Pathophysiology of RA

Question 1

How is the synovium affected in RA?

Answer 1

1. pannus - thickened inflammed membrane - inflamed synovial tissue invade + destory articular struc
2. development of new BV
3. influx inflamm cells - T lymphocytes in synovial fluid

Question 2

How are T lymphoycytes contribute to RA?

Answer 2

Activate mature T lymphocytes:

1. present antigen by APC –> T-lymp R
2. Ligand-R-complex (CD80/CD86) on APC bind –> CD 28 -R –> on T lymp -R
3. inflamm cascade activated
4. stimulate relace macro / monocytes –> release inflamm cytokines
5. Activate osteoclasts
6. Activate matrix metalloproteinases / enzymes –> degrade connective tissue
7. stimulate B lymph - produc antibodies

Question 3

How are cytokines contribute to RA ?

Answer 3

1. proteins secreted by cells that serve as intercellular mediators
2. imbalance proinflamm + anti-inflamm cytokines –> inflamm + joint destruction
3. Proinflamm cytokines
   - activate other cytokines
   - adhesion mol respons recruitment lympho
   IL-1, TNF-ALPHA, IL-6, il-7
4. Anti-inflamm cytokines
   - IL4/10 + 1 antagonists
   - not enough to overcome effect of proinflamm cytokines

Question 4

How B lymphocytes contribute to RA?

Answer 4

1. serve APC to T-lymp
2. produce proinflamm cytokines + antibodies
3. Antibodies
   - RF - not present in all RA patients - indicate disease severity
   - Anticitrullinated protein antibodies - ACPA - found early in disease - high - aggressive disease