L26: Bone & Fat

Question 1

Objectives?

Answer 1

 Explain how three cytokines regulate a balance between bone breakdown and formation.
 Understand how Th17 immune responses can perturb normal bone remodeling.
 Discuss the importance of adipose tissue cytokine systems and their control of
energy metabolism.
 Demonstrate the logic supporting attempts to manipulate adipocytokines to control obesity.
 describe the clinical implications of activating the innate immune functions of microglia in the brain

Question 2

Learning goal?

Answer 2

The student will be able to understand that not only is the immune system important for resistance to infection but regional immune systems have developed additional functions like maintenance of bone, control of energy homeostasis and protecting the brain from “collateral” damage.

Question 3

Decoy receptor for RANKL

Answer 3

OPG

Question 4

Ratio of what two factors determine bone formation

Answer 4

RANKL:OPG

Question 5

Any condition that promotes _______ dominance is associated with bone pathology

Answer 5

osteoclast

Question 6

Aside from OB, who else can secrete RANKL

Answer 6

T & B cells, DC, monocytes, neutrophils….

Question 7

What cytokine milieu induce RANKL and thus OC activity?

Answer 7

Proinflammatory cytokines 
IL 1
IL 6
IL 8
TNF-alpha
******IL 17 *****

Question 8

What cytokines inhibit OC activity

Answer 8

IL 4

IL 10

Question 9

Which of the following responses does NOT induce RANKL and bone remodeling?
A. Th1 response
B. Th2 response
C. Th17 response
D. TMMI response

Answer 9

B. Th2 response

inhibits Th17 response

Question 10

Rheumatoid arthritis synovium will express lots of what cytokine?

Answer 10

IL 23

Question 11

What inhibits Th17 response

Answer 11

Th2 response

Question 12

In Pannus, what cells are infiltrating?

Answer 12

Th17

Question 13

What are the 2 kinds of macrophages in WAT

Answer 13

M1 and M2

Question 14

Which WAT macrophage is pro-inflammatory? anti-inflammatory?

Answer 14

M1 is pro-inflammatory
M2 is anti-inflammatory

(1st year medical students are neurotic; 2nd year are more seasoned)

Question 15

Name 5 cytokines secreted by M1 macrophages

Answer 15

IL168
TNFalpha
Osteopontin
CCL2
Resistant antagonist adiponectin

Question 16

In addition to macrophages, WAT also has pro/anti-inflammatory adipocytes. Name 2 cytokines secreted by the pro-inflammatory adipocytes secrete!

Answer 16

Leptin

Visfatin (also pro-angiogenic)

Question 17

Name 2 cytokines secreted from anti-inflammatory adipocytes

Answer 17

Adiponectin

Macrophage inhibitory cytokine (promotes adiponectin release)

Question 18

Leptin. Pro-inflammatory or anti-inflammatory?

Answer 18

Pro

Question 19

Adiponectin. Pro-inflammatory or anti-inflammatory?

Answer 19

anti

Question 20

Macrophage inhibitory cytokine. Pro-inflammatory or anti-inflammatory?

Answer 20

anti

Question 21

visfatin. Pro-inflammatory or anti-inflammatory?

Answer 21

pro

Question 22

What promotes adiponectin release?

Answer 22

Macrophage inhibitory cytokine

Question 23

CCL2. Pro or anti-inflammatory?

Answer 23

pro

Question 24

Which chemokine is secreted from “local obesity” plaques

Answer 24

CCL2

Question 25

Normally, WAT should have a slightly ______ milieu

Answer 25

anti-inflammatory

Question 26

Name 2 types of microglia in brain

Answer 26

1. perivascular

2. early-migrating (DC/M2-like, highly branched)

Question 27

What cytokine promotes delirium?

Answer 27

IL-6