Chapt. 6: Allergen-specific Immunotherapy Flashcards
What is the mechanism of action for SIT?
Induces allergen-specific regulatory T-cells that decrease T-cell responses to allergens. Over time, there is immune deviation from a predominantly TH2 to a predominantly TH1 pattern of cytokine production.
Offers a way to desensitize the patient, rendering them less sensitive to inhalation of seasonal or perennial allergens.
SIT
How long is the build-up phase of SIT?
7-12 weeks
How long are the monthly maintenance injections for SIT?
3 years
What are the 3 main indications for SIT?
Allergic rhinitis
Allergic asthma
Anaphylaxis due to allergy to wasp and bee venom
Risk factor for adverse reaction to SIT?
Unstable asthma
Treatment of choice for patients with systemic reactions to hymenoptera venom?
SIT
How to give SIT for patients with seasonal allergic rhinitis?
SIT given preseasonally for 3 years, but sometimes SIT is given all year round, again for a total of 3 years.
Improvement with SIT can be seen in what percentage of patients?
80%. Symptoms are reduced rather than abolished.
In the SIT for HDM, most clinicians would agree that if there is no benefit after ______ months, the treatment is unlikely to become effective on continuing SIT?
6 months
Are recognized causes of life-threatening episodes and epidemic outbreaks of asthma.
Airborne fungal spores
What are the main effectors of the allergic response?
Eosinophils
Basophils
Mast cells
What are reduced by SIT?
The increased levels of eosinophils seen during natural allergen exposure. There is also blunting of the seasonal increases in nasal basophils and mast cells
What increases after SIT?
Allergen-specific IgG4. This is generally considered to be a direct consequence of the injection of foreign material rather than the mechanism by which SIT works. Immediate cause of IgG4 production is induction of regulatory T cells producing IL-10.
SIT induces what allergen-specific regulatory T-cells, which produce which 2 key cytokines?
IL-10 and TGF-B
What is suppressed during SIT?
Suppression of allergen-specific lymphocyte proliferation and decreased production of interferon-gamma, IL-5, IL-13.
Is a general inhibitor of proliferative and cytokine responses in T cells, which inhibits IgE production and enhances IgG4 production?
IL-10
What is considered a marker of successful SIT?
Increased allergen-specific IL-10
TH2 cells preferentially secrete?
IL-4
TH4 cells preferentially secrete?
IFN-gamma
SIT leads to a _______ in allergen-specific TH2 cells, and an _______ in induction of cells producing IL-12.
Decrease, increase
Promotes Th1 lymphocyte proliferation and suppresses Th2 cells.
IL-12.
SIT should only be offered to patients with asthma in what conditions?
If their asthma is under control and their FEV1 is greater than the 70% predicted.
What is the maintenance dose of allergens for SIT?
6-20 ug of major allergen to achieve clinical efficacy.
What is the SIT schedule?
Consists of 2 phases: the build-up phase going from very low dose to the full maintenance dose, and then a maintenance phase, in which the same dose is given at intervals over a number of years.
What is the interval of the build-up phase?
Injections twice-weekly, weekly, or alternate weeks
Once patients reach the maintenance dose of their immunotherapy extract, what is the schedule of their injections?
Less frequent, every 4 weeks
How long does it take for severe reactions to manifest after SIT?
Within 20minutes of the injection, and a minimum observation period of 30minutes after injections is widely accepted as appropriate.
Can SIT be started during pregnancy?
Current advice is that it should not be started, but maintenance treatment may be continued, provided there is no history of systemic reactions.
_____ of patients do not complete their SIT courses.
10-46%
What are the standardized extracts available for SLIT?
HDM (Dermatophagoides farinae and pteronyssinus), cat dander, weeds (ragweed, Parietaria, mugwort), grasses, and tree pollens.
SLIT doses are _______ times those used in SCIT.
50-110x
Are local side effects common in SLIT?
Local effects are common, but systemic effects are rare.
How long duration of SLIT is recommended?
3 years or more
What is the mechanism of action of SLIT?
The fraction that is retained in the oral mucosa is taken up by the dentritic cells that migrate to regional lymph nodes.
How long do allergens persist in the mouth?
up to 20 hours after SLIT
What are the immunologic changes associated with successful SLIT?
Enhanced suppressor activity of IL-10 secreting regulatory T Cells (Tr cells), suppression of eosinophils, mast cells and basophils, and antibody isotype switching from IgE to IgG4.
Blocks the Th2 response and decreases the activation of mast cells and eosinophils?
TGF-b1
What is a consistent finding in most SLIT studies using large dose of allergen?
Induction of allergen-specific IgG4
What are the mechanisms of SLIT? (7)
Induction of IgG (blocking) antibodies
Reduction in specific IgE (long term)
Reduced recruitment of effector cells
Altered helper T cell cytokine balance (shift from Th1 to Th2)
T cell anergy
B cell suppression
Increased regulatory T cell (Treg) function.
Percentage reduction in symptom score and rescue medication use in patients with seasonal allergic rhinitis after SLIT?
30-40% reduction
SLIT appears to reduce asthma symptoms and medication scores after _____ years of treatment.
2 years
Rate of serious systemic side effects of SCIT in patients with rhinitis?
1 in 500 injections
What are the local side effects of SLIT?
Itching of the mouth and palate
What is the overall frequency of systemic adverse reactions to SLIT?
1 in 3000 doses
What is another potential mode of administration for SIT?
Intralymphatic route
Percentage reduction in symptom score and rescue medication use in patients with seasonal allergic rhinitis after SLIT?
30-40% reduction
SLIT appears to reduce asthma symptoms and medication scores after _____ years of treatment.
2 years
Rate of serious systemic side effects of SCIT in patients with rhinitis?
1 in 500 injections
What are the local side effects of SLIT?
Itching of the mouth and palate
What is the overall frequency of systemic adverse reactions to SLIT?
1 in 3000 doses
What is another potential mode of administration for SIT?
Intralymphatic route
