Lecture 2 - Macrophages

Question 1

describe the production of monocytes

Answer 1

created in bone marrow and regularly replenished

Question 2

describe the fate of monocytes

Answer 2

can either remain as monocyte or become macrophages that survive longer

Question 3

how are neutrophils and macrophages different?

Answer 3

macrophages are transcriptionally active and can activate/deactivate transcriptional program

neutrophils are already packed with everything they need

Question 4

difference in production of monocytes vs tissue-resident macrophages

Answer 4

monocytes: constantly produced, replication relies on bone marrow

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

Question 5

progenitor of tissue-resident macrophage

Answer 5

embryo-myeloid progenitor

Question 6

progenitor of monocyte

Answer 6

hematopoietic stem cell

Question 7

why is the liver an important immune site?

Answer 7

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

Question 8

what is the hepatic portal vein? describe the blood

Answer 8

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

Question 9

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

Answer 9

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

Question 10

what is the main difference btwn the liver macrophages?

Answer 10

each have diff markers

Question 11

marker on Kupffer cells vs alveolar macrophage

Answer 11

Kupffer cells express F4/80 but macrophages do not

Question 12

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

Answer 12

initially thought to be endothelial cells

Question 13

where are kupffer cells located?

Answer 13

at sinusoids near the blood

Question 14

what do Kupffer cells do? (3)

Answer 14

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

Question 15

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

Answer 15

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

Question 16

where are capsular liver macrophages found?

Answer 16

in the hepatic capsule, at the surface of the liver

Question 17

what do capsular liver macrophages express?

Answer 17

MHC II

Question 18

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

Answer 18

initially thought to be DCs

Question 19

what is the peritoneum?

Answer 19

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

Question 20

what is the peritoneal cavity?

Answer 20

between the organs and peritoneum

Question 21

what type of macrophages are in the peritoneal cavity?

Answer 21

cavity macrophages

Question 22

are cavity macrophages tissue-resident?

Answer 22

no

Question 23

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

Answer 23

to help with healing internal trauma in the abdominal area

Question 24

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

Answer 24

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

Question 25

what differentiates cavity macrophages from non-cavity macrophages?

Answer 25

all express GATA6

Question 26

why is surgery bad for cavity macrophages?

Answer 26

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

Question 27

difference btwn bacteremia and sepsis?

Answer 27

bacteremia = bacteria in bloodstream, can lead to sepsis sepsis = immune system overreacts to an infection and attacks normal tissues and organs

Question 28

why are Kupffer cells helpful in the context of bacteremia?

Answer 28

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

Question 29

what type of people does bacteremia usually occur in?

Answer 29

mainly immunocompromised people

Question 30

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

Answer 30

alveolar macrophages

Question 31

number of alveoli vs number of alveolar macrophages

Answer 31

alveoli > alveolar macrophages

Question 32

where are alveolar macrophages produced?

Answer 32

in fetal liver

Question 33

describe the number of alveolar macrophages over time

Answer 33

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

Question 34

are alveolar macrophages sessile? how do we know?

Answer 34

not sessile --> they move around found by intravital microscopy

Question 35

what is found in the lung interstitial space?

Answer 35

interstitial macrophages

Question 36

describe production of interstitial macrophages and why they are unique

Answer 36

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

Question 37

what does mycobacterium tuberculosis cause? why is it unique?

Answer 37

causes tuberculosis UNIQUE: one of the only respiratory, intracellular pathogens

Question 38

how does M. tb cause disease?

Answer 38

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

Question 39

describe latency of M. tb and how it becomes active

Answer 39

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

Question 40

what is the principle of adoptive transfers?

Answer 40

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

Question 41

how does adoptive transfer work?

Answer 41

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

Question 42

describe bone marrow chimera

Answer 42

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

Question 43

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

Answer 43

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

Question 44

example of bone marrow chimera experiment for TLRs

Answer 44

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

Question 45

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

Answer 45

no

Question 46

what is the purpose of parabiosis?

Answer 46

to understand if circulating cells have an effect

Question 47

how does parabiosis work?

Answer 47

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.