Lecture 21 - Mast Cells: friend and foe Flashcards Preview

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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 ..

Allergic diseases

Elevated allergen-specific immunoglobin E levels - atopy

Allergic rhinitis


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

complement fragments


cytokines/chemokines/growth factors

bacterial componenets

physical trauma


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?

FceRI Receptor

which activates

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
b-cell receptor
T-cell receptor
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?

CV disease
kidney disease
Rheumatoid arthritis
CNS - multiple sclerosis
infectious diseases


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

certain parasites
certain bacteria
certain viruses

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

bacteria infection


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


What are the ways of utilising mast cell?

Enhance mast cell activation in immunity as a vaccine adjuvant

Compound 48/80 - mast cell stimulator given at the time of vaccine - get protection from death