complement cascade

Question 1

3 complement paths

Answer 1

1. classical
2. alternative
3. lectin

Question 2

role of complement in innate immune response

Answer 2

-opsonin, inflammation, cytolysis, eliminates Ag-Ab complex

Question 3

lysis

Answer 3

-lyse cells, bacteria, & viruses
-major effector of the humoral branch of immune system
-MAC

Question 4

opsonization

Answer 4

promotes phagocytosis of particulate Ags

Question 5

binding to specific complement receptors on cells of immune system

Answer 5

-trigger specific cell functions (inflammation)
-secretion of immunoregulatory molecules

Question 6

immune clearance

Answer 6

-removes immune complexes from circulation
-deposits immune complexes in the spleen & liver

Question 7

anaphylatoxin

Answer 7

-C3a, C4a, & C5a
-bind to complement receptors on mast cells & basos to induce degranulation
-induce smooth muscle contractions, increase vascular permeability, extravasion & chemoattraction (C3a, C5a & C5b67)

Question 8

main osponin of complement

Answer 8

C3b binds surface of microbes
-C4b & iC3b can also osponize

Question 9

viral neutralization

Answer 9

-formation of viral aggregates reduces the net number of infectious particles
-deposits of Ab & complement on viral particles neutralizes infectivity by blocking viral attachment

Question 10

source & atomic location

Answer 10

-soluble proteins produced by the liver
-present in blood, lymphatics, & ECM

Question 11

complement activation

Answer 11

cascade of enzymatic reactions where each protease cleaves & activates the next protease in the pathway

Question 12

role of RBCs in complement

Answer 12

deliver the Ag-Ab complex to the liver & spleen for consumption by phagocytes

Question 13

classical pathway

Answer 13

-starts with C1q (18 peptides that can form trimers)
-C1 & C1r/C1s make dimeric pairs
-C1qr2s2 binds 2 immunoglobulins
-once 1 IgM binds, C1qr2s2 folds to bind more
-must have high IgG concentrations
-C1qr2s2 is bound, C1r converts to C1[r]
-C1[r] converts C1s to C1[s]
-C1[s] cleaves C2 & C4
-C4 cleaved into C4a & C4b (C4b + C2)
-C2 gets cleaved by C1[s] = C[4b2a], a C3 convertase
-C3b can join C[4b2a] and make C[4b2a]3b, a C5 convertase

Question 14

classical pathway activation

Answer 14

formation of Ag-Ab complex

Question 15

alternative pathway activation

Answer 15

-inhibited by cell surface constituents that are foreign to host
-Ab-independent

Question 16

lectin pathway activation

Answer 16

-binding of mannose binding lectin (MBL) to mannose residues on glycoproteins or carbs on microorganisms surface
-Ab-independent

Question 17

has
no
spleen

Answer 17

haemophiles- mostly in kids prior to H. flu vaccine
neisseria - you’re dead
strep pneumonia- most infectious, 57% sepsis, 59% death

Question 18

alternative pathway

Answer 18

-does not depend on pathogen binding for activation
-C3bBb convertase
-initiated through spontaneous hydrolysis of C3
-C3 exists in high concentrations & contains thiolester with spontaneous cleavage
-C3b can bind bacteria & enhance phagocytosis
-C3 convertase contains C3b & creates positive feedback
-factor H displaces B, inactivating the convertase

Question 19

4 fates of C3b

Answer 19

-bind microbial surface
-associate with factor B
-associate with factor H
-bind another C3b

Question 20

MAC formation in alternative pathway

Answer 20

-C5 convertase cleaves C5 into C5a and C5b. ​
-C5b is unstable and is stabilized by C6.​
-C5b6 allows C6 and C7 to associate and penetrate a membrane. ​
-The C5b67 recruits C8 which organizes C9 to form a “membrane attack complex” (MAC).

Question 21

MBL pathway

Answer 21

MBL: acute phase protein which binds mannose residues on glycoproteins or carbs. increases during inflammation
MASP-1 & MASP-2: MBL associated serine proteases
-Has no spleen organisms can activate
-resembles classical: C4 & C2 to produce activated proteins
-works the same as C1q
-MASPs cleave C4 & C2 forming C3 convertase
-continues to form C5 convertase & MAC

Question 22

lectin definition

Answer 22

proteins that bind to carbs

Question 23

protecting normal cells from complement

Answer 23

-MCP or CD46 accelerates C3b, CD46, Factor H & Factor I to prevent excess alternative pathway activation
-DAF accelerates destruction of C3 convertase
-CD59 (protectin) prevents incorporation of C9 to inhibit MAC formation

Question 24

iC3b

Answer 24

inactive form of C3b
-opsonin

Question 25

complement activating immunoglobulins

Answer 25

IgM, IgG1, IgG2, human IgG3

Question 26

CFT for what antibodies

Answer 26

heterophile

Question 27

complement deficiencies

Answer 27

abnormalities in C5 or higher cytokines can lead to autoimmune disorders (lupus)