Asthma and Allergies Flashcards
What is a mast cell and where are they located?
Inflammatory secretory cell, particularly prevalent at areas exposed to the external environment and close to blood vessels, nerves and glands
What are some external and internal triggers of mast cells?
External
- drugs, allergens, stings, mechanical stimulation, uv light/heat, osmotic stimuli
Internal
- activated complement, neuropeptides
What is the triple response?
The redness, flare and wheal
Redness - vasodilation
Flare - sensory nerves spread the reaction, causing vasodilation in surrounding tissue
Wheal - exudation of fluid from tissues - localised swelling
How does sensitisation work?
First exposure to trigger –> allergen w/ APC –> CD4+ T cells activated, release IL-33 –> basophils –> release IL-4 –> Th2 response –> B cells produce IgE which binds to mast cells via FcER1
What happens on another exposure?
Allergen induced mast cell degranulation
- crosslinking of IgE bound FcER1, cellular tyrosine kinases recruited and activated –> PLC and MAPK leading to degranulation
What are the three phases of degranulation?
Immediate, rapid, slow
What happens in the immediate phase?
30-45 seconds, release of preformed mediators
- histamine, heparin, TNF-alpha, tryptase
What happens in the rapid phase?
10-30 minutes, release of cys-leukotrienes and PGD2
What happens in the slow phase?
Hours-days, release of cytokines eg IL-4 (IgE), IL-5 (eosinophil recruitment) and GM-CSF (macrophage activation)
What are the actions of histamine?
Pain and itch Bronchospasm Mucus secretion Vasodilation Vascular leak
What are the actions of LTC4?
Recruitment of eosinophils, mast cells and macrophages
Airway obstruction - Mucus, oedema, ASM shortening
Hypotension during anaphylactic shock - Vasodilator of skeletal muscles, hypovolaemia
Nasal obstruction - Mucus, oedema
What are the actions of LTB4?
Promotes inflammation by attracting leukocytes