Quiz 8

Question 1

What are 3 inflammatory cytokines?

Answer 1

TNF-a
IL-1B
IL-6

Question 2

What is TNF-a main function?

Answer 2

master regulator

Question 3

What is IL-1B main function?

Answer 3

fever response

Question 4

What is IL-6 main function?

Answer 4

produces acute phase proteins

Question 5

What cell produces the inflammatory cytokines?

Answer 5

macrophages

Question 6

______ is required for production of IL-1B and IL-6

Answer 6

TNF-a

Question 7

TNF-a increases what 2 things?

Answer 7

vascular permeability
adhesion molecules

Question 8

What inflammatory cytokine activates macrophages?

Answer 8

TNF-a

Question 9

What are acute phase proteins?

Answer 9

proteins in the blood that increase or decrease in concentration in response to an infection

Question 10

What is an example of an acute phase protein?

Answer 10

CRP (activates complement)

Question 11

What are the 2 steps of activation for IL-1B?

Answer 11

priming
activation

Question 12

What happens during the priming step of IL-1B?

Answer 12

1. PRR recognizes PAMP/DAMPs
2. secretion of TNF and IFN
3. production of pro-IL-1B

Question 13

What happens during the activation step of IL-1B?

Answer 13

1. inflammasome activates caspace
2. pro-IL-1B cleaved into IL-1B

Question 14

What 2 things are special about IL-1B?

Answer 14

1. no gene transcription is required to make it
2. cannot leave the cell unless leakage occurs

Question 15

What are 3 functions of neutrophils?

Answer 15

1. phagocytosis
2. degranulation
3. NETosis

Question 16

What do neutrophil nets contain?

Answer 16

LL-37 (AMP)
histones
proteases
DNA

Question 17

Why do neutrophil nets have proteases?

Answer 17

go into nucleus and cleaves chromatin

Question 18

What does PAD4 do?

Answer 18

de-condenses chromatin by changing charge on Arg causing histones to release DNA

Question 19

What is the synovial membrane?

Answer 19

allows nutrients and cell exchange between joints and blood

Question 20

What is the problem cell in the synovial membrane?

Answer 20

FLS

Question 21

When immune cells infiltrate the synovium, it swells and become a __________

Answer 21

pannus

Question 22

What 3 things is inside an inflamed synovium (pannsu)

Answer 22

1. macrophages
2. osteoclasts
3. invasive FLS

Question 23

___________ produce MMP that destroy bone

Answer 23

Osteoclasts

Question 24

____________ produce MMP that destroy cartilidge

Answer 24

FLS

Question 25

What activates osteoclasts and FLS?

Answer 25

TNF-a IL-1B IL-6

Question 26

What are 3 risk factors for RA?

Answer 26

1. HLA-DRB1 2. smoking 3. microbiota

Question 27

What are 3 initiation factors of RA?

Answer 27

1. CRP circulation 2. post-translational modification (citrullination) 3. auto-Ab (ACPAs and RF)

Question 28

What is rheumatoid factors?

Answer 28

high affinity auto-IgG directed against Fc of other IgG resulting in IgG appearing pathogen (immune complex)

Question 29

What is a type III HSR?

Answer 29

abnormal immune response mediated by the formation of immune complexes

Question 30

How does a type III HSR turn into RA?

Answer 30

immune complexes form and travel to joints

Question 31

What is citrullination?

Answer 31

changing charge on Arg from positive to neutral making it look pathogenic

Question 32

What performs citrullination?

Answer 32

PAD4

Question 33

Where does citrullination occur?

Answer 33

neutrophils

Question 34

What activates PAD4?

Answer 34

pore forming toxins produced by bacteria

Question 35

HLA-____ individuals increase risk of developing auto-Abs

Answer 35

DRB1

Question 36

What are ACPAs?

Answer 36

anti-citrullinated protein antibodies

Question 37

How are ACPAs made?

Answer 37

bacterial toxin and MAC targets neutrophils causing increased exposure of neutrophils DNA = creation of ACPA

Question 38

How does smoking increase chances of getting RA?

Answer 38

increase cell damage = increased PAD2 = increased citrullinated protiens = more ACPA

Question 39

What is epitope spreading?

Answer 39

Ab recognizes different epitopes on the same protein causing the creation of many types of auto-Abs

Question 40

How does epitope spreading occur?

Answer 40

chronic immune activation leads to increased numbers of auto-Ab specificity (more antigens presented = more antibodies)

Question 41

How does TNF-a induce RA?

Answer 41

increases vascular permiability allow immune cells/complexes to travel the body TNFα can induce formation of osteoclasts

Question 42

Why are anti-TNF-a good RA drug?

Answer 42

prevents immune cells/complexes from traveling because TNF-a usually increases vascular perminability

Question 43

Why is blocking PAD4 useful as a therapeutic?

Answer 43

prevents citrullinated proteins from being created (no antigen now)

Question 44

Why is it useful that anti-PAD4 drugs are oral?

Answer 44

difficult to have type III HSR because no large complex can be made