Bone and Fat Immunology Flashcards
What is the OB precursor?
Osteochondral Precursors
What is the OC precursor?
Monocytes
What is M-CSF?
Macrophage colony stimulating factor and it is secreted by OBs and promotes differentiation of pre-OCs into OCs
What is RANK?
It is present on OCs and is the target for RANKL
What is RANKL?
Cytokine that directs OC differentiation and drives bone resorption
What is OPG?
It is secreted by OB as a decoy receptor for RANKL and serves to block that activity of RANKL.
What determines the loss or gain of bone?
Ration of RANKL to OPG
What cytokines induce RANKL synthesis?
IL-6
IL-17
TNF-alpha
(pro-inflammatory)
What cytokines inhibit OC formation?
IL-4
IL-10
(anti-inflammatory)
What is the cause of rheumatoid arthritis?
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
What is the cause of osteoporosis?
OPG/RANKL become imbalanced with RANKL dominating and OCs will increase
What is an effective method of treating osteoporosis?
Monoclonal Ab to RANKL
What is the function of leptin?
Decreases appetite and is pro-inflammatory
What is the function of adiponectin?
Antagonist of leptin and is anti-inflammatory through the inhibition of TNF-alpha
What is the function of MAC-1?
Macrophage inhibiting cytokine and it stimulates adiponectin.
Serum levels have a negative correlation with body mass
What is the function of visfatin?
It is pro inflammatory and angiogenic in WAT
What are the cytokines made by WAT?
Leptin
Adiponectin
MAC-1
Visfatin
What are the cytokines made by macrophages in regulation of WAT?
Osteopontin
Resistin
What is the function of osteopontin?
It is pro inflammatory and chemotactic for macrophages and monocytes
What is the function of resistin?
Direct antagonist of adiponectin and promotes TNF-alpha and IL-6
What is the normal cytokine state of WAT tissue in non-obese individuals?
The leptin and visfatin (pro inflammatory) and adiponectin and MAC-1 (anti-inflammatory) are in balance
What is the macrophage state in normal individuals?
M2 - anti-inflammatory with with up regulation of IL-4/10 and attenuation of NFkB
What is the cytokine state of WAT in obese individuals?
Loss of the balance due to the expansion of the WAT which leads to the release of CCL2 which is highly pro inflammatory
What is the function of CCL2?
It binds to CCL2R which is a potent pro inflammatory stimulus
What is the macrophage state in obese individuals?
M1 - pro inflammatory with increased visfatin/leptin/resistin which drain to the liver and cause hepatic and systemic effects
What occurs with CCL2 and CCL2R deficiencies?
Leads to no formation of artery plaques in mice
What are microglia?
They are the phagocytic cells of the CNS
What are the 2 subsets of microglia?
- 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
What is the state of the microglia?
They are all down regulated like the M2 macrophages and they make TGF-beta, IL-10 and IL-1Ra (receptor antagonist)
What converts microglia to the activated state?
DAMP and PAMP converts the M2 to M1 and will result in the secretion of pro inflammatory cytokines
