Lecture 8.1: Cellular molecular aspects of Allergy

Question 1

True or false? Mast cells are present as resident inflammatory cells such as in skin, gut, lung, and promotes angiogenesis.

Answer 1

True.

Question 2

By what complex does allergen induced mast cell degranulation occur?

Answer 2

Cross linking of IgE with FceR1.

Question 3

True or false? FceR1 has intrinsic activity that can result in a clustering of domains known as ITAMS. ITAMS help to activate mast cells.

Answer 3

False. Although it is true that ITAMS help to activate mast cells.

Question 4

Briefly go through what happens after the binding of FceR1 with IgE.

Answer 4

ITAMS complex formed, results in phosphorylation of Lyn/syk, recruitment of tyrosine kinases.

Two steps can come from this: PLC phosphorylation leads to DAG -> PKC -> Degranulation. Or IP3 -> Ca -> degranulation.

MapK can also work together with PLC to produce arachidonic acid metabolites and cytokine gene transcription.

Question 5

What are the three responses of degranulation? Briefly go through each.

Answer 5

Immediate: Release of Histamine, heparin, tryptase, TNFa
Rapid: Release of cysteneiyl leukotrienes and PGD2.
Slow: Release of IL4-5, GM-CSF.

Question 6

Histamine acts on H1 and H2 receptors. What are their responses respectively?

Answer 6

H1: Bronchospasm, pain, itch, mucous secretion, vasodilation (hypotension), vascular permeability (hypovolemia).

H2: Activates SNSS, increasing HR, contractility.

Question 7

What enzyme produces cysteneiyl leukotrienes? By what cells?

Answer 7

Glutathione S-transferase. Macrophages, eosinophils, mast cells. Has no physiological roles. Can result in anaphylactic shock.

Question 8

What does montelukast do?

Answer 8

Blocks action of glutathione s-transferase.

Question 9

What is omalizumab?

Answer 9

Monoclonal antibody that binds to IgE, prevents binding to FceR1 receptors.