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PHAR 510 > Lecture 2 - Macrophages > Flashcards

Lecture 2 - Macrophages Flashcards

1
Q

describe the production of monocytes

A

created in bone marrow and regularly replenished

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2
Q

describe the fate of monocytes

A

can either remain as monocyte or become macrophages that survive longer

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3
Q

how are neutrophils and macrophages different?

A

macrophages are transcriptionally active and can activate/deactivate transcriptional program

neutrophils are already packed with everything they need

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4
Q

difference in production of monocytes vs tissue-resident macrophages

A

monocytes: constantly produced, replication relies on bone marrow

tissue-resident macrophages: made during embryogenesis and stay there, can self-replicate without bone marrow

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5
Q

progenitor of tissue-resident macrophage

A

embryo-myeloid progenitor

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6
Q

progenitor of monocyte

A

hematopoietic stem cell

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7
Q

why is the liver an important immune site?

A

all blood is filtered thru the liver –> can removal pathogens for ex. so requires some immune function

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8
Q

what is the hepatic portal vein? describe the blood

A

brings blood to the liver –> blood contains toxins, bacterial components, etc.

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9
Q

what are the 4 types of macrophages in the liver? which is tissue-resident?

A
  1. Kupffer cells (tissue-resident)
  2. Monocyte-derived liver macrophages
  3. Capsular macrophages
  4. Peritoneal macrophages
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10
Q

what is the main difference btwn the liver macrophages?

A

each have diff markers

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11
Q

marker on Kupffer cells vs alveolar macrophage

A

Kupffer cells express F4/80 but macrophages do not

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12
Q

what type of cells were Kupffer cells initially thought to be?

A

initially thought to be endothelial cells

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13
Q

where are kupffer cells located?

A

at sinusoids near the blood

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14
Q

what do Kupffer cells do? (3)

A
  1. clear bacteria, viruses, dead cells, etc. from the blood stream
  2. present antigen to T cell
  3. communicate with NK cells
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15
Q

when do Kupffer cells communicate with NK cells? (2)

A
  1. clearing Borellia infections (lyme disease)
  2. healing wounds
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16
Q

where are capsular liver macrophages found?

A

in the hepatic capsule, at the surface of the liver

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17
Q

what do capsular liver macrophages express?

A

MHC II

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18
Q

what type of cells were capsular liver macrophages initially thought to be?

A

initially thought to be DCs

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19
Q

what is the peritoneum?

A

smooth muscle membrane that lines the abdominal cavity and surrounds abdominal organs to protect the organs

20
Q

what is the peritoneal cavity?

A

between the organs and peritoneum

21
Q

what type of macrophages are in the peritoneal cavity?

A

cavity macrophages

22
Q

are cavity macrophages tissue-resident?

A

no

23
Q

what is believed to be the initial role of peritoneal cavity macrophages?

A

to help with healing internal trauma in the abdominal area

24
Q

besides peritoneal macrophages, what are 2 other examples of cavity macrophages?

A
  1. macrophages in pleural cavity btwn lung and ribcage
  2. macrophages in pericardium cavity around the heart
25
Q

what differentiates cavity macrophages from non-cavity macrophages?

A

all express GATA6

26
Q

why is surgery bad for cavity macrophages?

A

cavity macrophages are self-renewing so when surgery disrupts the cavity, the macrophages are gone and may never come back

27
Q

difference btwn bacteremia and sepsis?

A

bacteremia = bacteria in bloodstream, can lead to sepsis

sepsis = immune system overreacts to an infection and attacks normal tissues and organs

28
Q

why are Kupffer cells helpful in the context of bacteremia?

A

Kupffer cells can catch the infection and filter out the bacteria from the blood

29
Q

what type of people does bacteremia usually occur in?

A

mainly immunocompromised people

30
Q

what is the only way that harmful things can be removed from the lungs after they bypass the mucociliary system?

A

alveolar macrophages

31
Q

number of alveoli vs number of alveolar macrophages

A

alveoli > alveolar macrophages

32
Q

where are alveolar macrophages produced?

A

in fetal liver

33
Q

describe the number of alveolar macrophages over time

A

when born, many macrophages are placed into the alveolar space and as you breathe/over time, the number decreases so there are only a few alveolar macrophages

34
Q

are alveolar macrophages sessile? how do we know?

A

not sessile –> they move around

found by intravital microscopy

35
Q

what is found in the lung interstitial space?

A

interstitial macrophages

36
Q

describe production of interstitial macrophages and why they are unique

A

interstitial macrophages are derived from the bone marrow and replenished from monocytes in the lungs

UNIQUE: the only tissue-resident macrophages that are monocyte-derived

37
Q

what does mycobacterium tuberculosis cause? why is it unique?

A

causes tuberculosis

UNIQUE: one of the only respiratory, intracellular pathogens

38
Q

how does M. tb cause disease?

A

grows inside of alveolar macrophages –> alveolar macrophages are required to cause disease

39
Q

describe latency of M. tb and how it becomes active

A

since it is intracellular pathogen, it can be latent as an inactive pathogen

uses immune system (i.e. alveolar macrophages) to cloak itself for a long time

BUT when there is disease that shuts down immune system, alveolar macrophages break down and release M. tb

40
Q

what is the principle of adoptive transfers?

A

to understand how activated/deficient/abnormal immune cell will react in normal environment

41
Q

how does adoptive transfer work?

A

In mouse 1: CD4 or CD8 cells become activated and antigen-specific

In mouse 2: this mouse receives the cells to see how the T cells react to antigen in a diff mouse

42
Q

describe bone marrow chimera

A

irradiate mouse to kill bone marrow cells and give donor bone marrow –> to know if specific gene is important in immune cells vs other cells

43
Q

what is the purpose of bone marrow chimera to study TLRs?

A

TLRs are expressed in hematopoietic AND non-hematopoietic cells –> can’t just make KO bc will be deleted in all cells, so can KO in one mouse and then give its bone marrow to another mouse

44
Q

example of bone marrow chimera experiment for TLRs

A

TLR4 KO mouse: give radiation so no longer has immune cells, including TLR KO cells

inject WT mouse bone marrow

now the TLR4 KO mouse has TLR4 KO in all cells except immune cells will be TLR4 WT

if TLR4 KO mouse has phenotype in infection, the TLR4 plays a role in defending against infection

45
Q

can we use bone marrow chimera to look at tissue resident macrophages?

A

no

46
Q

what is the purpose of parabiosis?

A

to understand if circulating cells have an effect

47
Q

how does parabiosis work?

A

1 mouse has fluorescently labelled cells, 1 mouse does not –> now can see how fluorescent immune cells affect the other mouse in infection

can look at if young mouse can heal old mouse for ex.

PHAR 510 (11 decks)

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