Chapt. 6: Allergen-specific Immunotherapy

Question 1

What is the mechanism of action for SIT?

Answer 1

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.

Question 2

Offers a way to desensitize the patient, rendering them less sensitive to inhalation of seasonal or perennial allergens.

Answer 2

SIT

Question 3

How long is the build-up phase of SIT?

Answer 3

7-12 weeks

Question 4

How long are the monthly maintenance injections for SIT?

Answer 4

3 years

Question 5

What are the 3 main indications for SIT?

Answer 5

Allergic rhinitis
Allergic asthma
Anaphylaxis due to allergy to wasp and bee venom

Question 6

Risk factor for adverse reaction to SIT?

Answer 6

Unstable asthma

Question 7

Treatment of choice for patients with systemic reactions to hymenoptera venom?

Answer 7

SIT

Question 8

How to give SIT for patients with seasonal allergic rhinitis?

Answer 8

SIT given preseasonally for 3 years, but sometimes SIT is given all year round, again for a total of 3 years.

Question 9

Improvement with SIT can be seen in what percentage of patients?

Answer 9

80%. Symptoms are reduced rather than abolished.

Question 10

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?

Answer 10

6 months

Question 11

Are recognized causes of life-threatening episodes and epidemic outbreaks of asthma.

Answer 11

Airborne fungal spores

Question 12

What are the main effectors of the allergic response?

Answer 12

Eosinophils
Basophils
Mast cells

Question 13

What are reduced by SIT?

Answer 13

The increased levels of eosinophils seen during natural allergen exposure. There is also blunting of the seasonal increases in nasal basophils and mast cells

Question 14

What increases after SIT?

Answer 14

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.

Question 15

SIT induces what allergen-specific regulatory T-cells, which produce which 2 key cytokines?

Answer 15

IL-10 and TGF-B

Question 16

What is suppressed during SIT?

Answer 16

Suppression of allergen-specific lymphocyte proliferation and decreased production of interferon-gamma, IL-5, IL-13.

Question 17

Is a general inhibitor of proliferative and cytokine responses in T cells, which inhibits IgE production and enhances IgG4 production?

Answer 17

IL-10

Question 18

What is considered a marker of successful SIT?

Answer 18

Increased allergen-specific IL-10

Question 19

TH2 cells preferentially secrete?

Answer 19

IL-4

Question 20

TH4 cells preferentially secrete?

Answer 20

IFN-gamma

Question 21

SIT leads to a _______ in allergen-specific TH2 cells, and an _______ in induction of cells producing IL-12.

Answer 21

Decrease, increase

Question 22

Promotes Th1 lymphocyte proliferation and suppresses Th2 cells.

Answer 22

IL-12.

Question 23

SIT should only be offered to patients with asthma in what conditions?

Answer 23

If their asthma is under control and their FEV1 is greater than the 70% predicted.

Question 24

What is the maintenance dose of allergens for SIT?

Answer 24

6-20 ug of major allergen to achieve clinical efficacy.

Question 25

What is the SIT schedule?

Answer 25

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.

Question 26

What is the interval of the build-up phase?

Answer 26

Injections twice-weekly, weekly, or alternate weeks

Question 27

Once patients reach the maintenance dose of their immunotherapy extract, what is the schedule of their injections?

Answer 27

Less frequent, every 4 weeks

Question 28

How long does it take for severe reactions to manifest after SIT?

Answer 28

Within 20minutes of the injection, and a minimum observation period of 30minutes after injections is widely accepted as appropriate.

Question 29

Can SIT be started during pregnancy?

Answer 29

Current advice is that it should not be started, but maintenance treatment may be continued, provided there is no history of systemic reactions.

Question 30

_____ of patients do not complete their SIT courses.

Answer 30

10-46%

Question 31

What are the standardized extracts available for SLIT?

Answer 31

HDM (Dermatophagoides farinae and pteronyssinus), cat dander, weeds (ragweed, Parietaria, mugwort), grasses, and tree pollens.

Question 32

SLIT doses are _______ times those used in SCIT.

Answer 32

50-110x

Question 33

Are local side effects common in SLIT?

Answer 33

Local effects are common, but systemic effects are rare.

Question 34

How long duration of SLIT is recommended?

Answer 34

3 years or more

Question 35

What is the mechanism of action of SLIT?

Answer 35

The fraction that is retained in the oral mucosa is taken up by the dentritic cells that migrate to regional lymph nodes.

Question 36

How long do allergens persist in the mouth?

Answer 36

up to 20 hours after SLIT

Question 37

What are the immunologic changes associated with successful SLIT?

Answer 37

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.

Question 38

Blocks the Th2 response and decreases the activation of mast cells and eosinophils?

Answer 38

TGF-b1

Question 39

What is a consistent finding in most SLIT studies using large dose of allergen?

Answer 39

Induction of allergen-specific IgG4

Question 40

What are the mechanisms of SLIT? (7)

Answer 40

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.

Question 41

Percentage reduction in symptom score and rescue medication use in patients with seasonal allergic rhinitis after SLIT?

Answer 41

30-40% reduction

Question 42

SLIT appears to reduce asthma symptoms and medication scores after _____ years of treatment.

Answer 42

2 years

Question 43

Rate of serious systemic side effects of SCIT in patients with rhinitis?

Answer 43

1 in 500 injections

Question 44

What are the local side effects of SLIT?

Answer 44

Itching of the mouth and palate

Question 45

What is the overall frequency of systemic adverse reactions to SLIT?

Answer 45

1 in 3000 doses

Question 46

What is another potential mode of administration for SIT?

Answer 46

Intralymphatic route

Question 47

Percentage reduction in symptom score and rescue medication use in patients with seasonal allergic rhinitis after SLIT?

Answer 47

30-40% reduction

Question 48

SLIT appears to reduce asthma symptoms and medication scores after _____ years of treatment.

Answer 48

2 years

Question 49

Rate of serious systemic side effects of SCIT in patients with rhinitis?

Answer 49

1 in 500 injections

Question 50

What are the local side effects of SLIT?

Answer 50

Itching of the mouth and palate

Question 51

What is the overall frequency of systemic adverse reactions to SLIT?

Answer 51

1 in 3000 doses

Question 52

What is another potential mode of administration for SIT?

Answer 52

Intralymphatic route