Local immunomodulation for treatment of asthma Flashcards
What is the difference between eosinophilic asthma and non-eosinophilic asthma?
Th2 predominant asthma’s have a eosinophilic phenotype whereas non-Th2 asthma’s have a non-eosinophilic phenotype. Eosinophilic asthma is more early onset and non-eosinophilic asthma is more late onset.
How does allergic sensitization take place?
Allergen is picked up and presented by DCs to Th0 cells, which develop to Th2 under stimulation from (among others) IL-4 cytokines. The Th2 produce IL-13, IL-4, and IL-5 and provide help to B-cells that undergo IgE class switching.
What happens on second encounter with allergens?
The IgE antibodies will bind Fc receptors on mast cells and cross-link allergens which will lead to degranulation with secretion of histamine, cytokines and prostaglandins leading to vasodilation and edema. In the long term this also leads to tissue damage and remodelling and airway hyperresponsiveness.
The production of IL-5 by Th2 cells will lead to activation of eosinophils that also produce cytokines and leukotrienes which contribute to the typical allergic inflammation symptoms.
Another effect is smooth muscle cell proliferation and a effect on epithelial barrier.
What happens in patients with asthma in reation to allergens, pathogens and other irritants?
In patients with asthma the epithelial layer will start to produce innate cytokines (IL-25, TSLP, IL-8, IL-33) in reaction to allergens, pathogens and other irritants. These innate cytokines have an effect on immune cells including ILC2, which amplify the allergic inflammation. There are also macrophages and DCs promoting a Th1 response which will lead to Th17 and neutrophil actvation (mostly late onset asthma).
What is the effect of omaluzimab?
It is a monoclonal anti-IgE antibody that neutralizes free IgE in the serum and so prevents binding of the IgE to Fc receptors and activation of mast cells.
Therapeutic Anti-IgE does not crosslink with IgE bound with Fc receptors.
When are Biologicals like Omalizumab given to patients?
Biologicals are only applied to a small group of severe (uncontrolled) asthma. Mostly only adults. Because these asthma’s are hard to control with other treatment.
What is Strachan’s hygiene hypothesis?
younger siblings have less hay fever because they are exposed to germs from older siblings.
