Allergy and Asthma II Flashcards

1
Q

Describe the number of eosinophils seen as athsma and allergy compared to basal levels. What reduces eosinophil numbers?

A
  • often elevated in asthma and allergy
  • steroids (e..g prednisone, ICS) are extremely effective at reducing eosinophi counts in blood
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2
Q

Why did Jorda Duran think that eosinophils are a source of red blood cells?

A

In llamas RBCs are elongated, and granules in eosinophils also appeared elongates, so it was interpreted that the function of eosinophils is as a precursor of RBCs

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3
Q

Describe how eosinophils are differentiated in the bone marrow

A

puripontent stem cells –> mature to CFU-GEMM –> generate CFU-Eo progenitors –> GM-CSF, IL-3, IL-5 –> generate eosinophils

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4
Q

Describe the structure of the eosinophil crystalloid granule

A
  • lipid bilayer membrane
  • crystalline core - MBP, cytokines
  • Matrix - EPX, ECP
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5
Q

What pathogen do eosinophils have a strong response to? What notion did this lead to? What’s a caveat with this notion?

A

strong response to helminthic parasites –> persistant notion that the main immunological role of eosiniophils is in combating helminithic parasites (caveat: only recognize IgE coated helminths, not directly)

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6
Q

Why is it unlikely that eosinophils are exclsuively assoicated with conferring defence against parasitic infections?

A

eos appeared after multicellular parasites have appeared, making this unlikely

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7
Q

What happens to eos KO mice when they are infected with a virus (PVM)?

A

low eos –> mortality of host
high eos –> survival of host

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8
Q

What pathogenic agents do eosinophils defend against?

A

several helminthic parasites, some bacteria, fungi, and viruses

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9
Q

How many asthma patients have eosinophils present in lung tissue?

A

50%

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10
Q

In status asthmaticus, where are the eosinophils localized to in lung tissue?

A

infiltrate the subepithelial mucus

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11
Q

Describe eosiniphil extravasation

A
  1. tethering and rolling via E- and P-selectins, VCAM1
  2. flattening, integrin activation and adhesion via CCL5/RANTES, CCL11/CCL24
  3. diapedesis
  4. chemotaxis
  5. activation
  6. mediator release
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12
Q

How was the role of eosinophils in allergy and asthma thought of before and after 1990?

A
  • before: eos considered anti-inflammatory and thought to be be bystander cells in asthma and allergy
  • after: eos are pro-inflammatory in these diseases
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13
Q

What is the role of IL-5, what does it bind to?

A
  • key cytokine for the maturation, activation, and survival of eos
  • binds to IL-5R on eos
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14
Q

Describe the traditional mouse model of asthma, how is it induced? What immune cell levels are elevated in the BAL of these models?

A

OVA model:
OVA + alum on day 0 and 14 (sensitization phase, trains B cells to produce IgE that mast cells will use) –> OVA challenge on day 24, 25, 26 –> assess pathology on day 28

eos are mostly present

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15
Q

How are asthma symptoms in OVA mice with and without eosinophils?

A

with - very high
without - normal

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16
Q

What is the function of methacholine?

A

triggers airway closure

17
Q

What cells activate eosinophils?

A

Th2 and ILC2

18
Q

Name two anti-IL5 therapies, include medication names

A
  • anti-IL5 - mepolizumab, reslizumab
  • anti-IL5R - benralizumab
19
Q

How does anti-IL5Ra work?

A

benralizumab binds to IL-5Ra –> Fc portion binds to FcgRIII on NK cells –> ADCC –> macrophages efferyctose apoptotic eosinophils

20
Q

What is the therapy course for asthma?

A

track 1:
1. ICS (inhaled corticosteroids)
2. anti-IL5, -IL5R, -TSLP

track 2:
1. take SABA and ICS
2. anti-IL5, -IL5R, -TSLP

21
Q

What is a caveat of anti-IL5?

A

only deplete BM progenitors and circulating eos, and are less effective against fully mature tissue eos

22
Q

What is a caveat and strength of anti-IL5R?

A

IL-5R is shed from eos as they enter tissue, but anti-IL5R effectively targets residual IL-5R experession on tissue eos because of its very high affinity, may not reach some tissue-resident eos (homeostatic eos)

23
Q

In what tissues does benralizumab and mepolizumab/reslizumb work in?

A

benralizumab - tissue, blood, BM
mepo/res - blood and BM

24
Q

Describe the specificity anti-IL5R has with eosinophils

A

depletes inflammatory eos, not resident eos