lecture 26 Flashcards
1
Q
What are learning objectives?
A
- what is synovium, and what is normal function?
- what cell types are present in healthy synovium and what are their functions?
- describe how healthy synovial tissue is transformed in RA?
- what are the functions of the cells within the inflamed synovium in RA?
- what are tNF, IL-1 and IL-6 and what do they do?
- why is the use of animal models important in the pre-clinical study of RA pathogenesis?
- identify 2 pre-clinical models of RA and discuss their pros and cons
2
Q
What is the synovium?
A
- thin membrane that extends from skeletal tissue at interface of cartilage and bone and lines the capsule of diarthrodial joints
3
Q
What is the healthy structure of synovium?
A
intima (synovial lining layer)
- interface between the joint cavity and the subintima
- 1-3 cell layers deep
- cells = synoviocytes
subintima (sublining layer)
- connective tissues that become denser closer to the joint capsule
- contains blood vessels, lymphatic vessels and nerves
4
Q
What would we see on a healthy biopsy of synovium?
A
- 3 different types of synovial tissue that differ by histological appearance
areolar
- intima: continuous layer of lining cells
- sub-intima: capillaries immediately below, small arterioles and venules and lymphatic vessels
fibrous
- close to ligaments or tendons, or close to bone/cartilage margins
- layer of cells on ligament or tendon, difficult to distinguish from fibrocartilage
fatty
- found mostly in fat pads
- underlying the intima is superficial net of capillaries amongst the apidocytes (fat cells)
5
Q
What are the functions of a health synovium?
A
- facilitates movement between non-deformable structures within joint (e.g. bone/cartilage surfaces)
- synovium highly deformable, freely mobile
- non-adherent properties (i.e. not stick to bone and cartilage)
- slips seemlessly over cartilage/bone matrix
- provision of lubricants that minimuse “wear and tear” on joint tissues
- hyaluronan (high molecular weight polysaccharide maintains synovial fluid viscosity, effective shock absorption, prevents fluid loss from joint space under loading)
- lubricin (mucin-like proteoglycan, protects cartilage surfaces from protein deposition and cell adhesion; inhibits synovial cell growth)
- contributes to formation of synovial fluid
- chondrocyte nutrition via solute diffusion from synovial fluid
6
Q
What is hyaluronanan?
A
high molecular weight polysaccharide maintains synovial fluid viscosity, effective shock absorption, prevents fluid loss from joint space under loading
7
Q
What is lubricin?
A
mucin-like proteoglycan, protects cartilage surfaces from protein deposition and cell adhesion; inhibits synovial cell growth
8
Q
Is cartilage vascular?
A
no
9
Q
What are the cell populations in the intima?
A
2 distinct cell populations
- 20% cells are macrophage-like synoviocytes (type A synoviates
- 80% cells are fibroblast-like synoviocytes (type B synoviocytes)
10
Q
What are macrophage-like synoviocytes?
A
- type A synoviocytes
cell function
- primarily phagocytic cells
- important for clearance of debris in joint express receptors for Fc domains of IgG (recognition of immune complexes)
11
Q
What are fibroblast-like synoviocytes?
A
type b
cell function:
- produce lubricin and hyaluronan (joint lubrication)
- produce collagen and fibronectic (extracellular matrices important for cell adherence)
12
Q
What is the target tissue for inflammation in RA?
A
- synovium
- becomes aggressive like tissue
- infiltration of inflammatory cells
- release of factors that cause destruction of cartilage and bone
13
Q
What characterises RA?
A
- inflammation and swelling of multiple joints
- synovitis
- e.g. metacarpals
- MRI: healthy joint you see nice clear black spaces in the joints of the hand, RA - bright areas, inflammation tissue
artheroscope:
- jelly like substance
- inflamed synovial tissue
histologic:
- bone and cartilage no longer one intact tissue
- expanded intima layer
- large amounts of inflammatory cells
- formation of new blood vessels
14
Q
What is pannus?
A
- inflamed synovial tissue next to cartilage/bone - pannus (latin for “cloth” or “covering”) - inflamed synovial tissue that “creeps” over the cartilage and bone tissue of the joint
- i.e. the synovial tissue ‘really’ adjacent to cartilage and bone
- differs histologically from inflamed synovial tissues away from bone/cartilage
- rich in fibroblast-like cells
- contains macrophages
- contains fewer immune cells (B, T, sometimes mast) than the “peripheral” inflamed synovial tissue
- creates hypoxic micro-environment
- cells within the pannus release factors –> destroys articular cartilage and bone
15
Q
What is inflammation of the synovium?
A
- occurs very early in the disease
- synovial lining (intima) expands –> up to 12 cells
- cell proliferation (hyperplasia)
- infiltration of inflammatory cells into the sublining (subintima): macrophages, T cells, B cells, neutrophils (less common)
- formation of new blood vessels (neovascularisation)
- ectopic lymphoid neogenesis
- deposition of fibrin in active disease (long standing or severe disease)
16
Q
Do you see neutrophils?
A
- not so common in synovium but yes in synovial fluid
17
Q
How are cells recruited into the RA synovium?
A
In RA synovium:
- cells present within the inflamed synovial tissue secrete factors:
1) attract inflammatory cells into the joint (chemokines)
2) retain the cells there (adhesion molecules)
18
Q
What are cell types important in the pathogenesis of RA?
A
- fibroblast
- macrophage
- T cell
- B cell
