Lecture 21: Regional and System Specific Immunology

Question 1

What do osteoclasts differentiate from?

Answer 1

myeloid progenitors (monocytes)

Question 2

What are the 2 fates of monocytes?

Answer 2

macrophages and osteoclasts

Question 3

What 2 factors are ESSENTIAL for differentiation and maturation of macrophage/monocyte precursors into osteoclasts?

Answer 3

M-CSF and RANKL

Question 4

What can bind and neutralize RANKL (thereby negatively regulating osteoclastogenesis)?

Answer 4

OPG

Question 5

How do OBs, OCs, and immune cells communicate with each other?

Answer 5

RANK-RANKL system

Question 6

What cells release M-CSF?

Answer 6

Osteoblasts

Question 7

The ratio of _____ and ______ determines bone formation

Answer 7

OPG and RANKL

Question 8

True or false: any condition that promotes OC dominance will be associated with bone pathology

Answer 8

true

Question 9

What turns cells on?

Answer 9

RANKL (then osteoblasts can secrete M-CSF)

Question 10

What effect does M-CSF have?

Answer 10

turns on pre-osteoblasts (to increase #)

Question 11

Aside from osteoblasts, what else can secrete RANKL?

Answer 11

B and T lymphocytes

Question 12

True or False: RANKL is expressed only by monocytes

Answer 12

FALSE - also neuts, DC, T and B cells

basically, they can all activate osteoclasts

Question 13

Which cytokines promote osteoclasts and how do they do it?

Answer 13

IL-1, 6, 8, 17, and TNF
(the proinflammatory cytokines)

they induce RANKL (OPG cannot keep up)

Question 14

Which cytokines inhibit OC?

Answer 14

4 and 10 (anti inflammatory ones)

Question 15

What effect does Th1 response around bone have?

Answer 15

pro-clastogenic and bone resorption

OC activation

Question 16

What effect does Th17 have on bone?

Answer 16

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

Question 17

Which is more damaging to bone, Th1 or Th17?

Answer 17

Th17

Question 18

What is a clinical example of unbalanced bone remodeling?

Answer 18

rheumatoid arthritis

Question 19

What cytokine is elevated in the synovium of the joint in RA patients?

Answer 19

IL-23

Question 20

Which cytokine of a Th17 response activates neighboring OC to proliferate?

Answer 20

IL-17

Question 21

If B and T cells are the source of RANKL, how can RA be treated?

Answer 21

lots of monoclonal antibodies!

Question 22

Why is bone loss a common problem in post menopausal women?

Answer 22

estrogen is a stimulator of OPG (blocks RANKL so OC isn’t stimulated)

Question 23

What is a drug you can give to post menopausal women to prevent OC?

Answer 23

denosumab (an anti RANKL monoclonal)