Lecture 5: The Complement System

Question 1

Complement system

Answer 1

Plasma proteins that work together to opsonize microbes, promote the recruitment of phagocytes, and, in some cases, to directly kill the microbe

Question 2

C3a involved in

Answer 2

Inflammation, by acting as a chemoattractant for neutrophils

Question 3

C3b involved in

Answer 3

Opsonization and phagocytosis- attaches to microbial surface

Question 4

C5a involved in

Answer 4

Inflammation- it is a potent chemoattractant that also induces changes in permeability of blood vessels

Question 5

Early step 1

Answer 5

Formation of C3 convertase complexes that produce C3a and C3b which trigger inflammation and opsonization

Question 6

Early step 2

Answer 6

Formation of C5 convertase complexes that produce C5a and C5b which perpetuate inflammation and initiate late steps

Question 7

Late steps

Answer 7

Formation of MACs which form holes in microbial membranes

Question 8

Complement activation involves

Answer 8

Proteolytic cascades in which a zymogen is altered to become and active protease that cleaves the next complement

Question 9

C5 convertase formed from

Answer 9

C3b and C3 convertase

Question 10

C5b

Answer 10

Attaches to bacterial membrane and initiates formation of a complex of C6-C9 proteins, forming MAC

Question 11

MAC

Answer 11

Membrane attack complex

Multiple MACs cause bacterial leak and lysis

Question 12

Alternative pathway Auto-activation and Tickover

Answer 12

Alternative pathway is capable of autoactivation because of “tickover” of C3, which spontaneously generates C3a and C3b

Question 13

C3b and Factor B

Answer 13

C3b is capable of binding factor B which can be cleaved into Ba and Bb by protease factor D

Question 14

Bb associates with

Answer 14

Bb associates with C3b, forming C3bBb (Alternative pathway C3 convertase), which can then cleave additional C3 molecules creating more C3b

Question 15

Properdin

Answer 15

Stabilizes protein:protein interactions during the process of auto-activation and “tickover” in the alternative pathway

Question 16

Alternative pathway amplification loop

Answer 16

Alternative pathway can be initiated as an amplification loop when fixed C3b that was generated by classical or lectin pathway activation binds Factor B

Question 17

Classical pathway mediated by

Answer 17

Antibodies

Question 18

Steps in classical pathway up to C3 convertase

Answer 18

C1q binds to Fc portion of Ig, activating C1r which activates C1s
C1s activates C2 and C4 into C2a/b and C4a/b
C4b joins C2a to form C4bC2a (C3) convertase
C3 convertase cleaves C3–> C3a/b
C3b joins C4bC2a complex to form C5 convertase

Question 19

Lectin pathway

Answer 19

Activated MASP-2 cleaves C4 to C4a/b
C4b binds to microbial surface
MASP-2 also cleaves C2 to C2a/b
C3a binds to surface C4b forming classical C3 convertase
C3 convertase cleaves C3 to C3a/b
C3b binds microbial surface

Question 20

Lectin pathway C5 convertase consists of

Answer 20

C4bC2aC3b

Question 21

What triggers the lectin pathway

Answer 21

Mannose binding lectin (MBL)

Question 22

MBL function

Answer 22

Recognizes terminal mannose residues on microbes

Activates zymogens MASP1 and MASP2

Question 23

Alternative pathway differences from classical

Answer 23

C3 undergoes spontaneous hydrolysis
Factors B and D are needed
C3bBb is the C3 convertase
C3bBbC3b is C5 convertase

Question 24

Lectin pathway differences from classical

Answer 24

Does not use C1
When MBP binds to bacteria, MASPS are activated
Same convertases as classical

Question 25

T or F: Compliment system may be activated on surface of mammalian cells

Answer 25

False, they express regulatory proteins that inhibit, disassemble or cleave the convertases

Question 26

DAF function

Answer 26

Blocks C2-C4b interaction

Question 27

DAF or CR1 enhance what

Answer 27

Dissociation of C4bC2a interaction

Question 28

CR1 and Factor I (FI) function

Answer 28

Cleave C4b and C3b

Question 29

FI is also known as (think of its function)

Answer 29

C3b/C4b inactivator

Question 30

Inflammatory effects of C3a

Answer 30

Some contraction of smooth muscles and increased permeability of blood vessels
Degranulation of basophils

Question 31

Inflammatory effects of C5a

Answer 31

Strong contraction of smooth muscles and permeability of blood vessels
Degranulation of basophils
Chemotaxis, release of O2 radicals and lysosomal enzymes

Question 32

TNF and IL-1 act on

Answer 32

Act locally on leukocytes and endothelium to induce acute inflammation, and induce the expression of IL-6 from leukocytes and other cells

Question 33

TNF, IL-1 and IL-6 work together to mediate

Answer 33

Mediate protective systemic effects of inflammation (fever, APP synthesis, leukocytosis)

Question 34

Side effect of systemic TNF

Answer 34

Can cause pathologic abnormalities that lead to septic shock

Question 35

CRP and SAP are

Answer 35

APPs

Question 36

Plasma concentration of CRP and SAP in healthy individual

Answer 36

Concentrations are low but can increase 1000-fold during infection

Question 37

What synthesizes SAP and CRP and what stimulates synthesis

Answer 37

Synthesized by liver, stimulated by IL-1 & IL-6

Question 38

CRP recognizes

Answer 38

Phosphorylcholine on bacteria

Question 39

SAP recognizes

Answer 39

Phosphatidylethanolamine on apoptotic cells

Question 40

SAP and CRP can activate

Answer 40

Complement system by binding C1q and activating classical pathway

Question 41

What stimulates production of IFN-a and IFN-b

Answer 41

TLR mediated signaling which activates IRF transcription factors

Question 42

IFN-a/b function on infected cells

Answer 42

Bind to receptors on infected cells inducing the expression of genes whose products enhance the cells susceptibility to CTL-mediated killing

Question 43

Function of IFN-a/b on uninfected cells

Answer 43

INF-a/b produced by infected cells can bind to receptors on uninfected cells, activating JAK-STAT pathway which activates genes whose products interfere with viral replication

Question 44

Signal one for the activation of lymphocytes is caused by

Answer 44

Ag recognition by B cells

Question 45

Signal two for the activation of lymphocytes

Answer 45

Molecules induced by innate immune responses to microbes provide signal two