Quiz 2 Part 3

Question 1

What is the purpose of an inflammasome

Answer 1

By means of an inflammasome, activated macrophages can increase their production of IL-1B

Question 2

What is the function of IL-1B? What other cytokine has the same function?

Answer 2

to make blood vessels more permeable
TNF-a

Question 3

How is an inflammasome assembled?

Answer 3

the uptake of ATP and release of potassium ions

Question 4

Explain how an inflammasome helps to generate massive amounts of IL-1B

Answer 4

IL-1B cytokine that was originally made binds to a toll-like receptor on a macrophage. this triggers a series of reactions leading to the transcription and translation of IL-1B (an inactive form called pro-IL-1B)

A NOD-like receptor called NLRP3 oligomerizes and binds to an adaptor protein. procaspase-1 (inactive form) binds to this complex and becomes activated.

Caspase 1 then removes itself from this NLRP3/adaptor protein complex and cleaves pro-IL-1B, producing the active cytokine, IL-1B

This newly formed IL-1B leaves the macrophage and repeats the cycle by continually binding to the TOLL-like receptor on the macrophage, leading to the transcription and translation of an inactive form of IL-1B, producing massive amounts of IL-1B

Question 5

What are the first effector cells recruited to the site of infection?

Answer 5

neutrophils

Question 6

what percent of hematopoietic activity is dedicated to neutrophil production?

Answer 6

60%

Question 7

Neutrophils have receptors for…

Answer 7

chemokines— CXCL8 and C5a

Question 8

Neutrophils are ___ lived

Answer 8

SHORT LIVED. they dies within hours of entering tissue. Pus is actually dead neutrophils

Question 9

What is the 2 step process of neutrophils in the immune response?

Answer 9

1. Recruitment (chemoattraction, leukocyte rolling, extravasation)
2. Pathogen recognition, engulfment, and destruction

Question 10

How do neutrophils destroy bacteria and fungi?

Answer 10

neutrophils bind them, engulf, and destroy them with the toxic contents of neutrophil granules

Question 11

Which can recognize more pathogens – neutrophils or macrophages?

Answer 11

neutrophils

Question 12

How are neutrophils migrated to the site of infection?

Answer 12

Endothelial cells express SELECTINS in response to vasodilation and inflammatory cytokines.
Selectin interacts with carbohydrates on neutrophils causing “leukocyte rolling”, slowing the neutrophil gradually along the endothelium

TNFa then induces expression of ICAM-1 and ICAM-2 which bind to integrin receptors on neutrophils. This bond is initially weak, but is strengthened by CXCL8 binding to CXCR1 and CXCR2 on neutrophils. Neutrophil is now VERY TIGHTLY BOUND.

Then, TNFa and IL-1B increase the space between the gap junctions and allow the neutrophil to undergo extravasation and reach the infected tissue. Once in the tissue, the neutrophil follows the gradient of CXCL8 to reach the site of infection

Question 13

Why is chemokine concentration higher at the site of infection?

Answer 13

because macrophages at the site of infection are producing them through the activation of NFKB

Question 14

diapedesis is the term for…

Answer 14

the neutrophil going through the gap junctions

Question 15

Do neutrophils have one or 2 purposes? what about macrophages?

Answer 15

neutrophils have ONE purpose - phagocytosis
macrophages have TWO purposes - phagocytosis and the production of cytokines to recruit neutrophils

Question 16

What is the dominant phagocytic cell at the site of infection?

Answer 16

neutrophils

Question 17

Neutrophils contain ______ types of granules that fuse with phagosomes:

Answer 17

3:
primary (azurophilic)
secondary (specific)
tertiary (gelatinase)

Question 18

Name some substances that primary granules contain

Answer 18

lysozyme
defensins
myeloperoxidase
neutral proteases (function at a neutral pH)

Question 19

Name some things that secondary granules contain

Answer 19

lactoferrin
lysozyme (also in primary!)
several membrane proteins
**COMPONENTS OF NADPH OXIDASE

Question 20

Tertiary granules contain….

Answer 20

gelatinase —- protease containing metal which sequesters iron and inhibits bacterial growth

Question 21

What is the meaning of primary secondary and tertiary granules

Answer 21

the order in which the neutrophils make them

Question 22

Explain the process of destruction by neutrophils

Answer 22

1st, the bacterium is phagocytosed by the neutrophil (gradient of CXCL8 has already been followed to the site of infection)

then, the newly formed phagosome fuses with azurophilic and specific granules.

The pH of the phagosome rises, the antimicrobial response is activated, and the bacterium is killed. The pH rises because neutral proteases which are present in primary lysosomes cannot function at a low pH.

Then, the pH of the phagosome goes back down. The lysosome fuses with the phagosome and initiates acid hydrolysis to completely degrade the pathogen

Lastly, the neutrophil dies by apoptosis and is phagocytosed by the macrophage.

Question 23

Which are larger—macrophages or neutrophils?

Answer 23

macrophages

Question 24

What is chronic granulomatous disease?

Answer 24

a condition in which a person lacks NADPH oxidase genes. This leads to chronic intracellular infection

Question 25

What happens if a person lacks IKK subunit?

Answer 25

This is termed NEMO deficiency
-NFKB activity is impaired
-Macrophages cannot be induced through TLR4