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Molecule to Malady > Lecture 26 - Synovium in health and RA > Flashcards

Lecture 26 - Synovium in health and RA Flashcards

1
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

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2
Q

The first layer f the synovium is

A

Intima

tissue between the joint cavity and subintima
1-3 cell layers deep (cells=synoviocytes)

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3
Q

The second later of synovium is..

A

Subintima

connnective tissue that becomes denser closer to the joint capsule

contains BV, Lymph.Vs, and nerves

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4
Q

The Areolar section is bit _____ from the joint, the Fibrous section is where the ____ is and is difficult to distringuish from ______

The Fatty section is mostly in fat pads,

A

Areolar section is bit further from the joint, the Fibrous section is where the joint is and is difficult to distringuish from fibrocartilage

all have Subintima and Intima

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5
Q

What are the functions of the synovium?

A

Facilitiates movement

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6
Q

What provision of lubricants exist to to minimuse “wear and tear: on joint tissues?

A

Hyaluronan - shock absorbtion, prevents fluid loss

Lubricin - proteoglycan, protects cartilage surfaces from protein desposition and cell adhesion, and inhibits cell overgrowth

The “Grease” within your joints

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7
Q

___ of cells are Macrophage-like synovocytes in intima

A

20% - phagocytic capability

others are Fibroblast-like synoviocytes

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8
Q

Which type of synoviocytes produces Hyaluronan and Lubricin?

A

Fibroblast-like synoviocytes

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9
Q

___is when the inflamed synovial tissue is next to cartilage

A

pannus

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10
Q

True or False

RA inflammation; you will see neutrophils in synovial fuid

A

False

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11
Q

There will be infiltration of infalmmatory cells into the sublining, as well as formation of new…

A

blood vessels (neovascularisation)

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12
Q

True or False

Inflammationof the synovium occurs late in disease

A

False

happens early

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13
Q

Cells present within the inflammed synovial tissue secrete factors which:

A

1 ) attract inflammatory cells into the joint (chemokines)

2) retain the cells there (adhesion molecules)

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14
Q

Pannus is..

A

the inflammed synovial tissue that “creeps’ over the cartilage and bone tissue of the joint

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15
Q

True or False

Pannus contains macrophages but fewer T/B cells than the peripheral inflammed synovial tissue

A

true

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16
Q

Cells within the pannus release factors which..

A

destroy articular cartilage and bone

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17
Q

In RA Type _ (macrophage) synoviocytes outnumber type _ (fibroblast-ike) cells

A

In RA Type A (macrophage) synoviocytes outnumber type B (fibroblast-ike) cells

usually type A are only 20%

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18
Q

There will be high expression of _____ markers and ______ from type A synovioocytes

A

There will be high epression of phagocytic markers and MHC II from type A synovioocytes

19
Q

Synovial macrophages may trans-differentiate” to a ____ -resorbing osteoclast

A

bone

20
Q

Type B cells respond to infammation with ____

A

cytokines including IL-1, TNF, IL-6

chemokines

MMPs

factors that promote local bone destruction

21
Q

What factors promote local bone destruction?

A

TNF and RANKL

22
Q

___are the most prominant CD4+ T cells

A

TH17 - express IL-17

23
Q

___ _____T cells are most prevalent in RA synovium

A

Cd4+ helper T cells

24
Q

TH17 cells are recreited and differentiate upon signalling by..

A

IL-6 (from the macrophage)

25
Q

Th17 are large sources of

A

RANKL - bone destruction

26
Q

In RA ___ cells are not functoin - leading to reduced expression of IL-10 and IL-4

A

T regs

27
Q

True or False

The presence and distribtion of B cells is fixed among RA patients

A

False - it is varialbe

May depend on stage of disease

28
Q

What is responsible for the antibodu production in response to T cell cativation and production of autoantibodies (eg. RA factor and anti-CCP)

A

B cells

29
Q

Moleules belonging to the categories of

cytokines
chemokines
growthfactors

are all released in

A

RA synovium and contribute to RA pathogenesis

30
Q

TNF is..

family of _____

Initially membrane bound, is cleaved by ___ (both forms are active)

A

Tumour necrosis factor

family of cytokines

Initially membrane bound, is cleaved by TACE (both forms are active)

31
Q

what are the 2 receptors for TNF and how are they expressed?

A

TNFR1

TNFR2 - expression is induced (particularly in inflammatory situations)

32
Q

TNF can have local and ___ actions

A

systemic

33
Q

What role does TNF play in RA?

A

Proinflammatory cytokine release

Hepcidin induction

PGE

Osteoclast activation

Chondrocyte activation (cartilage destruction)

Angiogenesis

Leukocyte accumulator

Endothelial cell activation

Chemokine release

34
Q

IL-1has two forms..

A

IL-1 aplha - cytosolic form

IL-1 beta - inducible form, secreted and then cleaved into its active form by ICE

35
Q

Il-1 activity is tightly regulated by ______ inhibitors

A

endogenous inhibitors

36
Q

IL-1 receptor antagonist called ____ competes with IL-1 for binding to IL-1 receptor

A

IL-1ra

It is the balance of the cytokine and the inhibitor that determines the effect of IL-1 signalling

37
Q

What is IL-1’s role in RA

A

activation of leukocytes, endothelial cells and synovial fibroblasts

induce expression of chemokines and cytokines

Induce MMP production by chondrocytes

Induce expression of osteoclasts

38
Q

IL-6 is responsible for

A

increasing acute phase response in liver

Induces Ig production in B cells

promotes differentiation of TH17 cells

induces cytokine production by synovial fibroblasts and macrophages

promote osteoclasts (RANKL)

39
Q

The most common model for screening therapeutic compounds is ___

A

Collagen induced arthritis (CIA)

40
Q

What are the pros of Rodent collagen-induced arthritis models?:

____arthritis affecting knee and paws

______ inflammation

dependent on __ cells

___ and __-beta expression is elevated
(inhibition of either of these cytokines, _____ arthritis onset and severity)

__ factor reported to be produced

A

symmetrical arthritis affecting knee and paws

synovial inflammation

Dependent on T/B cells (also requires the expression of MHC II alleles)

TNF and IL-beta expression is elevated
(inhibition of either of these cytokines, reduces arthritis onset and severity)

RF factor reported to be produced

41
Q

What are the cons of Rodent collagen-induced arthritis models?:

Disease susceptibily is depends on expression of certain classes of _____
only certain mouse strains are susceptible (_____ most susceptible)

_____ of disease onset and severity of disease can be variable

unlike RA patients Collagen _____ are produced

A

Disease susceptibily is depends on expression of certain classes of MHC II

  • only certain mouse strains are susceptible (DBA/1 most susceptible)
  • limits utility

Timing of disease onset and severity of disease can be variable

unlike RA patients Collagen antibodies are produced

42
Q

Mouse that have been genetically engineered to over-express human TNF (hTNF.Tg ) are quite good in the human-like onset and

A

blocking TNF will reduce/block disease severtity

Is dependent on the IL1 receptor expression and signalling

(used extensively

43
Q

What are the pros and cons of the hTNF.Tg mouse model?

A

Pros

reliable arthritis, chronic

useful to assess effect of TNF inhibition

Cons.

even though IL-1 is essential to arthritis it is a TNF driven model

Arthritis not dependent on T or B cells

44
Q

Process of inflammation and bone loss is similar with ___and ____ and ____ playing a dominant role

A

Process of inflammation and bone loss is similar with TNF and IL-1 and RANKL playing a dominant role

Molecule to Malady (36 decks)

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