Flashcards in Lecture 21 - Mast Cells: friend and foe Deck (22):
The mast cell has dense granules packed full of ...
mediators that can do alot of harm and good
Mast cells are best known for their role in ..
Elevated allergen-specific immunoglobin E levels - atopy
Where are mast cells particularly located?
body sites in contact with the external envirnoment - skin/gut/lung
commonly found close to BVs/nerves/glands
What kind of stimuli can activate Mast cells?
Antigen - via IgE
Degranulation of mast cells happens how?
granules fusing with the cell membrane
What are the types of granulation?
peace-mule degranulation: fuse with the membrane, release and be reintegrated
Compound degranulation - one will fuse, and then lots with will fuse the first granule to form a large space of content release
What is in the granules?
other protease - kinase
There are some pre-formed cytokines, early stage inflammatory response
Arachidonic acid pathway triggers: Leukotrience C4 (LTC4) and PGD2
Transcriptional regulators to upregulate cytokine and chemokines genes (TNF-a) for long, sustained response
What is the mast cells activation receptor?
ITAMS - Immunireceptor Tyrosine-based Activation MotifS (have a consensus sequence)
What are the core elements of the FceRI Receptor signaling?
1. receptor crossing linking
2. draw together Src kinases, leads to phosporylation of ITAM motifs
3. Draws in other tyrosine kinases (Syk) - which has lots of downstream substrates
4. Adaptor proteins + second messengers (IP3) and Ca2+ which eventually leads to the process of degranulation
5. Activation of phospholipases and transcription factors
ITAM-mediated signalling is commonly found along with what inhibitory version?
ITIM - Immunoreceptor tyrosine-based inhibitory motif - ITIM
ITAM-mediated signalling is a common pathway in what...
Immune regulating receptors
Fc receptors for other immunoglobulins
What two ways have mast cells been examined?
Mast cell deficient mice - mutation in stem cell factor system:ligand, receptor, gene promotor
mast cell "stabilising' drug - Disodium cromoglycate (DSCG) - not known how it works, can also effect other cells
Mast cell deficient aniamls can be reconsituted with...
mast cells grown in culture
Mast cells will then repopulate the areas where they should go
So shows whether the phenotype is reversed with the mast cells are introduced
Other than Allegric disease, where else does mast cells do bad things?
CNS - multiple sclerosis
In Asthma how is mast cells bad?
mast cells uniquely elevated in asthmatic airways - found in close proximity to airway smooth muscle cells
Causes the 'twitchyness"
In Obesity how is mast cells bad?
increase amount in human white adipose tissue from obese donors - enhanced serum levels of tryptase
mast cell deficient animals gain less weight on western diet
Whats a way mast cells could be killed?
Fc2'3 - PE40
IgE - Fc portion binds to FceRI
Fused with Pseudomonas exotoxin A (PE40)
This toxin causes cell death
means of targeting and selectively eliminating mast cells
What situations are mast cells friendly?
Immunity to infection
but not just infection
UV skin damage
CNS - anxiey
Cancer - can reduce growth in some types of cancer
ES-62 is glycoportein secreted by some parasites that tries to..
dampen down the mast cell degranulation
Mast cell deficient animals have a very poor survival in a _____ ______ model
What are the ways of targeting mast cells
Anti-histamines (for hayfever etc..)
Omalizumab (humanised anti0IgE antibody) block the IgE-dependent activation pathway
Selective syk kinase inhibitors - block the IgE-dependent activation pathway