Lecture 21 - Mast Cells Flashcards Preview

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Flashcards in Lecture 21 - Mast Cells Deck (31):
1

Who discovered mast cells?

Paul Ehrlich

2

Name for state of elevated anti-allergen IgE levels

Atopic

3

Mast cell locations

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

4

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

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

5

How do mast cells interact with blood vessels?

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

6

Complement proteins that can activate mast cells

C3a, C5a

7

Neuropeptide that can activate mast cells

Substance P

8

Do mast cells release different factors based on different stimuli?

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

9

Piecemeal degranulation

'Kiss and run'.
Release of some of granule contents, but not all.

10

Type of degranulation triggered by IgE stimulation

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

11

Morphological changes in mast cells upon IgE stimulation

Ruffling of membrane. Cell can die.

12

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

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

13

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

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

14

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

1) Leukotrienes (particularly C4)
2) Prostaglandins (particularly D2)

15

Arachidonic acid pathways stimulated in mast cells

Those that result in the production of leukotrienes and prostaglandins

16

Potent arachidonic acid bronchocontrictor released by mast cells

Leukotriene C4

17

Mediators released by mast cells through transcriptional modulation

Cytokines and chemokines

18

FceRI structure

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

19

ITAM

Immunoreceptor tyrosine-based activation motifs

20

Mast cell stabilising drug

Disodium cromoglycate (DSCG)

21

Mice used to study role of mast cells

Mice with a mutation in the stem cell factor system.

22

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

Stem cell factor system is important for many cell types.

23

Way around problems with stem cell factor-deficient mice.

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

24

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

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

25

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

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

26

Way to selectively kill mast cells

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

27

Things that mast cells provide immunity against

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

28

Parasite-derived mast cell inhibitor

ES-62.
From filarial nematodes

29

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

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

30

Way to block IgE-dependent degranulation pathway in mast cells

Omalizumab (anti-IgE humanised MAb)

31

Mast cell-activating adjuvant

Compound 48/80.
Used in vaccines