Type 1 HSRs Flashcards
What is a type I HSR?
Immune reaction to innocuous/environmental antigen mediated by IgE induced degranulation
What are the 3 phases of type I HSRs?
- sensitization
- early phase
- late phase
What happens during the early phase of type I HSRs?
mast cell degranulation
IgE–FCERI
release of primary/secondary mediators
What happens during the late phase of type I HSRs?
cytokine production (IL-4, 5,13)
cellular recruitment (granulocytes and TH2)
What are 4 granulocytes?
- mast cells
- eosinophils
- neutrophils
- basophils
What receptor does IgE bind to with high affinity?
FCERI
What cytokine induces IgE class switching?
IL-4
What cytokine induces eosinophil recruitment?
IL-5
What cytokines signal to goblet cells?
IL-13
Where are mast cells located?
tissue
What is primary mediator?
histamine
What are 3 secondary mediators?
- prostaglandins
- leukotrienes
- TNF-a (anaphylaxis)
Degranulation induces PLA to produce ________ which makes __________ and _________
arachidonic acid
prostaglandins and leukotrienes
What pathway does leukotrienes use?
lipoxygenase
What pathway does prostaglandins use?
COX 2
What is the product of leukotriene synthesis?
cys LTR1
What is the product of prostaglandin synthesis?
DP1 and CRTH2
How does Singulair (Montelukast) reduce asthma symptoms?
cys-LTR1 antagonist (prevents leukotriene synthesis)
What does degranulation induce?
vasodilation
vascular permeability
smooth muscle contractions
mucus production
ROS/RNS
At high concentrations of NO its combined with ROS to form ____________
peroxynitrite
What 3 ways does peroxynitrite damage cells?
protein oxidation
apoptosis
necrosis
What cytokine induces the transition to the late phase response and why?
TNF-a
induces vascular permeability and adhesion molecules
What are some way the severity of the type I HSR can be affect?
- prior exposure
- concentration
- route of entry
- predisposition
What cytokine is important for anaphylaxis and why?
TNF-a
induces vascular permeability and adhesion molecules = now systemic
How does epinephrine inhibit anaphylaxis?
binds to alpha/beta adrenergic receptor which counter acts primary/secondary mediators
** improves cardiac output
How do steroids inhibit inflammation?
blocks pro-inflammatory NFkB signaling
What is the goal of SCITs?
divert the TH2 response
What 2 mechanisms do SCITs use to reduce allergies?
- induce Tregs (IL-10) and reduce TH2 (IL-4)
- switch IgE to IgG (FCGRIIB)
What is the inhibitory receptor on granulocytes used by IgG to prevent degranulation?
FCGRIIB
What does SHIP Phosphatase do in SCITs?
prevents IgE–Lyn phosphorylation –> degranulation
Beta-2 agonists target the same receptor as __________
epinephrine
How do anticholinergics reduce asthma symptoms?
allows acetylcholine to bind to M2 inhibitory receptor preventing ACs normal function of airway hyper-reactivity
What happens when eosinophils degranulate in the lungs in regards to M2 receptors?
MBP will bind to M2 so now acetylcholine cannot = no longer inhibitory = hyper-reactivity and bronchial spasms
Where are type I IL-4/13 receptors found?
lymphocytes
Where are type II IL-4/13 receptors found?
epithelial cells, goblet cells, smooth muscle cells, endothelial cells
What’s the difference between type I and II IL-4/13 receptors besides where they are located?
type I only binds IL-4
type II binds IL4- and IL-13
Atopic dermatitis is a IL-___ dominant disease
IL-13
Atopic dermatitis is a TH___ mediated response
TH2
What does atopic mean?
predisposition to allergic responses involving IgE
What is the atopic march?
AD development early in life commonly leads to food allergies –> asthma —> rhinitis
Asthma is IL-_____ dominant
IL-4
What is the genetic mutation in AD?
FLG gene
What does the FLG gene do?
crosslinks epidermal layer so its strong
FLG mutation is common in what race?
europeans and asians
What race has higher IL-17/TH17 levels in AD?
asians
FLG mutation is less common in _____________ but their AD is just as severe
african americans
What race has the highest IgE/Th2 response and a very low Th17/22 response?
african americans
Why is it important that AD is mediated differently in different races?
AD is not just mediated by TH2 but also TH17 due to polymorphisms
What is the polymorphism in AD regarding races?
(Q576R) IL-4 Ra gene mutatio
What are the 3 distinct features of AD?
epithelial barrier dysfunction
susceptibility to infections
atopic features (rhinitis and asthma)
What are 3 type I HSRs?
atopic dermatitis
asthma
allergies
