Flashcards in Lecture 21 - Mast Cells Deck (31):
Who discovered mast cells?
Name for state of elevated anti-allergen IgE levels
Mast cell locations
Particularly prevalent in sites in contact with outside environment (skin, GIT, lungs).
Often found near blood vessels, nerves, glands
Stimuli that activate mast cells
1) Antigen (via IgE conjugation)
2) Complement fragments
4) Cytokines, chemokines, growth factors
5) Bacterial components
6) Physical trauma
How do mast cells interact with blood vessels?
Can protrude into into lumen of blood vessel to sample contents of blood
Complement proteins that can activate mast cells
Neuropeptide that can activate mast cells
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
'Kiss and run'.
Release of some of granule contents, but not all.
Type of degranulation triggered by IgE stimulation
Several granules fuse together, release through one site on the cell membrane
Morphological changes in mast cells upon IgE stimulation
Ruffling of membrane. Cell can die.
Types of mediators released by mast cells
2) De novo synthesised
3) Transcriptional regulation
Granular mediators released by mast cells
3) Other proteases
4) Certain cytokines (EG: TNFa)
De novo synthesised mediators released by mast cells
1) Leukotrienes (particularly C4)
2) Prostaglandins (particularly D2)
Arachidonic acid pathways stimulated in mast cells
Those that result in the production of leukotrienes and prostaglandins
Potent arachidonic acid bronchocontrictor released by mast cells
Mediators released by mast cells through transcriptional modulation
Cytokines and chemokines
1) Binding site made of alpha1, alpha2 subunits. Alpha 2 is transmembrane
2) FceRbeta, FcRgamma are transmembrane, have ITAMAs
Immunoreceptor tyrosine-based activation motifs
Mast cell stabilising drug
Disodium cromoglycate (DSCG)
Mice used to study role of mast cells
Mice with a mutation in the stem cell factor system.
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.
Way around problems with stem cell factor-deficient mice.
Reconstitute mice with mast cells from another source. Look for differences in phenotype.
Things other than allergic disease that mast cells are implicated in
1) Cardiovascular disease
2) Kidney disease
3) Rheumatoid arthritis
How could mast cells be implicated in obesity?
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
Way to selectively kill mast cells
Conjugate pseudomonas exotoxin A (PE40) to an IgE Fc fragment.
Things that mast cells provide immunity against
Bacteria, viruses, parasites, envenomation, cancer, possibly anxiety.
Parasite-derived mast cell inhibitor
From filarial nematodes
Ways to block release of mast cell mediators
2) H1 receptor antagonists
3) Anti-IgE antibody (omalizumab)
4) Selective syk kinase inhibitors
Way to block IgE-dependent degranulation pathway in mast cells
Omalizumab (anti-IgE humanised MAb)