module 08 section 04 (alternative pathway)

Question 1

what is unique about the alternative complement pathway? (2)

Answer 1

• it is continuously activated at a low level

- it does not involve the classical or lectin activation pathways

Question 2

recall: what is the alternative pathway initiated by?

Answer 2

various pathogens and particles of microbial origins (e.g. gram-neg bacteria, lipopolysaccarides, fungal cell walls, etc.) and some non-pathogenic material (e.g. IgG, IgA, IgE aggregates, polymers, etc.)

Question 3

what is step 1 of the alternative pathway?

Answer 3

• a continuously low rate of spontaneous cleavage of C3 occurs in the plasma
• this cleavage results in C3b and C3a
• there’s two possible outcomes for C3b

Question 4

intact C3 contains what?

Answer 4

a concealed thioester group (R-S-CO-R’)

Question 5

what happens during C3 cleavage that results in two possible outcomes for C3b?

Answer 5

during C3 cleavage the C3a chain is cleaved by C3 convertase, leaving the previously concealed thioester group exposed in C3b

Question 6

what are the possible fates of C3b?

Answer 6

(1) in the fluid phase C3b is inactivated by hydrolysis
or
(2) covalent attachment of C3b to a protein (microbe or cell surface protein) or a polysaccaride via thioester linkage

Question 7

what is step 2 of the alternative pathway?

Answer 7

• come C3b binds to the microbial cell surface via active thioester bond
• factor B then binds C3b

Question 8

what is step 3 of the alternative pathway?

Answer 8

factor D cleaves factor B (which is still bound to C3b)

Question 9

what is step 4 of the alternative pathway?

Answer 9

• properdin (aka factor P) stabilizes the C3bBb complex

- stabilized complex now called C3 convertase

Question 10

what is step 5 of the alternative pathway?

Answer 10

cleavage of an additional C3 molecule by cell-associated C3bBb (C3 convertase), giving C3a and C3b

Question 11

what is step 6 of the alternative pathway?

Answer 11

binding of the additional C3b to the cell surface forms a C3bBbC3b complex called C5 convertase

Question 12

what is step 7 of the alternative pathway?

Answer 12

• C5 convertase cleaves C5 into C5b

- recall C5b is the end product of each of the complement activation pathways

Question 13

why is it important to understand all three complement activation pathways?

Answer 13

so that you can understand the redundancy in the killing process

Question 14

in additon to the shared end product, C5b, is there another protein shared by the pathways?

Answer 14

yea - C3

Question 15

recap: what happens once C3 is activated (cleaved)?

Answer 15

C3b is the active part of the protein (helps kill cells via opsonization and recruits C5, 6, 7, 8, and 9 to kill cells via lysis initated by MAC attack), while C3a often becomes anaphylactic leading to inflammation

Question 16

explain classroom 142, lecture 42, focused on classical or developmental biology analogy

Answer 16

• classroom = classical - C1 cleaved, then C4, then C2 = C3 activation
• lecture = lectin - C4 cleaved followed by C2 = C3 activation
• classical vs developmental reminds you that the subject alternates = alternative - classical = C3b, developemntal = factor D, biology = factor B - all involved in C3 activation

Question 17

what are the activators for the classical, lectin, and alternative pathways?

Answer 17

classical: Ag-Ab complex
lectin: MBL-Mannose complex
alternative: spontaneous hydrolysis of C3

Question 18

what is C3-convertase composed of in the classical, lectin, and alternative pathways?

Answer 18

classical: C4bC2a
lectin: C4bC2b
alternative: C3bBb

Question 19

what is C5-convertase composed of in the classical, lectin, and alternative pathways?

Answer 19

classical: C4bC2aC3b
lectin: C4bC2aC3b
alternative: C3bBbC3b

Question 20

which component(s) of complement could be missing and still leave the remainder of the complement system capable of activation by the alternative pathway?

Answer 20

C1, C2, and C4