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Block 7 Week 5 Colt > Immunology of Rheumatoid Arthritis - Hudig > Flashcards

Immunology of Rheumatoid Arthritis - Hudig Flashcards

1
Q

What are the two major aspects of RA in terms of its pathology?

A
  1. synovitis in one or more joints

2. Multiple joints involved

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2
Q

What are the criteria included in RA Dx?

A
  1. serology
  2. number and location of joints involved
  3. elevated APR proteins
  4. duration of symptoms
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3
Q

What are the two common presentations of RA?

A
  1. generalized afternoon fatigue

2. low grade fever, elevated CRP and elevated ESR

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4
Q

What are some of the common symptoms of RA?

A
  1. Morning stiffness >/= 1 hour
  2. Arthritis of >3 joints for >5 weeks
  3. Arthritis in the hands Bone
  4. erosion and decalcification
  5. Synovial fluid turbid, yellow, cells 10-15k with >50% PMNs, no crystals
  6. Generalized afternoon fatigue
  7. Low grade fever, CRP and ESR elevated
  8. Vasculitis, pleurisy pericarditis
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5
Q

What are the five immune cells involved in RA?

A
  1. Dendritic cells
  2. Macrophages
  3. CD4 T cells (Th17 and Tfh)
  4. Plasma b-cells
  5. neutrophils (PMNs)
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6
Q

Which of the cells involved in RA produce TNF-a?

A

DCs and macs

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7
Q

What are the four criteria for autoimmunity?

A
  1. autoantigens involved in disease process
  2. anti-self immunity with immune mediators of damage
  3. immunogenetics
  4. immunotherapeutics
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8
Q

Describe the histological changes to the synovial membrane in RA?

A

formation of finger-like protrusions of the fibrovascular stroma that are inflamed and edematous

  1. villous hypertrophy of synovium
  2. hyperplasia of synoviocytes
  3. chronic inflammation, plasma cells, lymphocytes
  4. lymphoid follicle creation
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9
Q

Are NK cells present in an RA joint?

A

no

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10
Q

Are CD8 T cells present in an RA joint?

A

no

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11
Q

Ultimately, the RA joint synovial membrane forms a (blank) which migrates onto the articular cartilage and underlying bone

A

pannus

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12
Q

There is extensive (blank) of the RA joints that allows for the influx of inflammatory mediators

A

angiogenesis

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13
Q

What cytokines do the DCs release in the RA joint?

A

TNFa and IL6

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14
Q

What is the function of the DCs in the RA joint?

A

Ag presentation

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15
Q

What is the function of the mac’s in the RA joint?

A

cytotoxic and osteoclast bone destruction

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16
Q

What three cytokines do the mac’s release in the RA joint?

A

TNFa, IL6 and IL1

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17
Q

What signals the macrophages to release their cytokines?

A

autoreactive helper T cells

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18
Q

What do the fibroblasts release in response to the macs?

A

MMP and RANKL?

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19
Q

What is the effect on the joint of MMP and RANKL?

A

MMP attacks the tissue and RANKL stimulates osteoclastic destruction of the bone

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20
Q

What two things do the osteoclasts release that cause bone resorption?

A

H+ and cathepsin K

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21
Q

Besides the resident fibroblasts, what infiltrating cell is also stimulated to release RANKL?

A

CD4 T cells

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22
Q

T/F: macrophages express membrane-bound TNF that can also interact with target cells in the joint causing cell death

A

true

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23
Q

What do cells dying from macrophages release?

A

PAD

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24
Q

What two antibodies do the Plasma b cells secrete into the joint?

A

anti-citrullinated peptide antibodies (ACPA) and RF rheumatoid factor

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25
Neutrophils are called into the joint by what chemokine?
IL-17
26
What three things are released from the neutrophil granules as a result of frustrated phagocyotosis?
Collagenase Elastase Proteinase 3
27
The release of neutrophil granule contents into the joint causes the breakdown of (bone/cartilage)
cartilage
28
What is the protease released by macrophages? By neutrophils? What do these break down?
macs: matrix metalloproteinase neutrophils: proteinase 3, elastase, collagenase breaks down the cartilage
29
What cells are destroying the bone? What activated them?
osteoclasts activated by RANKL from macrophages and CD4 T cells
30
What is the Ag for the B cell?
citrulline
31
what two HLA loci are common in RA?
HLA DR*04.01 and DR04.04
32
WHat enzyme converts arginine to citrulline?
PAD: peptidyl arginine deaminase
33
PAD is an (intracellular/extracellular) enzyme
intracellular
34
VIMENTIN in the pannus, collagen, fillaggrin, histones, keratin, and fibrinogen, transglutaminases, vitronectin, aggrecan and PAD itself are the (blanked) proteins in RA
citrullinated
35
What Ig is rheumatoid factor and what is it against?
IgM or IgA anti-Fc IgG
36
RF has low (specificity/sensitivity) for RA
low specificity, can also pick up SLE
37
Anti-citrullinated Abs (ACPA, CCP2, CCP3) have a high (sensitivity/specificity)
specificity of 99%
38
As RA progresses, what happens to the citrulline epitopes?
they can spread to collagen and other proteins which are then recognized as non-self and cause more inflammation
39
Which MHC class presents the citrulline products?
MHC II
40
What is the signal 2 that T cells provide to the B cells for activation?
CD40L
41
What is the signal 2 that the B cells must present to be activated?
B7
42
T/F: one specific helper T cell can stimulate multiple B cells with CD40L
true
43
T/F: one specific B cell presenting a citrullinated Ag may activate many T cells with B7
true
44
T/F: Asymptomatic individuals with RA can have anti-CCP Abs
true
45
How do you calculate positive predictive value?
number of postive results with Dz present divided by total positive results (Dz absent and present)
46
How do you calculate negative predictive value?
number of negative results with Dz absent divided by total number of negative results (Dz present and absent)
47
How do you calculate sensitivity?
number of positive results with Dz present divided by number of pos and neg results of Dz present
48
How do you calculate specificity?
Number of negative results with Dz absent divided by number of negative positive and negative result in Dz absent
49
Glucocorticoids reduce the production of which cytokines?
TNFa and IL1
50
Methotrexate reduces (blank and blank) cell expansion
B and T cell
51
Biological agents bock which cyotkines?
TNFa and IL6
52
What are the two general biological agent strategies?
1. bind to the cytokine itself | 2. block the cytokine receptor
53
What are the two ways you can use a biological to bind to the cytokine itself?
1. with mAb to the cytokine | 2. with fusion protein made of Fc IgG with cytokine receptor
54
mAb binding to the cytokine receptor can support (blank) to kill the receptor-bearing cell
ADCC
55
mAb binding to the cytokine receptor can modulate receptors of the cell to (blank) it
disable it
56
Blockade of which two cytokines is effective in treating RA
IL6 and TNFa
57
Does blockade of TNF-a or IL6 have a lower risk of reactivating latent TB?
IL6
58
Which cytokine blockade is more effective in monotherapy without MTX?
IL6
59
which bDMARD is a Fc-fucsion protein with the p75 TNF receptor?
Etanercept
60
What are the targets of Etanercept?
TNF-a and lymphotoxin
61
(Infliximab/Adalimumab) is a mouse-human chimeric mAb?
Ifliximab
62
(Infliximab/Adalimumab) is a human mAb
Adalimumab
63
(Certerlizumab pegol/Adalimumab) is a Fab humanized, pegylated mAb
Certerilizumab
64
What is the target of infliximab?
TNFa
65
Whatis the target of adaliumumab and certerlizumamb?
TNF-a
66
T/F: anti-TNF agents can bind transmembrane TNF
true
67
T/F: all anti-TNF agents can cause ADCC
false; certolizumab pegol cannot
68
What is the only anti-TNF that cannot cause ADCC, apoptosis, and PMN death?
certolizumab
69
T/F: anti-TNF agents can inhibit transmembrane cytokine cleavage
true
70
Which two Anti-IL6 agents target the IL6 receptor?
tocilizumab and sarilumab

Block 7 Week 5 Colt (7 decks)

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