Chapter 3

Question 1

What is the function of NADPH oxidase contained in secondary granules?

Answer 1

NADPH oxidase produces superoxide radicals that are converted into H2O2 (hydrogen peroxide) by superoxide dismutase

Question 2

“NADPH oxidase produces superoxide radicals that are converted into hydrogen peroxide by superoxide dismutase”

What is the result of these reactions?

Answer 2

These reactions rapidly consume Hydrogen ions and have the direct effect of raising the pH of the phagosome.
This is useful because antimicrobial peptides and proteins (enzymes in the granules) are activated at a high pH and attack the trapped pathogen

Question 3

What happens after the antimicrobial peptides and proteins attack the trapped pathogen in the phagosome?

Answer 3

the pH returns to neutral. Lysosomes fuse with the phagosome and allow complete breakdown of the pathogen.

Question 4

Besides the rapid consumption of H+, what else do these reactions consume?

Answer 4

they transiently consume O2. This is called the “respiratory burst” which powers the neutrophil’s ferocious intracellular attack

Question 5

What are the products of this respiratory burst? What do they do?

Answer 5

The products of this respiratory burst are toxic oxygen species. These toxic oxygen species breakdown bacterial cells

Question 6

Besides the toxic oxygen species that are products of the respiratory burst, what other toxic species are involved?

Answer 6

toxic products can ALSO diffuse out of the neutrophil and damage neighboring cells

Question 7

What limits the extent of damage done by hydrogen peroxide?

Answer 7

CATALSE degrades H2O2, limiting damage

Question 8

Are superoxide radicals and H2O2 damaging to human cells?

Answer 8

YES - they both are

Question 9

Is hydrogen produced or consumed in the respiratory burst?

Answer 9

CONSUMED – that’s how the pH rises

Question 10

Which enzyme degrades H202

Answer 10

CATALSE — very efficient enzyme with a high turnover rate

Question 11

During the respiratory burst, how many O2 molecules are produced and how many are consumed?

Answer 11

2 oxygen molecules are consumed and 1 is produced

Question 12

What happens once granule contents are consumed?

Answer 12

the neutrophil dies

Question 13

How many mechanisms of neutrophil death are there? name them

Answer 13

2:

Apoptosis (programmed cell death)
Netosis — neutrophil extracellular traps.

NET’s contain defensins, proteases, and calprotectin which trap microorganisms and kill them, even after the neutrophil itself is dead.

NET’s cause the neutrophil nucleus to swell and burst. The chromatin dissolves and is extruded from the cell

Question 14

What is the effect of IL-1/IL-6/TNFa on the liver?

Answer 14

IL-1/IL-6/TNFa cause the liver to make ACUTE PHASE PROTEINS: C-reactive protein and mannose-binding lectin

Question 15

C-reactive protein and mannose-binding lectin are part of….

Answer 15

an alternative way to activate complement and “ramp up” the response. Part of Lectin pathway

Question 16

What are C-reactive protein and mannose-binding lectin also known as?

Answer 16

acute phase proteins

Question 17

What effect does IL-1/IL-6/TNFa have on the bone marrow and endothelium?

Answer 17

IL-1/IL-6/TNFa cause the bone marrow to initiate Neutrophil mobilization in times of infection. Extra neutrophils are housed in the bone marrow/endothelium. When given the “word” from IL-1/IL-6/TNFa, they “dump” more neutrophils into the bloodstream

Question 18

What is the ultimate effect of the liver producing acute phase proteins (C-reactive protein, mannose-binding lectin)

Answer 18

Activation of complement and opsonization

Question 19

What is the ultimate effect of neutrophil mobilization by the bone marrow and endothelium?

Answer 19

greater phagocytosis

Question 20

What effect does IL-1/IL-6/TNFa have on the hypothalamus?

Answer 20

Increased body temp (fever)

Question 21

WHY does IL-1/IL-6/TNFa cause the hypothalamus to raise the body temperature and cause a fever?

Answer 21

because high temperatures favor eukaryotic cell division over prokaryotic. decreases viral/bacterial replication

Question 22

What effect does IL-1/IL-6/TNFa have on fat and muscle?

Answer 22

IL-1/IL-6/TNFa cause fat and muscle (particularly near the site of infection) to increase protein synthesis and the hydrolysis of ATP which raises the temperature of the cells surrounding the infection. (keep in mind: inflammasome formation is affected) raise in temp also reduces bacterial/viral replication

Question 23

Local inflammation can produce _____ effects by the actions of _____

Answer 23

local inflammation can produce SYSTEMIC effects by the actions of inflammatory cytokines

Question 24

What is the common function between C-reactive protein, LPS, and mannose-binding lectin?

Answer 24

PATHOGEN RECOGNITION

Question 25

The complement components — C3, C4, C9.. are all involved in…..

Answer 25

pathogen elimination

Question 26

Which 2 blood plasma proteins increase in concentration dramatically during the acute-phase response?

Answer 26

C-reactive protein and Serum amyloid A

Question 27

What is MBL? (mannose-binding lectin)

Answer 27

a calcium dependent acute-phase protein with 18 potential sites of attachment to a pathogen’s surface (carbohydrate recognition)

Question 28

How many stalks are there on mannose binding lectin? Each stalk is made up of…

Answer 28

there are 6 (or 5) stalks on mannose binding lectin. Each stalk is composed of 3 identical polypeptides

Question 29

What happens when mannose-binding lectin binds to a pathogen?

Answer 29

The Lectin pathway of complement activation is induced

Question 30

What are the names and functions of the 2 zymogens (inactive proteases) that associate with mannose binding lectin in the plasma?

Answer 30

MASP-2 and MASP-1

MASP-2 is a serine protease that cleaves C4 and C2

MASP-1 is a protease but its function is unknown

Question 31

Explain full the Lectin pathway of complement activation

Answer 31

Activated MASP-2 cleaves C4 into C4a and C4b.
Some C4b covalently binds to the microbial surface.

Then, MASP-2 cleaves C2 (functionally equivalent to factor B) into C2a and C2b. C2a binds to the surface C4b (already on the pathogen from before). This forms the CLASSICAL C3 CONVERTASE: C4bC2a.

This classical C3 convertase (C4bC2a) can then cleave a C3 molecule into C3a and C3b. due to close proximity, the C3a will most likely “tag” the microbial surface

THIS CAN ALSO FORM THE ALTERNATIVE C5 CONVERTASE!!!!!

Question 32

recap: what is the alternative C3 convertase? What is the classical C3 convertase?

Answer 32

alternative C3 convertase: C3bBb
Classical C3 convertase: C4bC2a

Question 33

Both the classical and alternative C3 convertase do what?

Answer 33

cleave C3 to tag the pathogen with C3b. Both can also form the alternative C5 convertase

Question 34

CRP (C-reactive protein) can activate….

Answer 34

the CLASSICAL pathway of complement activation

Question 35

Explain the structure and function of C1

Answer 35

C1 is structurally similar to MBL. It has a bouquet of 6 C1q subunits and 2 each of C1r and C1s proteases.

CRP (PENTRAXIN FAMILY) binds to the pathogen surface and interacts with complement protein C1

Question 36

C-reactive protein is a member of the ___ family

Answer 36

pentraxin

Question 37

Explain how CRP functions to tag a pathogen

Answer 37

When C1 (structurally similar to MBL) binds to CRP, the classical pathway of complement fixation is activated. C reactive protein with C1 on top binds to some substance on the pathogen membrane (ie: phosphorylcholine). Then, C4 binds to the complex and cleaves it into C4b and C4a. C4b serves as a “tag” on the pathogen surface

Question 38

Explain how the classical complement pathway feeds into the lectin pathway.

Answer 38

C4b that has been tagged in the classical pathway can also form the classical C3 convertase (C4bC2a) that is also formed in the lectin pathway. From there, everything collapses back into C3

Question 39

In total, C1 has ____ molecules of proteases

Answer 39

4 total
2 C1r and 2 C1s