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Host Defense 2 > BoneFat > Flashcards

BoneFat Flashcards

1
Q

How do OB, OC and immune cells communicate?

A

RANK_RANKL system

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2
Q

What do OB release that promote OC survival and proliferation?

A

M-CSF

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3
Q

RANK is expressed on pre-OC and OC, what is the cytokine?

A

RANKL

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4
Q

What is a decoy receptor mainly from OB?

A

OPG

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5
Q

What ratio determines bone formation?

A

OPG and RANKL

-any condition that promotes OC dominance will be associated with bone pathology

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6
Q

Can lots of different things make RANKL? What can RANKL be expressed by?

A

yes

innate and adaptive immune cells, including neutrophils, monocytes, CD, T and B cells

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7
Q

What induces RANKL and promote OC?

A

Proinflammatory cytokines
1,6,8 TNF
17***

Dominant Th1 response in and around bone associated with INF-gamma and activated macrophages –>pro-clastogenic and bone resorption

Th17 POTENT OC activator
-Th1 or Th2 would inhibit 17—good thing

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8
Q

What inhibits RANKL?

A

Anti-inflmmatory cytokines like 4 and 10 inhibit OC

-sex hormones

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9
Q

What cytokine is high in bone remodeling in Rheumatoid arthritis? What does this lead to?

A

IL 23
–>Th 17 cells infiltrate the synovium
IL 17 activates neighboring OC and they proliferate
—>neutrophils
-RANK/RANKL/OPG balance is pro bone loss and causes bony erosions and loss of joint function

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10
Q

What does estrogen promote? What happen in the post menopausal state?

A

Promotes normal OB and OC function

Post menopausal state: OPG/RANKL balance is altered

  • high levels of RANKL causes not increase in OC activity
  • blocking RANKL with monoclonal antibody can lead to decreased bone loss
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11
Q

What is the largest endocrine organ?

A

adipose tissue

-any stimulus that increases inflammation in adipose tissue is a bad thing

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12
Q

What are the functions of white adipose tissue? WAT

A
  • super endocrine organ and critical for homeostasis
  • produces hormones, chemokines, and cytokines
  • regulates energy storage and expenditure, body mass and immune responses
  • composed of pre-adipocytes, adipocytes, stromal/vascular cells and macrophages
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13
Q

What are the two major types of WAT macrophages?

A

M1=proinflammatory

M2=anti-inflammatory

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14
Q

What are the macrophage cytokines in WAT?

A

osteopontin-pro-inflamamtory and potent chemotactic signal for monocytes and macrophages

Restin-antagonist of adiponectin( adiponectin is anti-inflamitory)

-Il 1,6,8 TNF alpha

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15
Q

What are the adipocytokines? What do they do?

A
  1. Leptin-proinflammatory cytokine
  2. Adiponectin-anti-inflammatory
  3. Macrophage inhibitory cytokine-is TNF-like but promotes adiponectin release
  4. Visfatin-pro-inflammatory and pro angiogenic
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16
Q

WHat is the normal WAT relationship between inflammatory and anti-inflammatory adipocytokines ?

A

slightly anti-inflammatory milieu

17
Q

What happens in obese WAT?

A

expanding fat in adipocytes triggers signals that make WAT very pro-inflammatory

  • recruits large number of monocytes and macrophages
  • portal vein carries the problem into the liver also into atheromatous plaques
18
Q

Adipose tissue is also around organs such as the heart what does this mean/

A

-inflammatory milieu has an effect

19
Q

What happens to the macrophages in obesity?

A

Being converted to M1 producing inflammatory cytokines and recruiting more monocytes that are then also converted to pro-inflammatory

20
Q

What is local obesity?

A

Fatty artery

  • cholesterol in the plaque attract M1 macrophages
  • Macrophages secrete CCL2 to attract monocytes and then prohibit them from exiting
  • Big plaque to ruptured plaque is clinical problem of huge dimensions –> myocardial infarction
21
Q

What is CCL2?

A

chemokine

-brings monocyte in and prevent them from leaving

22
Q

How are innate immune response held inactive in the brain?

A

supression by microglia and IL10 and TNF B

23
Q

WHat are the 2 subsets of microglia in the CNS?

A
  1. Act like M2 macrophages, highly branched, display little MHC, don’t want any innate response
    - secrete IL 10 and TGF B
  2. Perivascular-derived from circulating monocytes can sense what’s going on in the blood
    - can cause a lot of problems
24
Q

What happens when you get encephalitis?

A

glial system is activated by DAMPs and PAMPS (perivascular part)

  1. rapidly converts M2 to M1
    - now you have pro-inflammatory macrophages in the brain,
  2. unregulated MHC and change in morphology
  3. start producing 1,6,8 tnf alpha
    - 1,6= depression (even with just a flu)
25
Q

What are the clinical implications of neuroinflammation?

A

pro-inflammatory cytokines-especially IL6 have potent effects on neural function and survival
-may be important cause of delirium-long term traumatic brain damage

Host Defense 2 (12 decks)

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