Lecture 21 - Mast Cells

Question 1

Who discovered mast cells?

Answer 1

Paul Ehrlich

Question 2

Name for state of elevated anti-allergen IgE levels

Answer 2

Atopic

Question 3

Mast cell locations

Answer 3

Particularly prevalent in sites in contact with outside environment (skin, GIT, lungs).
Often found near blood vessels, nerves, glands

Question 4

Stimuli that activate mast cells
1)
2)
3)
4)
5)

Answer 4

1) Antigen (via IgE conjugation)
2) Complement fragments
3) Neuropeptides
4) Cytokines, chemokines, growth factors
5) Bacterial components
6) Physical trauma

Question 5

How do mast cells interact with blood vessels?

Answer 5

Can protrude into into lumen of blood vessel to sample contents of blood

Question 6

Complement proteins that can activate mast cells

Answer 6

C3a, C5a

Question 7

Neuropeptide that can activate mast cells

Answer 7

Substance P

Question 8

Do mast cells release different factors based on different stimuli?

Answer 8

Yes. IgE stimulation results in release of all factors. Other stimuli result in piecemeal degranulation

Question 9

Piecemeal degranulation

Answer 9

‘Kiss and run’.

Release of some of granule contents, but not all.

Question 10

Type of degranulation triggered by IgE stimulation

Answer 10

Compound degranulation.

Several granules fuse together, release through one site on the cell membrane

Question 11

Morphological changes in mast cells upon IgE stimulation

Answer 11

Ruffling of membrane. Cell can die.

Question 12

Types of mediators released by mast cells
1)
2)
3)

Answer 12

1) Granular
2) De novo synthesised
3) Transcriptional regulation

Question 13

Granular mediators released by mast cells
1)
2)
3)
4)

Answer 13

1) Histamine
2) Tryptase/chymase
3) Other proteases
4) Certain cytokines (EG: TNFa)

Question 14

De novo synthesised mediators released by mast cells
1)
2)

Answer 14

1) Leukotrienes (particularly C4)

2) Prostaglandins (particularly D2)

Question 15

Arachidonic acid pathways stimulated in mast cells

Answer 15

Those that result in the production of leukotrienes and prostaglandins

Question 16

Potent arachidonic acid bronchocontrictor released by mast cells

Answer 16

Leukotriene C4

Question 17

Mediators released by mast cells through transcriptional modulation

Answer 17

Cytokines and chemokines

Question 18

FceRI structure

Answer 18

1) Binding site made of alpha1, alpha2 subunits. Alpha 2 is transmembrane
2) FceRbeta, FcRgamma are transmembrane, have ITAMAs

Question 19

ITAM

Answer 19

Immunoreceptor tyrosine-based activation motifs

Question 20

Mast cell stabilising drug

Answer 20

Disodium cromoglycate (DSCG)

Question 21

Mice used to study role of mast cells

Answer 21

Mice with a mutation in the stem cell factor system.

Question 22

Problem with mice with a deficiency in stem cell factor system as a model of mast cell deficiency

Answer 22

Stem cell factor system is important for many cell types.

Question 23

Way around problems with stem cell factor-deficient mice.

Answer 23

Reconstitute mice with mast cells from another source. Look for differences in phenotype.

Question 24

Things other than allergic disease that mast cells are implicated in
1)
2)
3)
4)
5)

Answer 24

1) Cardiovascular disease
2) Kidney disease
3) Rheumatoid arthritis
4) Obesity
5) MS

Question 25

How could mast cells be implicated in obesity? 1) 2) 3)

Answer 25

1) Elevated levels in human white adipose tissue in obese individuals. 2) Enhanced serum tryptase levels. 3) Mast cell-deficient animals gain less weight on western diet

Question 26

Way to selectively kill mast cells

Answer 26

Conjugate pseudomonas exotoxin A (PE40) to an IgE Fc fragment.

Question 27

Things that mast cells provide immunity against

Answer 27

Bacteria, viruses, parasites, envenomation, cancer, possibly anxiety.

Question 28

Parasite-derived mast cell inhibitor

Answer 28

ES-62. | From filarial nematodes

Question 29

``` Ways to block release of mast cell mediators 1) 2) 3) 4) ```

Answer 29

1) Anti-histamines 2) H1 receptor antagonists 3) Anti-IgE antibody (omalizumab) 4) Selective syk kinase inhibitors

Question 30

Way to block IgE-dependent degranulation pathway in mast cells

Answer 30

Omalizumab (anti-IgE humanised MAb)

Question 31

Mast cell-activating adjuvant

Answer 31

Compound 48/80. | Used in vaccines