What are ITAMs?
immunoreceptor tyrosine-based activation motif. ITAMs are important for signal transduction in immune cells
What is IgE bound to on mast cells?
How is a mast cell activated?
IgE binds to allergen/pathogen Phosphroylation event Degranulation
3 Stages of histamine communication with environment?
Immediate, Rapid, Slow
Why is the histamine response in 3 distinct phases?
Immediate (Histamine, Heparine, Tryptase TNFa) - preformed granules are released due to phosphorylation (ITAMs) Rapid (Cyteinyl leukotrienes, PGD2) - delay is caused by the need to de-esterify the aceyl-lipid (using PLA2) Slow (IL-4, IL-5, GM-CSF) - delay is caused by the need to transcribe the genes. This response promotes the survival of Th2 cells and eosinaphils
What endogenous factors inhibit mast cell activation?
PGE2, adrenaline, cortisol
What is the role of cyteninyl-leukotrienes?
They are released only during inflammation (no other known physiological role). Bronchocontrictor Vasoactive Cause leaky vessels
Drug which prevents the formation of cysteinyl leukotrienes:
Montelukast - it is a CysLT1R antagonist - it is a good target as it has no other physiological role
What is type 1 hypersensitivity?
Immediate hypersensativity - it is mediated by mast cells,, IgE and lipid mediators
What is type 2 hypersensitivity?
Antibody mediated - IgM and IgG against cell bound or extracellular matrix antigen
What is type 3 hypersensitivity?
Immune complex - IgM and IgG immune complex deposition
What is type 4 hypersensitivity?
Delayed type - CD4 mediated delayed type hypersensitivity
What is atopy?
Allergic reaction assocaited with high levels of IgE, eosinophils and Th2 (which secrete IL-4)
Why do allergens stimulate an immune response?
Allergens induce Th2 - this is because of the way that they enter into the body - it is the same process as parasites
Describe the process of sensitization
What causes the differentiation of Th2 cells (from CD4 T cells)?
Describe the process of IgE production
Refer to diagram
What are the components of the immediate pahse?
Wheal and Flare
Wheal - localized swelling (vessel dilation and leakage)
Flare - redness and sensitization in the surrouding area
Late phase of hypersensativity?
Hard swelling - accumulation of leukocytes
What are H1 receptor antagonists used for?
To treat allergies (antihistamines)
What are the oldest H1 antagonists? Why aren't they used anymore?
H1 receptors are also associated with wakefulness these antagonists cause sedation which is sufficient to interfere with lifestlye
Newer (but not newest) H1 recpetor antagonsits?
Why aren't they used
Associated with sudden ventricular arrythmia
Newest non-sedative H1 antagonists
What are the H2 receptor antagonists used for? what are they called?
Inhibits the interaction between histamine and the H2 recepotr and thus inhibits the production of cAMP. The lack of cAMP thus fails to activate the K+/H+ channel thus preventing a releae of H+ and preventing a pH drop and an exacerbation of a peptic ulcer
How can mast cells be inhiited?
These drugs are humanised murine antibodies which find to FceR1 and thus prevent it from binding to IgE. It is administered subcutanously and prevents degranulation.