Flashcards in IgE channels and allergies Deck (55)
What is an allergy?
Disease following an immune response to an allergen
What immunoglobulin is most associated with allergies?
What is a hypersensitivity reaction
Inappropriate or exaggerated immune response that causes inflammation, tissue damage and disease.
What is the end result of sensitization to an allergen
Production of allergen-specific IgE and up-regulattion of T helper cells
How are allergens sampled in the lungs
Dendritic cells sample in the airway lumen or tissue itself if the allergen has transferred through disrupted epithelium.
Where do dendritic cells migrate to and mature
Migrate to the regional lymph nodes or local mucosa, where they present allergen derived peptides on their MHCII complexes to naive T cells.
What is required to be present for maturation of naive T cells to T helper cells
IL-4 (enhanced by engagement of notch on the surface of T cells with Jagged on dendritic cells).
What is the result of T helper cell interaction with B cells
Cause them to mature into plasma cells and undergo immunoglobulin class-switch recombination
What is immunoglobulin class-switch recombination in the context of asthma
Plasma cells' gene segments encoding Ig heavy chains are rearranged so IgE antibodies are produced.
What do circulating IgE receptors bind to after reaching the interstitial fluid?
Allergen specific or non-specific IgE binds to the high affinity receptor for IgE on tissue resident mast cells. FcεRI
Does sensitisation produce any symptoms
Give an example of how the T helper cell response to allergens can be treated
IL-4 receptor dosage binds IL-4, inactivating naturally occurring IL-4 without cellular activation.
What needs to occur for an active response of a mast cell
Binding of two IgE antibodies by the antigen on the mast cells surface
What do mast cells do when activated
Release preformed mediators and increase the synthesis of many cytokines, growth factors and chemokines.
What is the result of mast cell activation
Bronchoconstriction, vasodilation, increased vascular permeability, increased mucous production
How does mast cell activation contribute to the late phase transition
Promoting the influx of inflammatory leukocytes: By upregulating adhesion molecules on vascular endothelial cells. But also by secreting chemotactic mediators, especially leukotriene B (LTB) and prostaglandin D2 (PGD2) and chemokines such as IL-8
What innate immune cells are present in the late phase reaction
Neutrophils, eosinophils, basophils, monocytes
What adaptive immune cells are present in the late phase reaction
Antigen stimulated T-cells.
What is the action of neutrophils in the late phase reaction
Release of elastase - promotes the activation of matrix metalloproteinases (MMPs) and the subsequent degredation of type III collagen
What is the action of eosinophils in the late phase reaction
Release basic proteins that can injure epithelial cells
What are other late phase reaction results
Bronchoconstriction, increased mucus production
What do B2-adrenoceptor agonists do
salbutamol, relax smooth muscle, inhibit mast cell degranulation and inhibit mucus secretion.
What do corticosteroids do
repress transcription of newly synthesised mediators like chemokines, other cytokines and prostanoids by the inhibition of COX2 induction.
What is the action of Omalizumab/ Zolair
IgE antibody - blocks IgE receptors from binding to mast cells.
Very costly, must be injected, and has no effect on mast cells that already have IgE associated with them.
What subunits make up the tetrameric FcεRI receptor
one alpha, one beta, two gamma
What regulates the synthesis of FcεRI
IL-4 produced by TH2cells
What is the importance of the FcεRI beta and gamma chains
They contain the ITAMs (immunoreceptor tyrosine based activation motif) - These are required for initiation of signalling
How to ITAMs induce signalling
Tyrosines in ITAMs are targets for phosphorylation by Src tyrosine kinases and subsequent SH2 domain binding of intracellular signalling molecules
What is the role of the beta subunit of the FcεRI
amplifies signalling and stabilises cell surface expression