E1.2 RA

Question 1

Name some symptoms of RA

Answer 1

~affects joints symmetrically 
Hand deformities 
Rheumatoid nodule 
Rheumatoid vasculitis (extra-articular)

Question 2

Symptoms of RA

describe symptoms if untreated

Answer 2

Fatigue, flu like feeling swollen and tender joints and morning stiffness

• serious systemic manifestations, includes pleural effusions,
• lung nodules, and interstitial lung disease.
• lymphomas and vasculitis and small to medium arteries,

Question 3

What is elevated in RA

Answer 3

C reactive protein, increased erythrocyte sedimentation rate

Question 4

Establishment of auto immune disease requires which 2 separate events

Answer 4

Genetic predisposition of the patient: leads to the generation of autoreactive T&B cells.
2. Triggering event ~environmental stimulus: viral, bacteria, infections or tissue injury.
- This allows the activated phagocytes or APCs to activate previous autoreactive Tc, resulting in disrupted
tolerance.

Question 5

Triggering events leads to (broad summary of events)

Answer 5

• immune response against auto-antigens
• Inflammation in our joint.
• Formation of granulation tissue and this is referred to as pannus
• The erosion of bone and cartilage and joint destruction.
  ((Family history of RA gives a three to five times more likely to develop the disease.))

Question 6

Antibodies in rheumatoid arthritis

Answer 6

Activation of auto-reactive Bc - targeted for elimination

• RF: IgG-Fc (rheumatoid factor - pentameric: bind to Fc of IgG (69%) cases
• citrullinated proteins (ACPA): bind to citrullinated protein residues of many self proteins (e.g. Collagen II, histotones, fibrinogen)
• collagen type I

Question 7

Which immune cells contribute to RA

Answer 7

APC 
B cells 
Plasma cells
Ig – Antibodies
Th cells
CD4 
Memory Bc

Question 8

Are both Tc & Bc involved

explain roles

Answer 8

Yes
Tc: activate macrophages and other cells
(Tc move to synovium interact with macrophages)
Bc: Ab production & in activating Tc through antigen-presentation (present antigen to Tc, modulate Tc and induce function, induce cytokines)

Question 9

Name the inflammatory cytokines and their role?

Answer 9

IL-1, IL-6, IL-21, IL-23, TGF-B

- recruit neutrophils, activate our B-cells & promote osteoclastgenesis: in synovial joints

Question 10

What cells are recruited in chronic inflammation

Answer 10

(Influx of immune cells to the site of injury/infection)

• Macrophages are recruited: produce potent vasoactive mediators (+ resistant macrophages)
• Other leukocytes: produce lipid mediators & cytokines,
• Lymphocytes (B & Tc): release Ab & cytokines
• Resident cells such as synovial fibroblasts: release proteases & inflammatory cytokines

Question 11

Describe macrophage cellular events in RA

Answer 11

Engulf & process antigen.
Synthesise pro-inflammatory agents;
Release prostaglandins due to COX-2 induction.
They release TNFα & IL-1 to stimulate fibroblasts

Question 12

Describe Leukocyte cellular events in RA

Answer 12

Production mediated by increased levels of IL-3, GM-CSF, M-CSF and G-CSF.
Leukocytes are directed into inflamed joint synovium

Question 13

Describe Lymphocyte cellular events in RA

Answer 13

B-cells secrete immunoglobulin involved in complement activation, and immune complexes.
Secrete INFγ, IL-2 and IL-4 which stimulate formation of more lymphocytes

Question 14

Describe Synovial fibroblast cellular events in RA

Answer 14

Mitosis triggered by macrophages (IL-1 & TNFα) causing a vast increase in numbers.
Stimulated to secrete cartilage destroying enzymes (MMPs), and synthesize scar tissues.

Question 15

Describe cytokine cellular events in RA

Answer 15

Such as IL-1 and TNFα stimulate the endothelium to express adhesion molecules and to release prostaglandins into the synovium