Complement Class 1 Flashcards
What is complement?
a complex series of more than 30 soluble and cell-bound proteins that interact in a very specific way to enhance host defense mechanisms against foreign cells
The Discovery of Complement
- by Jules Bordet, early 1890s
- Sheep antiserum against Vibrio cholerae was no effective if heated above 56 degrees
- ABs not denatured at 56 degrees
- Must be second component
- Added AB depleted serum to heated sera-restored lytic activity
- “complements” activity of AB
Where are more plasma complement proteins synthesized?
in the liver, with the exception of C1 components, which are mainly produced by intestinal epithelial cells, and factor D, which is made in adipose tissue
What are zymogens?
Inactive precursor proteins that are converted to active enzymes in the complement system
ex -
What are the three different ways complement can be activated?
Classical pathway, Alternative pathway, Lectin pathway
Classical pathway (Complement activation)
which involves nine proteins that are triggered by antigen–antibody combination
- originally called properdin system
- activated by IgM,IgG1-4, IgA, IgE - few substances can bind complement directly to initiate the classical cascade
Alternative pathway (Complement activation)
antibody-independent means of activation of complement
Lectin pathway (complement activation)
another antibody-independent means of activating complement proteins Its major constituent, mannose- (or mannan-) binding lectin (MBL), adheres to mannose found mainly in the cell walls or outer coating of bacteria, viruses, yeast, and protozoa.
What are the functions of complement?
- major role in inflammatory reponse against foreign antigens
- end product is lysis of invading cell
- complements the functions of the innate and adaptive immune systems
- Lysis, opsonization, activation of the inflammatory response, clearance of immune complexes
How are complement components named?
Primary Proteins - named on a numeric system Additional components - given a factor name Activated proenzymes - once cleaved, the smaller components have “a or b” added
Anaphylatoxin
a small peptide that causes increased vascular permeability, contraction of smooth muscle, and release of histamine from basophils and mast cells
Ex - C3a, C4a, C5a
chemotaxin
A protein or other substance that acts as a chemical messenger to produce chemotaxis.
Opsonin
Serum proteins that attach to a foreign substance and
enhance phagocytosis (from the Greek word meaning “to prepare
for eating”).
What are the three main stages of complement activation?
Recognition unit (C1), activation unit (C4,2,3), membrane attack complex/terminal sequence (C5-9)
What are the components of the Recognition unit of the complement cascade?
C1qrs is the recognition unit that binds to the FC portion of two antibody molecules. C1s is activated and cleaves C4 and C2 to form C4b2a
(C1qrs + ABs FC –> C1s activation –> C4 and C2 cleavage –> C4b2a)
What changes happen to the structure of the C1rqs during the change from inactive to active?
Structure of C1qrs. When two or more globular heads of C1q attach to bound immunoglobulin molecules, the collagen like stalks change their configuration.
The resulting shape change causes C1r to become a serine protease, which cleaves a small fragment of C1s, uncovering the C1s protease, whose only targets are C4 and C2.
What are the components of the Activation unit of the complement cascade?
C4b2a, also known as C3 convertase –> cleaves C3 to form C4b2a3b (aka C5 convertase) the combination of C4b2a3b is the activation unit
Terminal sequence of Complement components
- common to all activation pathways
- C5 convertases cleave C5 into C5a and C5b
compare C5a to C3a. Why is one more potent than the other?
Membrane Attack complex
Circular polymer of C9 molecules that for a pore in cell surface
Pores allow free ion and water exchange leading to osmotic swelling and cell rupture
What are the characteristics / determining factors of the classical pathway?
1 - Initiated by binding of antibody
2 - C1q proteins link bound antibody molecules by binding sugar residues on Fc region of IgG and IgM molecules
(Cannot bind to just one antibody molecule-needs to bridge molecules - 2 or more IgG monomers/ 1 pentameric IgM complex)
(C1q is not enzymatic)
3 - Requires association of other serine proteases C1r and C1s”
How does IgM binding influence the Classical pathway?
Cannot bind in “planar” conformation is serum
Only binds to “staple” conformation bound to cells
Anaphylatoxin
“a small peptide that causes increased vascular permeability, contraction of smooth muscle, and release of histamine from basophils and mast cells Ex - C3a, C4a, C5a”
