Quiz 8 Flashcards
What are 3 inflammatory cytokines?
TNF-a
IL-1B
IL-6
What is TNF-a main function?
master regulator
What is IL-1B main function?
fever response
What is IL-6 main function?
produces acute phase proteins
What cell produces the inflammatory cytokines?
macrophages
______ is required for production of IL-1B and IL-6
TNF-a
TNF-a increases what 2 things?
vascular permeability
adhesion molecules
What inflammatory cytokine activates macrophages?
TNF-a
What are acute phase proteins?
proteins in the blood that increase or decrease in concentration in response to an infection
What is an example of an acute phase protein?
CRP (activates complement)
What are the 2 steps of activation for IL-1B?
priming
activation
What happens during the priming step of IL-1B?
- PRR recognizes PAMP/DAMPs
- secretion of TNF and IFN
- production of pro-IL-1B
What happens during the activation step of IL-1B?
- inflammasome activates caspace
- pro-IL-1B cleaved into IL-1B
What 2 things are special about IL-1B?
- no gene transcription is required to make it
- cannot leave the cell unless leakage occurs
What are 3 functions of neutrophils?
- phagocytosis
- degranulation
- NETosis
What do neutrophil nets contain?
LL-37 (AMP)
histones
proteases
DNA
Why do neutrophil nets have proteases?
go into nucleus and cleaves chromatin
What does PAD4 do?
de-condenses chromatin by changing charge on Arg causing histones to release DNA
What is the synovial membrane?
allows nutrients and cell exchange between joints and blood
What is the problem cell in the synovial membrane?
FLS
When immune cells infiltrate the synovium, it swells and become a __________
pannus
What 3 things is inside an inflamed synovium (pannsu)
- macrophages
- osteoclasts
- invasive FLS
___________ produce MMP that destroy bone
Osteoclasts
____________ produce MMP that destroy cartilidge
FLS
What activates osteoclasts and FLS?
TNF-a
IL-1B
IL-6
What are 3 risk factors for RA?
- HLA-DRB1
- smoking
- microbiota
What are 3 initiation factors of RA?
- CRP circulation
- post-translational modification (citrullination)
- auto-Ab (ACPAs and RF)
What is rheumatoid factors?
high affinity auto-IgG directed against Fc of other IgG resulting in IgG appearing pathogen (immune complex)
What is a type III HSR?
abnormal immune response mediated by the formation of immune complexes
How does a type III HSR turn into RA?
immune complexes form and travel to joints
What is citrullination?
changing charge on Arg from positive to neutral making it look pathogenic
What performs citrullination?
PAD4
Where does citrullination occur?
neutrophils
What activates PAD4?
pore forming toxins produced by bacteria
HLA-____ individuals increase risk of developing auto-Abs
DRB1
What are ACPAs?
anti-citrullinated protein antibodies
How are ACPAs made?
bacterial toxin and MAC targets neutrophils causing increased exposure of neutrophils DNA = creation of ACPA
How does smoking increase chances of getting RA?
increase cell damage = increased PAD2 = increased citrullinated protiens = more ACPA
What is epitope spreading?
Ab recognizes different epitopes on the same protein causing the creation of many types of auto-Abs
How does epitope spreading occur?
chronic immune activation leads to increased numbers of auto-Ab specificity (more antigens presented = more antibodies)
How does TNF-a induce RA?
increases vascular permiability allow immune cells/complexes to travel the body
TNFα can induce formation of osteoclasts
Why are anti-TNF-a good RA drug?
prevents immune cells/complexes from traveling because TNF-a usually increases vascular perminability
Why is blocking PAD4 useful as a therapeutic?
prevents citrullinated proteins from being created (no antigen now)
Why is it useful that anti-PAD4 drugs are oral?
difficult to have type III HSR because no large complex can be made
