MSI Allergy Flashcards
Type 1 HS reaction (aka immediate reaction) involves ___- mediated release of antibodies against the soluble antigen. This results in MAST CELL DEGRANULATION and release of ________ and other inflammatory mediators.
IgE, histamine
What type of hypersensitivity reaction causes allergic rhinitis, ocular allergic conjunctivitis, eczema, asthma, and anaphylaxis?
Type 1 hypersensitivity reaction (IgE mediated)
Which type of allergic reaction has SYSTEMIC EFFECTS and is a life-threatening emergency?
Anaphylaxis- Type 1 HS reaction- IgE mediated
Hygiene hypothesis: Early exposure to a diverse range of microorganisms and antigens may lead to overall ________ rates of allergies, asthma, and other immune disorders.
decreased
Delayed mediators in the process of allergic reactions
Leukotrienes
Leukotrienes are produced from arachidonic acid (via enzymes 5-Lipoxygenase and phospholipase A2) and have similar effects to…
histamine
Mast cell activation converts membrane phospholipids into arachadonic acid via which enzyme?
phospholipase A2
What substance, released from mast cells, stimulates bronchoconstriction, vascular permeability, eosinophil recruitment, and neutrophil recruitment?
Leukotrienes
What substance, released from mast cells, plays a role in tissue remodeling, cellular recruitment, vascular permeability, and acute allergic disease?
proteases
A clinical test for Type 1 (IgE) HS reactions to a variety of antigens injected or placed into small cuts in the skin produces what type of reaction?
“Wheal and flare”
Activated T cell release of IL-5, IL-3, and GM-CSF promotes which type of allergic reaction? (Immediate or late?)
Late reaction- eosinophils migrate through the bloodstream to target tissue.
Activated T cell release of IL-4 and IL-13 leads to which type of allergic reaction? (Immediate or late?)
Immediate- Membrane binding IgE activates B cells, which then activate mast cells. The activation of mast cells causes degranulation and the release of histamine and leukotrienes.
People with ______ ________ are four times more likely to suffer from asthma, eczema, and food allergies
allergic rhinitis
Biopsy of airways of patient with chronic asthma shows inflammatory infiltrate and airway changes known as __________ (thickened basement membrane and smooth muscle hyperplasia).
re-modelling
Most patients with chronic asthma are sensitised to a variety of ________ allergens.
airborne
Early phase of allergic reaction are based on the activation of _____ cells, which release mediators and cytokines
mast
What type of cells take up allergen for processing and presentation to MHC class II molecules in the late phase allergic reaction?
neutrophils
In the late phase allergic reaction, there is tissue redness and swelling d/t the arrival of cells to the area such as neutrophils, eosinophils, and lymphocytes (particularly ____ and ____ cells)
CD4 T cell, mast
Late phase allergic reactions develop within _______ hours of exposure to the allergen
6-12
CD4 subset ___
Cytokine: IFN-gamma, IL-12
Transcription factor: T-bet
Cytokines: IFN- gamma, lymphotoxin
Major functions: Anti-viral and mycobacterial effects, activation of macrophages to kill intracellular pathogens
Th1
** CD4 subset ____ **
Cytokine: IL-4
Transcription factor: GATA-3
Cytokines: IL-4, IL-5, IL-13
Major functions: Antiparasitic responses. Stimulation of IgE and other Ab production, increases mucous production, promotes eosinophilia
Th2
CD4 subset ____
Cytokine: IL-6, TGF-Beta1, IL-1 Beta
Transcription factor: ROR gamma t
Cytokines & mediators produced: IL-17A, IL-17F, IL-22
Major functions: Antibacterial and anti-fungal effects, recruitment and activation of PMNs
Th17
CD4 subset ______
Cytokine: TGF-Beta 1, IL-10
Transcription factor: FOXp3
Cytokines: TGF-Beta 1, IL-10
Major functions: Suppression of T cell activation, inhibition of APC function
Treg
___ cells are central players in immunity to helminths and are implicated in mediating the inflammatory pathology associated with allergies
Th2
Biopsies of allergic inflammation are rich in T cells expressing ___ cytokines
Th2
This Th2 mediator recruits mast cells
IL-9
This Th2 mediator is required for eosinophil survival
IL-5
These Th2 mediators promote mucus hypersecretion
IL-4 and IL-13
This Th2 mediator is required for B cell class switching to IgE
IL-4
The ___ hypothesis/model suggests a true role for T cells in chronic inflammation rather than just in causing IgE production- activated Th2 cells and other inflammatory cell accumulate, produce products that lead to disease
Th2
The World Allergy Organisation estimates of allergy prevalence of the whole population by country ranges between __-__%
10-40%
What is the most common chronic disease in Europe?
Allergies
Up to __% of patients with allergies live with a severely debilitating form of their condition, and struggle daily with the fear of a possible asthma attack, anaphylactic shock, or even death from an allergic reaction
20
__% of British adults now suffer from at least one allergy. Almost half of sufferers have more than one allergy.
44
The % of children diagnosed with allergic _____ and ________ have both trebled over the last 30 years.
rhinitis, eczema
Childhood allergy is strongly predicted by the presence of allergy in _________
parents
Low hygiene levels, high pathogen load, helminth infection proposed to skew immunity from ___ to ___ and induce regulatory T cells
Th2 to Th1
High hygiene levels, low pathogen load, and absence of helminth infection is proposed to skew immunity towards ___ cells and reduce production of regulatory T cells
Th2
Detection of allergen-specific IgE can be tested in vivo by using what type of testing?
What is a positive response?
Skin prick testing
A wheal and flare response after 15 minutes is positive
Laboratory diagnosis of allergies uses ________ testing- Detection of allergen-specific IgE in vitro (immobilised IgE Abs detected with polyclonal anti-IgE detection Ab).
ELISA
NB: ELISA testing has replaced RAST testing
Symptom relief in the treatment of allergies are nasal decongestants (act on alpha 1 adrenoreceptors to cause vasoconstriction), _________ (Beta 2 agonists promote smooth muscle relaxation), and epinephrine to oppose vasodilation and bronchoconstriction
salbutamol
The two easiest and most helpful allergy drugs for early-phase mediators are antihistamines (H1 receptor) and ___________ receptor antagonists
Leukotriene
First line medication to reduce the signs & sx of allergies is H1 antihistamines (MOA: _________ agonists at H1 histamine receptor). Best used before exposure to allergen.
inverse
Hydroxyzine onset of action? ______ hours
20
Leukotriene receptor antagonists (Montelukast) is effective in reducing early allergic responses, but inferior to H1 anti-histamines. Montelukast is beneficial in treating chronic ______ which is the main indication for its use.
asthma
______ reduce immune activation by altering gene expression in numerous cell types, including T cells, B cells, and cells of the innate immune system. Their onset of action is delayed and they must be taken regularly.
Steroids
Route of administration for beclametasone (for use in allergies)
Inhaled, nasal spray
Route of administration for hydrocortisone (for use in allergies)
Topical - skin
MOA of ___________:
Binds to glucocorticoid receptor leading to downstream effects such as:
Inhibition of phospholipase A2
Inhibition of Nuclear Factor-kappa B
Inhibition of other inflammatory transcription factors
Promotion of anti-inflammatory genes
hydrocortisone
____________ is a recombinant, fully human IgG1 monoclonal Ab subcutaneously administered biological disease modifier which targets Tumour Necrosis Factor (TNF).
Produced by recombinant DNA technology in a mammalian cell expression system and is purified by a process that includes specific viral inactivation and removal steps.
Adalimumab
MOA of _____________ is primarily linked to the neutralization of TNF-alpha bioactivity by preventing the interaction of TNF alpha with the cell surface of TNF receptors.
It inhibits several TNF-alpha induced events (eg the release of serum cytokines [IL-6], acute phase reactants of inflammation, matrix metalloproteases, and other markers of cartilage and synovium turnover, and the expression of adhesion molecules responsible for leukocyte migration.
Also, it lyses TNF-expressing cells in the presence of complement.
Adalimumab
Allergen-specific immunotherapy:
Allergen doses administered subcut or sublingually
Mainly used for venom allergy and rhinitis
Multiple immunological effects: Induce regulatory T cell responses to allergens Reduce \_\_\_ responses Induce allergen-specific IgG Abs Reduction in mast cell responsiveness Reduce allergen-specific IgE levels
Th2
