Allergy and Asthma II Flashcards
Describe the number of eosinophils seen as athsma and allergy compared to basal levels. What reduces eosinophil numbers?
- often elevated in asthma and allergy
- steroids (e..g prednisone, ICS) are extremely effective at reducing eosinophi counts in blood
Why did Jorda Duran think that eosinophils are a source of red blood cells?
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
Describe how eosinophils are differentiated in the bone marrow
puripontent stem cells –> mature to CFU-GEMM –> generate CFU-Eo progenitors –> GM-CSF, IL-3, IL-5 –> generate eosinophils
Describe the structure of the eosinophil crystalloid granule
- lipid bilayer membrane
- crystalline core - MBP, cytokines
- Matrix - EPX, ECP
What pathogen do eosinophils have a strong response to? What notion did this lead to? What’s a caveat with this notion?
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)
Why is it unlikely that eosinophils are exclsuively assoicated with conferring defence against parasitic infections?
eos appeared after multicellular parasites have appeared, making this unlikely
What happens to eos KO mice when they are infected with a virus (PVM)?
low eos –> mortality of host
high eos –> survival of host
What pathogenic agents do eosinophils defend against?
several helminthic parasites, some bacteria, fungi, and viruses
How many asthma patients have eosinophils present in lung tissue?
50%
In status asthmaticus, where are the eosinophils localized to in lung tissue?
infiltrate the subepithelial mucus
Describe eosiniphil extravasation
- tethering and rolling via E- and P-selectins, VCAM1
- flattening, integrin activation and adhesion via CCL5/RANTES, CCL11/CCL24
- diapedesis
- chemotaxis
- activation
- mediator release
How was the role of eosinophils in allergy and asthma thought of before and after 1990?
- before: eos considered anti-inflammatory and thought to be be bystander cells in asthma and allergy
- after: eos are pro-inflammatory in these diseases
What is the role of IL-5, what does it bind to?
- key cytokine for the maturation, activation, and survival of eos
- binds to IL-5R on eos
Describe the traditional mouse model of asthma, how is it induced? What immune cell levels are elevated in the BAL of these models?
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
How are asthma symptoms in OVA mice with and without eosinophils?
with - very high
without - normal