Chapter 20 - Allergy Flashcards
what do allergic responses result from?
what are immune responses driven by? how are they carried? what activity do they contain?
harmful immune responses
non-infections Ags carried in particles, have protease activity
what kind of groups comprise allergens?
proteins and glycoproteins
what 2 ways do allergens activate the innate immune response?
intrinsic enzymatic activity
activation of PRRs
indoor allergens are associated with?
outdoor allergens?
asthma
allergic rhinitis
what are the sources of airborne proteins or glycoproteins?
tree and grass pollen
mold spores
animal dander
dust mite or cockroach secretions
what are 2 forms of dominant source allergens?
timothy grass pollen (UK)
birch pollen (Sweden)
what influences the development of atopy?
genetic factors (polymorphisms)
environmental factors (sensitization, # siblings, hygiene, vacc)
what effects Th2-mediated allergic inflammation?
Defects in target organs (skin, gut, bronchi)
Triggers (viral infections, allergen exposure, smoke, pollutants)
what are some factors favoring Th1 protective immunity?
TB, older siblings, day care exposure, farm life
What are some factors favoring Th2 phenotype leading to allergic diseases?
antibiotic use, diet, sensitization to dust mites, urban (thug) life
what is the risk of passing on atopic trait if both parents are atopic?
1 parent?
0 parents
75%
50
15
polymorphisms in what genes are known to cause atopy?
Beta chain of FcERIBeta
IL-4 gene
HLA-DR alleles
CD14
what is CD14, what does a polymorphism in it promote?
part of receptor for LPS
hypersensitivity
patients with ragweed pollen allergy have IgE and IgG hypersensitivity due to what allelic association?
HLA-DR2
what does high levels of IgE in the cord blood of infants predict?
future development of atopy
what is the main postulate of the hygiene hypothesis?
the increased incidence of allergy is associated with the decrease in exposure to common infections during early life
how can atopic (Th2) phenotype be prevented?
Th1 type response
what can limit the development of unrelated allergen-mediated disease?
increased # of Tregs
Anaphylaxis is what type of hypersensitivity?
what Ags and what effectors does it display?
what kind of damage is it associated with?
Type I, Ag: insect venoms, drugs, food
Effectors: IgE on basophils and mast cells
oedema, bronchoconstriction, vascular collapse, death
What is the major cytokine needed for Mast cells?
Basophils?
Eosinophils?
Stem cell factor and IL-3
IL-3
IL-5
Is the expression of FcERI high or low on mast cells?
basophils?
eosinophils?
high
high
low
what are the major granule contents of mast cells?
histamine, heparin/chondroitin sulfate, proteases
what are the major granule contents of basophils?
histamine, chondroitin sulfate, protease
what are the major granule contents of eosinophils?
Major basic protein, cationic protein, peroxidases, hydrolases, lysophospholipase
which chain of the FcERI receptor is responsible for IgE binding to activate mast cells?
which chain mediates signal transduction?
alpha
beta and gamma
Where are Abs always bound to due to the high affinity of the receptor?
receptors expressed on the cell surface
Biogenic amines (ie histamine) and lipid mediators (PGD2, LTC4) of activate mast cells induce what?
what type of response is this?
vasodilation, vascular leak, bronchioconstriction and intestinal hypermotility
immediate
cytokines (TNF) and lipid mediators (PAF, PGD2, LTC) contribute to what?
enzymes to what?
what type of response is this?
inflammation
tissue damage
late-phase reaction
what picks up allergens before migrating to LN?
what happens next and what are they presented to?
DC
allergens processed and presented to MHC class II
where are mast cells found?
basophils?
in tissue
in circulation
what does crosslinking of FcERI lead to ?
act. of cells and release of inflammatory mediators (amines, lipid mediators, chemokines and cytokines)
What are preformed mast cell-derived mediators?
histamine, TNF-alpha
What are granule associated mast cell-derived mediators?
Tryptase, chymase, peroxidase
What are formed during degranulation mast cell-derived mediators?
LTC4, PGD2, bradykinin, PAF
What are generated after transcritption mast cell-derived mediators?
IL-1, 2, 3, 4, 5, 6, GM-CSF, TNF-alpha
what contributes to early allergic reaction?
Late?
preformed, granule associated, bradykinin
LTC4, PGD2, PAF, generate after transcriptors (ILs)
what is essential for protection against noxious compounds, such as snake/scorpion toxins present in venoms?
mast cell proteases
how do mast cell proteases contribute to the inflammatory response?
degrading tight junction/hemidesmosomes, or inducing cytokine maturation
what cytokine contributes substantially to the pro-inflammatory response?
TNF
TNF-alpha and IL-1 have what target? what effect?
endothelial cells
inflammation
what effect does PGE2 have?
pain and vascular permeability
what effects does bradykinin have?
vasodilator, SM contraction, vascular permeability
what effects does histamine have?
what has the same effects as this?
SM contraction and vascular permeability
PGD2 and Leukotrienes
what is atopy?
how is it demonstrated?
the propensity for developing immediate hypersensitivity reactions to common environmental allergens
by skin prick test
what causes chronic disease development?
activation of Th2 lymphocytes and macrophages
recruitment and degranulation of eosinophils
obstruction and increase in airway responsiveness
progression inflammation toward airway remodeling
what are some things that happen in airway tissue remodeling?
activation of tissue fibroblasts, INC production of collagen and deposition
INC production of mucous by Goblet cells
SM hyperplasia and hypertrophy
INC acute obstruction of airflow
what are 3 characteristics of COPD?
disrupted alveolar attachments
mucous hypersecretion
mucosal and peribronchial inflammation and fibrosis
In desensitization the presence of IgE in the blood shifts away from IgE to what?
IgG
what are the 3 mechanisms of desensitization?
IgG blocking Abs (IgG4 competes with IgE for allergen binding)
Regulation (repeated exposure induces Tregs which invoke normal res)
Immune deviation (shift away from Th2 to Th1 CD4 cells results in cytokines, ie. IFN-Gamma which are inhibitory to IgE production)
