Allergy II

Question 1

What kind of different eiologies and phenotypes can ashma have?

Answer 1

mild, moderate, severe
allergic and non allergic
esoniophilic or non-eosinohpilic
type 2-high or type 2- low

Question 2

What are features of type 2 asthma vs non-type 2 asthma?

Answer 2

more severe
ariway and systemic eosinophilia
responsiveness to steroids (non-tyype 2 non-responsive)
responsive to inhibtoros of type 2 inflammation

Question 3

If type 2 ashtma is eosinophilic, what is often seen with non-type 2 asthma?

Answer 3

neturophilic

Question 4

what immediate things are released in immediate allergic asthma?

Answer 4

tryptase, histamine, later is leukotrienes prostaglandins and cytokines.

Question 5

What cytokines can mast cells and T cells release?

Answer 5

type 2 cytokines, IL-3 IL-4, Il-5, Il-13.

Question 6

What products do eosinophils release?

Answer 6

peroxidase collagenase and toxic proteins.

Question 7

What cytokine recruits eosinophils?

Answer 7

Il-5.

Question 8

What do B2 agonists do?

Answer 8

Prevents bronchoconstriction.

Question 9

What cytokines, cell types and antibodies can steroids non specifically decrease?

Answer 9

decreases IL-4, IgE, eosinophils, basophils, mastcells CD4s CD8s (Th2 and Tc2)

Question 10

What cell type does steroids increase? What might this not be recommended for?

Answer 10

steroids increase neutrophil counts, not good for non-type 2 asthmas with neutrophilia.

Question 11

What are the receptors for leukotrienes.

Answer 11

CystLT1/2R,

found on many immune cells like lymphocytes basophils, macrophages mast cells, neutrophils, eosinophils.

Question 12

Although leukotriene modifiers can reduce Th2 cytokine production via leukotrienes and eosinophilia, why isn’t it very effective clinically on its own?

Answer 12

because pDG2 also released from mst cells which affect many cells as well.

Question 13

What are two mutations that cause hyper IgE syndromes?

Answer 13

STAT3 and DOCK8, eosinophilia and high IgE, eczema.

musculoskeletal, dental and facial abnormalities as well.

Question 14

What is Grazax?

Answer 14

tablet form of immunotherapy for grass allergy immunotherapy to grass pollen.

Question 15

What is alutard SQ?

Answer 15

subcutaneous allergy vaccination containing grass + tree
house dust mites and animal dander
Bee and wasp venom

Question 16

What beneficial responses are induced in response to allergy immunotherapy?

Answer 16

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.

Question 17

what kind of monoclonal is Omalizumab?

Answer 17

an anti-IgE ab.

Question 18

What kind of monoclonal is Mepolizumab and benralizumab?

Answer 18

an antib-IL5 and anti-Il5R (benralizumab) which reduce eosinophilia in asthma.

Question 19

What monoclonals are Dupilumab and Lebrikizumab?

Answer 19

anti- IL-4Ra and anti-IL-13 ab.

Question 20

What is the PDG2 receptor?

Answer 20

CRTH2 (or DP2)

Question 21

Why are innate-like lymphocytes difficult to identify? What markers can you use to identify them?

Answer 21

lineage- CD45hihg CD127+ CRTH2+

Question 22

two kinds of ILC3 populations are there?

Answer 22

LTIs- important for LN formatino and secrete LT-a and LTB

Others are ILC17s and produce Il-17.

Question 23

What alarmin cytokines do epithelial cells produce that can activate ILC2s?

Answer 23

IL-33, TSLP and IL-25.

Question 24

What other T cell cytokine can contribute to ot ILC2 activation?

Answer 24

PDG2 from T cells.

Question 25

What therapy options aim to inhibit ILC2s?

Answer 25

Those blocking the alarmins from epithelial cells Il-33 Il-25 and TSLP.

Question 26

Why might ILC2s be important in some cases of severe asthma?

Answer 26

ILC2s are very highly increased in severe asthma patients who are therapy resistant.
ILC2s are also steroid resistant.

Question 27

Apart from ILC2s, what other lymphocyte population is increased in severe eosinophilic asthma? What cytokines do they produce that benefits eosinophil survival and recruitment?

Answer 27

Tc2 cells (CD8+ CRTH2+)

Secrete IL-5 and GM-CSF

Question 28

How else might Tc2 cells (apart from Il-5 and GM-CSF) contribute to asthma?

Answer 28

Via PDG2 production and initiating airway remodelling via fibroblasts.