3
First to act, which complement pathway is activated by pathogen surface creating a local environment conducive to complement?
What are the 3 routes of activation of the alternative pathway?
1-Spontaneous C3 hydrolysis
2-Properdin-pathogen binding and C3 recruitment
3-Proteolytic C3 cleavage (thrombin, clotting cascade proteases)
Exposure of the thioester bond by cleaving C3 is typically of which route of activation for the alternative pathway?
Spontaneous C3 Hydrolysis
*either attacked by H20 to be soluble or C3b binds pathogen surface
What are the two C3 convertases that are responsible for the spontaneous C3 hydrolysis activation of the alternative pathway?
1-iC3Bb (initiates alternative pathway, soluble)
2-C3bBb (drives pathogen C3b opsonization, attached to membrane)
Once bound to C3, B complement is cleaved by what to form iC3Bb?
*Same thing cleaves B to form C3bBb when C3bB is bound to membrane
What protein can bite to C3bBb on pathogen surfaces to stabilize it and drive the reaction forward in the Spontaneous C3 hydrolysis pathway?
Properdin can also bind cell surface, subsequently forming C3bPB by binding C3b and factor B to cleave Factor D, forming C3bPBb as part of of what pathway?
Properdin-Pathogen binding activation of alternative pathway
*C3bPBb is the same as C3bBb from spontaneous C3 hydrolysis once Properdin is bound
What other Complement protein is also activated by the alternative pathway and is cleaved by C3b2Bb?
What 3 things to bound C3b proteins facilitate?
1-Recruitment of inflammatory cells
2-Opsonization of pathogens, facilitating uptake and killing by phagocytes
3-Perforation of cell membrane
Known as anaphylatoxins, the small complement cleavage products do what?
Act on blood vessels to increase vascular permeability and cell-adhesion molecules
*More macrophages, PMNs, and antibodies can then flood the site
When C3b is bound to the bacteria and then binds to Cr1 on a macrophage, what else also must bind to induce phagocytosis?
*act as a checkpoint
Factors H and I both serve what purpose?
Inactivate C3b by cleaving into iC3b
DAF(Decay accelerating factor) and MCP (membrane co-factor protein) serve what purpose?
Disrupt C3 convertase C3bBb on human cell surface
*healthy cells express these, unhealthy cells dont
C5b recruites C6,7,8,and 9 which recruits more C9 to make what?
Membrane Attach Complex (MAC) which forms pores in cell membrane