L8 complement system

Question 1

what kind of response is the complement?

Answer 1

innate humoral response

Question 2

bordet’s experiment: non-immunized serum with bacteria = …

Answer 2

no effect

Question 3

bordet’s experiment: immunized serum with bacteria = …

Answer 3

lysis

Question 4

immunized serum + heat + bacterium = ….

Answer 4

no effect

Question 5

immunized serum + heat + non-immunized serum + bacterium = …

Answer 5

lysis

Question 6

what kind of proteins is the complement system compromised of?

Answer 6

soluble plasma proteins and membrane-bound proteins

Question 7

what cells are complement proteins synthesized by?

Answer 7

1. hepatocytes (liver cells), main producers
2. fibroblasts
3. epithelial cells
4. monocytes
5. macrophages

Question 8

what are the seven functional categories of complement components?

Answer 8

1. initiators
2. enzymatic inhibitors
3. phagocytosis-enhancing components/opsonins
4. inflammatory mediators
5. membrane attack proteins
6. complement receptors
7. regulatory complement components

Question 9

what do initiators do?

Answer 9

initiate complement reactions,
bind to soluble or membrane-bound molecules,
binds to their ligand causing conformational changes = activation

Question 10

what are enzymatic mediators, and what do they do?

Answer 10

cleave proteins (most enzymatic mediators are proteolytic enzymes) to activate = zymogens

Question 11

what do opsonins do?

Answer 11

enhance phagocytosis through binding to the complement receptors on the surface of phagocytic cells

Question 12

what do inflammatory mediators do?

Answer 12

they are smaller cleavage products, and bind to receptors on endothelial cells of blood vessels increasing capillary diameter. they also bind to receptors and attract other cells (chemotaxis)

ex. C3a and C5a

Question 13

what do membrane attack proteins do?

Answer 13

form the membrane attack complex (MAC). they insert themselves in the membranes of microorganisms to punch holes leading to lysis. they can also form on the surface of infected cells

Question 14

what are complement receptors, and what are the effects of binding to these receptors?

Answer 14

abbreviated as “CR”, bind to complement proteins and signal specific cell functions. they can enhance phagocytosis, cell activation, induce degranulation, chemotaxis, and clearance of immune complexes

Question 15

what do regulatory complement components do?

Answer 15

prevent unintended complement-mediated damage of host cells
ex. factor 1 degrade complement components to prevent deposition of components

Question 16

what are the 3 major pathways of complement activation?

Answer 16

1. classical pathway
2. lectin pathway
3. alternative pathway

Question 17

what are the 3 major steps in the pathways of complement activation?

Answer 17

1. initiation
2. amplification
3. termination

Question 18

what do all three pathways lead to?

Answer 18

all converge to generation of the C3 and C5 convertases

Question 19

what do convertases do?

Answer 19

convert C3 and C5 to their active forms

Question 20

what are the steps in the classical pathway?

Answer 20

1. C1q binds antigen-bound antibody. C1r activates auto-catalytically and activates the second C1r; both activate C1s
2. C1s cleaves C4 and C2. Cleaving C4 exposes the binding site for C2. C4 binds the surface near C1 and C2 binds C4, forming C3 convertase
3. C3 convertase hydrolyzes many C3 molecules. some combine with C3 convertase to form C5 convertase
4. the c3b component of C5 convertase binds C5, permitting C4b2a to cleave C5
5. C5b binds C6, initiating the formation of the MAC

Question 21

how does the lectin pathway work?

Answer 21

instead of antibodies, the lectin pathway is initiated through the binding of lectins (MBL, ficolins)

Question 22

how is C3 convertase produced in the lectin pathway?

Answer 22

1. activated MASP-2 associated with MBL or ficolin cleaves C4 to C4a and C4b, which binds to the microbial surface
2. C4b then binds to C2, which is cleaved by MASP-2, to C2a and C2b, forming the C4b2a complex = C3 convertase

Question 23

how is C5 convertase created?

Answer 23

C3b binds to C4b2a

Question 24

what is the alternative pathway?

Answer 24

1. C3b is deposited by classical or lectin pathway C3 convertase
2. C3b binds factor B
3. bound factor B is cleaved by plasma protease factor D into Ba and Bb
4. C3bBb complex is a C3 convertase, cleaving many C3 molecules to C3a and C3b

Question 25

what are the C3 convertase of each pathway?

Answer 25

classical : C4b2a alternative: C3bBb lectin: C4b2a

Question 26

what are the C5 convertases of each pathway?

Answer 26

classical: C4b2a3b alternative: C3bBb3b lectin: C4b2a3b