Allergy Flashcards
What are xenobiotics?
a chemical substance found within an organism that is not naturally produced or expected to be present within the organism.
What is the difference between intolerance and allergy?
intolerance
- affects the digestive system
= enzyme deficiency where the substance cannot be broken down
allergy
- affects the immune system
What are the stages of allergic reaction?
sensitisation/induction phase
- is the learning phase which has no symptoms
elicitation phase/challenge reaction
- immune response effector phase
= leads to systemic reaction
the dose-response relationships for each are different
What is the wheal and flare reaction?
wheal and flare is the body’s response to allergens
- is dependent on IgE and mast cells
= IgE binds to mast cells and upon encountering/binding to allergen antigen, it crosslinks and causes the degranulation of the mast cell thereby release of stored granules
= vascular smooth muscle response (dilation and leak)
is followed by a late phase consisting of the accumulation of leukocytes
- neutrophils, basophils, eosinophils and Th2 cells
What can mast cells release upon degranulation and what is their effect?
biogenic amines
- histamine = vasodilation
lipid mediators
- LTC4 (leukotrienes) = bronchoconstriction
- PGD2
cytokines
- TNF
enzymes
- tryptase
What is the difference between allergen response and bacterial response? What is released?
allergen response
- eosinophils, mast cells, basophils, Th2 cells, IgE antibody and cytokines (IL-4, IL-5 and IL-13)
bacterial response
- neutrophils, macrophages, Th1 cells, IgG antibody and cytokines (IFN-gamma and TNF-alpha)
What is the mechanism of action of Th2 cells during allergic reaction?
first exposure to allergen
activation of Th2 cells and stimulation of IgE class switching in B cells
- Th2 cells makes B cells produce plasma cells which make IgE instead of IgG
production of IgE
binding of IgE to Fc receptors on mast cells
- only mast cells, basophils and eosinophils bind to IgE
repeated exposure allergen
activation of mast cells and release of mediators
- immediate hypersensitivity
- late phase reaction
What occurs during the sensitisation and late phase of allergic reactions?
sensitisation
- activation of allergen specific Th2 cells and IgE synthesis
= antigen receptors specific for the allergen bind, internalise, process and present the antigen in MHC II
= antigen-MHC II complex is recognised by CD4+ Th2 cells which induce class switching of antigen specific B cells and secretion of IL-4
late phase
- allergens bind to dendritic cells, monocytes and B cells
= causes uptake of allergen and presentation of allergen derived peptides to CD4 Th cells
= this drives the late phase reactions which involve accumulation of inflammatory leukocytes (eosinophils, basophils, Th2 cells)
What is the function of IL-4 and Il-13?
are responsible for the switching of IgG and subsequent production of IgE
- IgE binds to high affinity receptors on mast cells, eosinophils and basophils
What is the hygiene hypothesis?
hygiene hypothesis suggests that early childhood infections provide a Th1 stimulus for the Th2 skewed immune system of humans
- prevent pro-allergic Th2 responses to becoming dominant
reduction in Th1 stimulus means that the immune system lacks this Th1 stimulus and continues to maintain a Th2 bias
- results in increased risk of allergy and asthma due to increased susceptibility to Th2 reactions
What type of reaction occurs in worm infections (helminths, worms and parasites)?
a Th2 biased immune response
- results in increased Th2 levels and subsequent IgE production but there is no allergic reaction
What are the advantages of chronic worm infections?
parasites elicit high levels of non-specific IgE
- no allergic reaction, target worms and parasites
saturates Fc receptors and reduces type I hypersensitivity
- reduced mast cell degranulation and release of mediators
associated with high levels of IL-10
- involved in reduction of allergic response
IL induced T regulatory cells
Why is it that someone who is allergic to cats in general, is not allergic to their own cat?
these people are found to produce IgG4 antibody responses without any IgE antibody
- IgG4 does not bind to mast cells, eosinophils or basophils therefore does not elicit an allergic reaction
= have a modified Th2 response which allows for tolerance to allergens
What are the three main points of therapeutic intervention proposed for treatment of allergic disease?
block initiation of the immune response by preventing development of disease promoting Th2 cells
- by intervention in early life
block activation of allergen specific Th2 cells either directly or indirectly through effects on antigen presenting cells
- by treatment with anti-inflammatories such as glucocorticoids or by allergen immunotherapy
block effector molecules that cause the clinical symptoms of allergic disease
- by treatment with antihistamines, leukotriene antagonists or neutralising antibodies specific for Th2 cytokines or IgE
What is specific immunotherapy (SIT)?
administration of increasing doses of extracts of allergens
- to induce tolerance
= results in an increased Th1:Th2 ratio and increased serum IgG
occurs in two phases
- dose escalation then maintenance
induces epitope specific T cell tolerance
increases IL-10 production by T cells and APCs
reduces Th2 cells and eosinophils at the sites of allergens
