Type 1 immunopath Flashcards
Hypersensitivity
excessive/damaging reaction produced by normal immune system
hypersensitivity reactions require __ state of the host
a pre-sensitized
Cellular component of hypersensitivity
main cell = mast cell/basophil
amplified by platelets, neutrophils, eosinophils
mechanism of hypersensitivity
production of IgE in response to allergens
why are some people allergic?
produce more Th2 cells that secrete IL-4, IL-5, IL-13 –> IgE class switch
IgE high affinity for Fce, CD23 receptor
Atopic
individuals with predisposition to certain allergic hypersensitivity reactions through life
Allergy/Allergen
Atypical response to enviorn antigen mediated by IgE and mast cell
Anaphylaxis
life-threatening type 1 rxn
Asthma
reversible bronchoconstrictive disease with progressive inflammation –> fibrosis
wheal and flare
develop hives after intradermal injection of allergen
Incidence of atopic disease in general popn
15%
incidence of atopic diseae with 1 allergic parent?
2 allergic parent?
35%
65%
Mechanism of IgE hypersensitivity
1) Th2-like Tfh –> B cells –> IgE
2) IgE binds mast cell/basophil IgE receptor (FceRI)
3) Mast cell releases granules when 2 IgE molec cross-linked by allergen
4) Degranulation –> release histamine, heparin, enzymes, TNF (15 min) (itch, redness, leakiness)
5) Mast cell converts membrane phospholipids –> PGs/LTs (ECF-A)
(ECF-A) ==> inflammation, bronchoconstriction, attract eosinophil (4-10hrs)
Common features of Atopic diseases
Abnormal IgE response to environ antigen
Mediated by Th2 cells
Why use glucocorticoid?
Treat inflammation caused by late-phase reactants/Th2 in lung
Prevents chronic inflamm/irrev fibrosis
Why glucocorticoids over steroids?
steroids not easily absorbed
more side effects
Procedure of intradermsal skin test
1) drop allergen on forearm
2) prick epidermis
3) diameter of wheel/flare
codeine = control (histamine-releaser)
Safety of intradermal skin test
dangerous for severe allergies
Specificity of intradermal skin test
many false positives due to cross reactions and subclinical sensitivities
Time of immediate vs. late phase
w/n 15 min vs. 4-10 hrs
Mediators of immediate allergic rxn
Histamine
Heparin
enzymes
TNF
Mediators of late phase rxn
PGs,
LTs
cytokines
Therapy: Avoidance
cornerstone of treatment
Therapy: antihistamines
early, acute symptoms
epinephrine
first line in emergencies
cromolyn sodium
stabilizes mast cell
limit histamine release
theophylline
incr cAMP, bronchial smooth muscle relaxation
glucocorticoids
block PG/LT synthesis
induce eosinophil apoptosis
leukotriene inhibitors
addition to asthma tx
IgE monoclonal antibody
mops up IgE in blood
immunotherapy
allergy shots with incr allergen concentration
Mechanism of IgG, IgE, M2 macrophage, eosinophil in helminth immunity
1) worms induce strong Th2
2) Th2 cells stim B cells to produce IgG/IgE
3) IgG binds worm/ova (attract neutrophils that can’t destroy worm)
4) antigens from worm diffuse to IgE that is bound to mast cell
5) IgE cross-linked by bound antigen and causes mast cells to degranulate
6. Released histamine causes peristalsis!
7. Mast cells are also activated to produce PGs and LTs that attract eosinophils!
8. eosinophil have receptor for IgG coating worm so bind receptor and release MBP that destroy worm
9) Th2 release lymphokines that attract and activ M2 macrophage
10) M2 macrophage heal damage/wall off worm
