lecture 7

Question 1

zymogens

Answer 1

pro enzymes
components exist as this
highly conserved bw specifies

Question 2

complement system initiated through 4 distinct pathways

Answer 2

w identical end results

1. classical
2. alternative
3. MBL
4. C2 bypass pathway: intracellular activity

Question 3

complement system plays a role in both

Answer 3

innate and adaptive immunity

Question 4

complement proteins secreted in Liver by Macrophages as

Answer 4

zymogens and are found in normal serum

Question 5

innate pathway

Answer 5

includes alternative and lectin pathways

activated by recognizing PAMPS

Question 6

adaptive pathway

Answer 6

includes classical pathways

activated by presence of antibody bound to antigen

Question 7

complement components (C3b) bind

Answer 7

covalently to invading microbes and opsonize them

Question 8

membrane attack complex

Answer 8

complement components that punch holes in microbes

Question 9

chemoattractants trigger

Answer 9

inflammation through C3a C5a

Question 10

deficiences of some components can lead to

Answer 10

increased susceptibility to infections

Question 11

major proteins designated as

Answer 11

C1-C9

Question 12

lectin pathway

Answer 12

triggered by mannose-binding lectin - MBL
revognizes mannose on microbial glycoproteins and glycolipids
uses C4 & C2
creates C3 components (C3b and C3a)
C3 deposited on microbe and opsonization/phagocytosis starts
C5 converts to C5a and b - comes in and form attack on membrane

Question 13

C3a

Answer 13

inflammation

Question 14

C5a

Answer 14

inflammation

Question 15

alternative pathway

Answer 15

triggered by direct recognition of certain microbial surface structures (ex: spontaneous cleavage of thioester bond in C3)
B and C3
creates C3a and b components which generate C5a and C5b
attack on membrane by complement proteins!

Question 16

classical pathway

Answer 16

uses C1 protein to detect IgM, IgG1, or IgG3 antibodies bound to the microbe
uses C4 and C3
creates C3a and b components which generate C5a and C5b
attack on membrane by complement proteins!

Question 17

MAC formation

Answer 17

C6 + C5b + C7 + C8 binds C9 units together to make membrane attack complex to cause cell lysis
initiated by lectin, alternative and classical pathways

Question 18

C1q

Answer 18

complement activating protein

binds w C1r2s2 onto microbial surface antigen bound to IgM antibody

Question 19

mannose binding lectin

Answer 19

complement activating protein

binds MASP1/2 to mannose on microbe surface

Question 20

MASP

Answer 20

MBL- associated serine protease

Question 21

Ficolin

Answer 21

complement activating protein

binds MASP1/2 to N acetylglucosamine on bacterial cell wall

Question 22

mannose binding lectin

Answer 22

complement initation mechanisms
mannose binding lectin (MASP1/2) binds mannose/similar sugars on bacteria, fungi, protozoa & viruses -> conformational change -> C4 and then C2 cleavage -> generates C4a + C2a -> generate C4bC2b convertase -> cleave C3 -> makes C3a + C3b

Question 23

antibodies as complement initiation mechanism

Answer 23

antibodies bind to epitopes on pathogens surface -> conformational change -> C1q (like MBL) binds to complement binding site on antibodies w C1r & C1s which are serine proteases -> C4 & then C2 cleavage -> make C4a + C2a -> generate cell bound C4bC2b convertase -> cleaves C3 -> makes C3a + C3b

Question 24

C1r & C1s

Answer 24

serine protease - cuts C4 and C2

Question 25

spontaneous C3 cleavage as complement initation mechanism

Answer 25

C3 spontaneous breakdown -> C3b + C3a -> C3b surface bound -> a. normal circumstance (no avtivating surfaces) -> Hv binds and creates C3bH -> I inactivates C3b b. in presence of activating surface B binds to create C3bB -> D acts on it and makes C3bBb + C3bBa -> P acts on it and makes C3bBbP

Question 26

C3 convertases as complement initiation mechanism

Answer 26

1. C4b2b | 2. C3bBb

Question 27

C5 convertases as complement initation mechanism

Answer 27

1. C4b2b3b | 2. C3bBb3b

Question 28

regulation of complement activation

Answer 28

C1, decay accelerating factor (DAF) (CD55), CD59, factor H and I

Question 29

C1 inhibitor

Answer 29

disrupts C1 and the classical pathway

Question 30

decay accelerating factor

Answer 30

DAF, CD55 | dissociates C3 convertases and lectin pathway

Question 31

factor H and I

Answer 31

destroy C3b on sialic acid experssing cells | disrupts alternative pathway

Question 32

CD59

Answer 32

blocks C9 | prevents C5b678 + poly C9 so no MASP or membrane attack

Question 33

C3b and sialic acid

Answer 33

C3 breaks down spontaneously into C3a and C3b, if it is bound to sialic acid factor H will bind to C3b -> activates factor 1 which creates a complex that degrades C3b -> a. iC3b b. C3c and C3d C3c, C3d and iC3b are opsongens that are unable to initiatiate complement pathway

Question 34

CR1

Answer 34

CR1 + C3b in RBC, monocytes, macrophages, neutrophils and T cells immune adherence receptor removal of C3b opsonized immune complexes by liver neutrophil phagocytosis inhibition of classical and alternative pathways

Question 35

CR2

Answer 35

CR2 + iC3b/C3d (g) in B cells enhances B cell immunity

Question 36

CR3

Answer 36

CR3 + iC3B dimer in NK cells, monocytes, macrophages, neutrophils and T cells ``` adherence receptor cell-cell interaction and binding phagocytosis leukocyte trafficking and migration outside in signaling promote inflammation ```

Question 37

CR4

Answer 37

CR4 + iC3b dimer in neutrophils, NK cells, monocytes, macrophages, dendritic cells ``` same as CR3 adherence receptor cell-cell interaction and binding phagocytosis leukocyte trafficking and migration outside in signaling promote inflammation ```

Question 38

consequences of complement activation

Answer 38

1. complement mediated cytolysis 2. opsonization and phagocytosis 3. stimulation of inflammatory reactions 4. regulate B cell responses

Question 39

complement mediated cytolysis

Answer 39

binding of C3b to microbe surface and activate late components of complement formation of MAC osmotic lysis of microbe

Question 40

opsonization and phagocytosis of complement activation

Answer 40

binding of C3b (or C4b) to microbe - opsonization recognition of bound C3b by phagocyte C3b receptor (CR1) phagocytosis of microbe!

Question 41

stimulation of inflammatory responses as result of complement activation

Answer 41

proteolysis of C3, C4, C5 to release C3a, C4a, and C5a recruitment and activation of leukocytes by C3a, C4a and C5a microbe is DESTROYED by leukocytes

Question 42

B cell responses regulated as consequence of complement activation

Answer 42

C3d bound to antigen, binds to BCR and CR2 C3b cleaved by factor 1 C3c + C3d regulate B cell responses

Question 43

complement deficiencies

Answer 43

1. canine C3 | 2. procine factor H

Question 44

canine C3 deficiency

Answer 44

brittany spaniels autosomal recessive C3 deficiency experience recurrent sepsis, pneumonia, wound infections - recurrent bacterial infections organisms: clostridium, pseudomonas, e coli, klebsiella species treatment: antibiotics and monitoring

Question 45

porcine factor H deficiency

Answer 45

yorkshire pigs factor H inactivates C3b -> prevents excessive alternative pathway activation autosomal recessive deficiency renal failure at early age (glomerulonephritis) treatment: infusion of normal swine serum C3 will deposit in glomerulus - causing renal failure

Question 46

Neisseria meningitides

Answer 46

resistance to complement activation (alternative pathway) | mechanism of immune evasion: sialic acid expression inhibits C3 and C5 convertases

Question 47

streptococcus

Answer 47

resistance to complement activation (alternative pathway) | mechanism of immune evasion: M protein blocks C3 binding to organism, and C3b binding to complement receptors

Question 48

evasion of innate immunity by microbes

Answer 48

1. salic acid expression 2. M protein block 3. capsule preventing interation w C3b 4. some bacter inactivate C3a and C5a 5. produce molecules that mimic regulatory proteins