ImmunoSero Lec (Midterms - Soluble Mediators) Flashcards
Part of the innate system that helps phagocytic cells to clear pathogens, lyse foreign cells, opsonize and tag invaders for clearance, direct the adaptive immune system to the site of infection.
Complement system
Amplify inflammatory response having 30 soluble and cell bound proteins
Complement system
Heat labile substance present in normal nonimmune serum
Complement system
Complement activation is also considered pro-inflammatory in its ability to (3)
- Increase vascular permeability
- Recruit monocytes and neutrophils
- Trigger secretion of regulatory molecules that amplify the immune response
In the pro-inflammatory role, this serves as an important link between innate and adaptive immunity
complement protein
A complex series composed of 30 soluble and cell bound proteins that interact in a very specific way to enhance host defense mechanisms against foregin cells including serum proteins, serosal proteins, and cell membrane receptors
Complement protein
This is where most plasma proteins are synthesized except C1
Liver
C1 are components which are mainly produced by these cells.
Intestinal epithelial cells
Tissue composition of Factor D of Alternative Pathway
Adipose tissue
Nobel prize laureate which elucidated their nature
Jules Bordet
Coined the term “complement” because it complements the action of antibody in destroying microorganisms.
Paul Erlich
3 Complement pathways
- Classical
- Alternative
- Mannose Binding Lectin
Originally called the properdin system, because the protein properdin was thought to initiate this pathway. However, it is know that properdin’s major function is to stabilize a key enzyme complex formed along the pathway.
Alternative Pathway
Oldest pathway which is another antibody-independent means of activating complement proteins.
Mannos Binding Lectin Pathway
The major constituent of the MBL Pathway that adheres to mannose found mainly in the cell walls or outer coating of bacteria, viruses, yeast, and protozoa.
Mannos- (mannan-) binding lectin
Naming system
- Designated as “b”
- Designated as “a”
b: larger fragment
a: smaller fragment
In this complement protein, “a” is designated as the larger fragment while “b” is the smaller fragment.
C2
Number of proteins triggered by antigen-antibody combination in the Classical Pathway
9 (C1-C9)
Immunoglobulins involved in the Classical Pathway
IgM, IgG1, IgG2, and IgG3
Initiation of Classical Pathway
- Antibody binding to the pathogen
- C1 protein binding to the FC receptor of antibody
Most efficient because it has multiple binding sites thus it takes only one molecule attached to two adjacent antigenic determinants to initiate the cascade.
IgM
Number of IgG molecules that must attach to antigen within 30 to 40 nm of each other before complement can bind.
At least how many IgG molecules would it tkae to ensure that it is close enough to initiate such binding?
2 IgG molecules;
At least 1000
Within the IgG group, IgG3 is the most effective, followed by these two:
IgG 1 then IgG2
Stablizes C1q, C1r, and C1s.
Calcium
First complement component of the classical pathway to bind.
C1
The ________________ unit is the part that binds to antibody molecules, whereas the ____________________ subunits generate enzyme activity to begin the cascade.
C1q;
C1r and C1s
Composed of 6 strands that forms the 6 globular heads with collagen tailed portion. This structure has been likened to a bouquet with six blossoms extending outward
C1q
As long as this is present in the serum, C1r and C1s remain associated with C1q
calcium
Recognizes the fragment crystallizable region of two adjacent antibody molecules.
C1q
At least how many globular heads of C1q must be bound to initiate the classical pathway?
two
Binding for IgG and IgM respectively
IgG - CH2 region
IgM - CH3 region
Once this complement is activated, the recognition stage ends
C1s
This complement is extremely specific because its only known subtrate is C1s
C1r
A complement that has a limited specificity with it only subtrates being C4 and C2
C1s
Formed by C4a + C2b
C4b2a (C3 convertase)
Second-most-abundant complement protein with a serum concentration of approximately 600 ug/mL.
C4
C1s cleaves C4 to split off how many amino acid fragment called C4a?
77-amino-acid fragment
C4b binds mainly to antigen in cluster that are within this radius of C1
40 nm radius
First amplification step in the cascade (The Activation Unit)
C4b binds to antigen in cluster that are within 40 nm radius of C1
For every one C1 attached, approximately how many molecules of C4 are split and attached?
30
Closely associated with the gene for factor B (alternative pathway) on Chromosome 6
C2
True or False.
C2 has a short half-life that serves to keep the reaction localized.
True
Written as C4b2a to indicate that complex is an active enzyme by which its half-life is estimated to be between 15 seconds - 3 minutes.
C3 convertase
Major and central constituent of the complement system
C3
a powerful opsonin
C3b
Most significant step in the entire process of complement activation
Cleavage of C3 to C3b
Half-life estimation of C3b if not bound to antigen.
60 microseconds
Written as C4b2a3b
C5 convertase
When this attaches to the cell membrane, formation of the (MAC) Membrane Attack Complex begins.
C5b
Most significant biological consequences of the complement system.
Splitting of C5 and the cleavage of C3
Forms the Membrane Attack Complex
C6-C9
The MAC is the complex of
C5b-C6-C7-C8-C9
In MAC, if the complex is soluble in circulation, it is called …
sC5b-9
Functional pore size of completed MAC unit which would allow ions to pass in and out of the membrane.
70 to 100A
This form of IgM is found in plasma
Planar form
Form of IgM that will bind to the cell
Staple form
Recognition unit
C1
activation unit
C2, C4, and C3
