Allergy II Flashcards
What kind of different eiologies and phenotypes can ashma have?
mild, moderate, severe
allergic and non allergic
esoniophilic or non-eosinohpilic
type 2-high or type 2- low
What are features of type 2 asthma vs non-type 2 asthma?
more severe
ariway and systemic eosinophilia
responsiveness to steroids (non-tyype 2 non-responsive)
responsive to inhibtoros of type 2 inflammation
If type 2 ashtma is eosinophilic, what is often seen with non-type 2 asthma?
neturophilic
what immediate things are released in immediate allergic asthma?
tryptase, histamine, later is leukotrienes prostaglandins and cytokines.
What cytokines can mast cells and T cells release?
type 2 cytokines, IL-3 IL-4, Il-5, Il-13.
What products do eosinophils release?
peroxidase collagenase and toxic proteins.
What cytokine recruits eosinophils?
Il-5.
What do B2 agonists do?
Prevents bronchoconstriction.
What cytokines, cell types and antibodies can steroids non specifically decrease?
decreases IL-4, IgE, eosinophils, basophils, mastcells CD4s CD8s (Th2 and Tc2)
What cell type does steroids increase? What might this not be recommended for?
steroids increase neutrophil counts, not good for non-type 2 asthmas with neutrophilia.
What are the receptors for leukotrienes.
CystLT1/2R,
found on many immune cells like lymphocytes basophils, macrophages mast cells, neutrophils, eosinophils.
Although leukotriene modifiers can reduce Th2 cytokine production via leukotrienes and eosinophilia, why isn’t it very effective clinically on its own?
because pDG2 also released from mst cells which affect many cells as well.
What are two mutations that cause hyper IgE syndromes?
STAT3 and DOCK8, eosinophilia and high IgE, eczema.
musculoskeletal, dental and facial abnormalities as well.
What is Grazax?
tablet form of immunotherapy for grass allergy immunotherapy to grass pollen.
What is alutard SQ?
subcutaneous allergy vaccination containing grass + tree
house dust mites and animal dander
Bee and wasp venom
What beneficial responses are induced in response to allergy immunotherapy?
Tregs producing Il-10 and TGF-B which inhibit Th2 responses.
Th1 responses also induced that stimulate IgG4 responses that compete for allergen with IgE.
what kind of monoclonal is Omalizumab?
an anti-IgE ab.
What kind of monoclonal is Mepolizumab and benralizumab?
an antib-IL5 and anti-Il5R (benralizumab) which reduce eosinophilia in asthma.
What monoclonals are Dupilumab and Lebrikizumab?
anti- IL-4Ra and anti-IL-13 ab.
What is the PDG2 receptor?
CRTH2 (or DP2)
Why are innate-like lymphocytes difficult to identify? What markers can you use to identify them?
lineage- CD45hihg CD127+ CRTH2+
two kinds of ILC3 populations are there?
LTIs- important for LN formatino and secrete LT-a and LTB
Others are ILC17s and produce Il-17.
What alarmin cytokines do epithelial cells produce that can activate ILC2s?
IL-33, TSLP and IL-25.
What other T cell cytokine can contribute to ot ILC2 activation?
PDG2 from T cells.
What therapy options aim to inhibit ILC2s?
Those blocking the alarmins from epithelial cells Il-33 Il-25 and TSLP.
Why might ILC2s be important in some cases of severe asthma?
ILC2s are very highly increased in severe asthma patients who are therapy resistant.
ILC2s are also steroid resistant.
Apart from ILC2s, what other lymphocyte population is increased in severe eosinophilic asthma? What cytokines do they produce that benefits eosinophil survival and recruitment?
Tc2 cells (CD8+ CRTH2+)
Secrete IL-5 and GM-CSF
How else might Tc2 cells (apart from Il-5 and GM-CSF) contribute to asthma?
Via PDG2 production and initiating airway remodelling via fibroblasts.
