Lecture 21: Regional and System Specific Immunology Flashcards
What do osteoclasts differentiate from?
myeloid progenitors (monocytes)
What are the 2 fates of monocytes?
macrophages and osteoclasts
What 2 factors are ESSENTIAL for differentiation and maturation of macrophage/monocyte precursors into osteoclasts?
M-CSF and RANKL
What can bind and neutralize RANKL (thereby negatively regulating osteoclastogenesis)?
OPG
How do OBs, OCs, and immune cells communicate with each other?
RANK-RANKL system
What cells release M-CSF?
Osteoblasts
The ratio of _____ and ______ determines bone formation
OPG and RANKL
True or false: any condition that promotes OC dominance will be associated with bone pathology
true
What turns cells on?
RANKL (then osteoblasts can secrete M-CSF)
What effect does M-CSF have?
turns on pre-osteoblasts (to increase #)
Aside from osteoblasts, what else can secrete RANKL?
B and T lymphocytes
True or False: RANKL is expressed only by monocytes
FALSE - also neuts, DC, T and B cells
basically, they can all activate osteoclasts
Which cytokines promote osteoclasts and how do they do it?
IL-1, 6, 8, 17, and TNF
(the proinflammatory cytokines)
they induce RANKL (OPG cannot keep up)
Which cytokines inhibit OC?
4 and 10 (anti inflammatory ones)
What effect does Th1 response around bone have?
pro-clastogenic and bone resorption
OC activation
What effect does Th17 have on bone?
POTENT OC activator
on the flip side, a normal Th1 or 2 response wouldn’t be such a bad thing since it can block this
Which is more damaging to bone, Th1 or Th17?
Th17
What is a clinical example of unbalanced bone remodeling?
rheumatoid arthritis
What cytokine is elevated in the synovium of the joint in RA patients?
IL-23
Which cytokine of a Th17 response activates neighboring OC to proliferate?
IL-17
If B and T cells are the source of RANKL, how can RA be treated?
lots of monoclonal antibodies!
Why is bone loss a common problem in post menopausal women?
estrogen is a stimulator of OPG (blocks RANKL so OC isn’t stimulated)
What is a drug you can give to post menopausal women to prevent OC?
denosumab (an anti RANKL monoclonal)
