IgE Mediated Lung Disease Flashcards
What is the second signal in the immunological synapse between a B-cell and a T-cell?
CD40 - CD40L
What are the helper B-cell cytokines?
IL4, IL5, IL13
What happens if the immunological synapse between a B-cell and T-cell is incomplete?
- B-cell dies
2. T-cell dies / becomes anergic
What makes antibodies?
Plasma cells (B-cells)
What is IgE produced in response to?
Parasitic infections
- patients with worms, bilharzia, malaria, etc. typically have high IgE levels
What is the aim of IgE?
To make an environment which is very hostile to the parasite.
After IgE binds to parasite what occurs next?
The Fc receptor binds to high affinity receptors on mast cells and basophils.
- both mast cells and basophils are long-lived and the Fc receptor is very sticky (tends to stay bound, almost impossible to remove without killing mast cell)
What is the lifespan of a memory B cell?
Extremely long, tend to be tenacious
How does linking of IgE take place?
After IgE is bound, there is potential for it to become cross-linked when it binds to a pathogen.
What is the result of IgE cross-linking?
Cross-linking results in basophil and mast cell degranulation.
What are the 2 ways in which activated basophils and mast cells act?
- Release pre-formed granules
2. Make new things
What do preformed granules contain?
- Histamine
- Heparin
- Proteases
- Cytokines - Th2 cytokines and pro-inflammatory mediators
- Serotonin
What do newly synthesized granules contain?
- Lipid mediators especially prostaglandins and leukotrienes (most important)
- Platelet activating agents
- Substance P
What is substance P?
P = pain
- pain stimulator
The effects of mast cell granules: what does histamine do?
- Binds to neuro-receptors = causes pain
- Causes smooth muscle contraction
- Increases vascular permeability
The effects of mast cell granules: what do the cytokines do?
- Pro-inflammatory e.g. TNF-alpha
2. Th2 e.g. IL-4, IL-5, IL-13 = stimulate B-cell differentiation and cause eosinophil proliferation
The effects of mast cell granules: what do the proteases do?
- Destroy tight junctions between endothelial cells to increase vascular permeability
- Break down collagen and other extra-cellular matrix proteins
The effects of mast cell granules: what do the lipid mediators do?
- Increased inflammation
2. Increased vascular permeability
What is a potent eosinophil growth factor?
IL-5
What specific chemokine do eosinophils respond to?
Eotaxin
Which cells recruit eosinophils?
Mast cells and basophils
What do eosinophils do once they have reached the correct place?
They begin to secrete a large number of proteins which are similar to those produced by mast cells and basophils.
- stay there and continue to degranulate
= chronic inflammation
(e.g. why bilharzia leads to bladder cancer)
What is the protective role of IgE?
Mice (and humans) which lack IgE cannot form an appropriate response against parasitic infections.
Mast cells and basophils mediate a response against which types of parasites?
Both internal and external parasites
What happens when there are no parasites?
There seems to be a tendency to produce IgE to non-noxious stimuli
- this is called the hygiene hypothesis
What is atopy?
The genetic predisposition to produce IgE
What is allergy?
The inappropriate immunological response to innocuous stimuli
e.g. house dust mite faeces, cockroach faeces, pollen
What are some of the factors which implicate IgE overproduction in asthma?
- Asthma is exacerbated by Th2 cytokines
- Eosinophils are found in high numbers in allergic lungs
- Eosinophils contribute to mucous production and bronchoconstriction in allergic asthma
- Basophils are found in the bronchial fluid of individuals who die of asthma (+ eosinophils)
- In mouse models, challenging the lung with parasites produces a syndrome similar to allergic asthma
What can be done for atopy?
Don’t know what causes atopy, we can however delay it or ameliorate it.
- get an animal for the child
- introduce allergens early (especially if breastfed)
What is more likely to happen the longer you have untreated asthma?
Leads to irreversible airway damage
Inflammation in COPD is mediated by what cells?
Neutrophils
Inflammation in asthma is mediated by what cells?
Eosinophils
What is the most important immune cell in asthma?
Th2 T-cell
What is the effect of asthma on mucous production?
Leads to increased mucous production
What are potentially the most important mediators of asthma?
Leukotrienes
How can aspirin lead to asthma?
Diverts the arachidonic acid pathway to asthma stimulating leukotriene production
What is Omalizumab?
An monoclonal antibody against IgE
Where has Omalizumab shown success?
It has been effective in the treatment of resistant severe asthma.
What special monitoring should patients on Omalizumab receive?
They should be monitored for parasitic infection
- dewormed every few months
Where does Omalizumab fit in the treatment protocols of asthma?
Not mainstay but ancillary treatment for severe asthma only
- not a cure because it has no effect on Th2 T-cell (vs. steroids that are very effective because they kill leukocytes)
