Bone and Fat Immunology

Question 1

What is the OB precursor?

Answer 1

Osteochondral Precursors

Question 2

What is the OC precursor?

Answer 2

Monocytes

Question 3

What is M-CSF?

Answer 3

Macrophage colony stimulating factor and it is secreted by OBs and promotes differentiation of pre-OCs into OCs

Question 4

What is RANK?

Answer 4

It is present on OCs and is the target for RANKL

Question 5

What is RANKL?

Answer 5

Cytokine that directs OC differentiation and drives bone resorption

Question 6

What is OPG?

Answer 6

It is secreted by OB as a decoy receptor for RANKL and serves to block that activity of RANKL.

Question 7

What determines the loss or gain of bone?

Answer 7

Ration of RANKL to OPG

Question 8

What cytokines induce RANKL synthesis?

Answer 8

IL-6
IL-17
TNF-alpha
(pro-inflammatory)

Question 9

What cytokines inhibit OC formation?

Answer 9

IL-4
IL-10
(anti-inflammatory)

Question 10

What is the cause of rheumatoid arthritis?

Answer 10

Th17 reaction driven by inappropriate DC release of IL-23 which leads to uncontrolled OCs as IL-17 release will stimulate OB production of RANKL

Question 11

What is the cause of osteoporosis?

Answer 11

OPG/RANKL become imbalanced with RANKL dominating and OCs will increase

Question 12

What is an effective method of treating osteoporosis?

Answer 12

Monoclonal Ab to RANKL

Question 13

What is the function of leptin?

Answer 13

Decreases appetite and is pro-inflammatory

Question 14

What is the function of adiponectin?

Answer 14

Antagonist of leptin and is anti-inflammatory through the inhibition of TNF-alpha

Question 15

What is the function of MAC-1?

Answer 15

Macrophage inhibiting cytokine and it stimulates adiponectin.

Serum levels have a negative correlation with body mass

Question 16

What is the function of visfatin?

Answer 16

It is pro inflammatory and angiogenic in WAT

Question 17

What are the cytokines made by WAT?

Answer 17

Leptin
Adiponectin
MAC-1
Visfatin

Question 18

What are the cytokines made by macrophages in regulation of WAT?

Answer 18

Osteopontin

Resistin

Question 19

What is the function of osteopontin?

Answer 19

It is pro inflammatory and chemotactic for macrophages and monocytes

Question 20

What is the function of resistin?

Answer 20

Direct antagonist of adiponectin and promotes TNF-alpha and IL-6

Question 21

What is the normal cytokine state of WAT tissue in non-obese individuals?

Answer 21

The leptin and visfatin (pro inflammatory) and adiponectin and MAC-1 (anti-inflammatory) are in balance

Question 22

What is the macrophage state in normal individuals?

Answer 22

M2 - anti-inflammatory with with up regulation of IL-4/10 and attenuation of NFkB

Question 23

What is the cytokine state of WAT in obese individuals?

Answer 23

Loss of the balance due to the expansion of the WAT which leads to the release of CCL2 which is highly pro inflammatory

Question 24

What is the function of CCL2?

Answer 24

It binds to CCL2R which is a potent pro inflammatory stimulus

Question 25

What is the macrophage state in obese individuals?

Answer 25

M1 - pro inflammatory with increased visfatin/leptin/resistin which drain to the liver and cause hepatic and systemic effects

Question 26

What occurs with CCL2 and CCL2R deficiencies?

Answer 26

Leads to no formation of artery plaques in mice

Question 27

What are microglia?

Answer 27

They are the phagocytic cells of the CNS

Question 28

What are the 2 subsets of microglia?

Answer 28

- Migrated from marrow and are self renewing with macrophage/DC characteristics with a low concentration of MHC receptors - Perivascular and are derived from the marrow like plasma monocytes

Question 29

What is the state of the microglia?

Answer 29

They are all down regulated like the M2 macrophages and they make TGF-beta, IL-10 and IL-1Ra (receptor antagonist)

Question 30

What converts microglia to the activated state?

Answer 30

DAMP and PAMP converts the M2 to M1 and will result in the secretion of pro inflammatory cytokines