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Middleton's Allergy Essentials > Chapt. 6: Allergen-specific Immunotherapy > Flashcards

Chapt. 6: Allergen-specific Immunotherapy Flashcards

1
Q

What is the mechanism of action for SIT?

A

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.

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2
Q

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

A

SIT

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3
Q

How long is the build-up phase of SIT?

A

7-12 weeks

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4
Q

How long are the monthly maintenance injections for SIT?

A

3 years

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5
Q

What are the 3 main indications for SIT?

A

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

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6
Q

Risk factor for adverse reaction to SIT?

A

Unstable asthma

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7
Q

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

A

SIT

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8
Q

How to give SIT for patients with seasonal allergic rhinitis?

A

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

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9
Q

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

A

80%. Symptoms are reduced rather than abolished.

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10
Q

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?

A

6 months

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11
Q

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

A

Airborne fungal spores

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12
Q

What are the main effectors of the allergic response?

A

Eosinophils
Basophils
Mast cells

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13
Q

What are reduced by SIT?

A

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

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14
Q

What increases after SIT?

A

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.

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15
Q

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

A

IL-10 and TGF-B

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16
Q

What is suppressed during SIT?

A

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

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17
Q

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

A

IL-10

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18
Q

What is considered a marker of successful SIT?

A

Increased allergen-specific IL-10

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19
Q

TH2 cells preferentially secrete?

A

IL-4

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20
Q

TH4 cells preferentially secrete?

A

IFN-gamma

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21
Q

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

A

Decrease, increase

22
Q

Promotes Th1 lymphocyte proliferation and suppresses Th2 cells.

A

IL-12.

23
Q

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

A

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

24
Q

What is the maintenance dose of allergens for SIT?

A

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

25
Q

What is the SIT schedule?

A

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.

26
Q

What is the interval of the build-up phase?

A

Injections twice-weekly, weekly, or alternate weeks

27
Q

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

A

Less frequent, every 4 weeks

28
Q

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

A

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

29
Q

Can SIT be started during pregnancy?

A

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

30
Q

_____ of patients do not complete their SIT courses.

A

10-46%

31
Q

What are the standardized extracts available for SLIT?

A

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

32
Q

SLIT doses are _______ times those used in SCIT.

A

50-110x

33
Q

Are local side effects common in SLIT?

A

Local effects are common, but systemic effects are rare.

34
Q

How long duration of SLIT is recommended?

A

3 years or more

35
Q

What is the mechanism of action of SLIT?

A

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

36
Q

How long do allergens persist in the mouth?

A

up to 20 hours after SLIT

37
Q

What are the immunologic changes associated with successful SLIT?

A

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.

38
Q

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

A

TGF-b1

39
Q

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

A

Induction of allergen-specific IgG4

40
Q

What are the mechanisms of SLIT? (7)

A

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.

41
Q

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

A

30-40% reduction

42
Q

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

A

2 years

43
Q

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

A

1 in 500 injections

44
Q

What are the local side effects of SLIT?

A

Itching of the mouth and palate

45
Q

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

A

1 in 3000 doses

46
Q

What is another potential mode of administration for SIT?

A

Intralymphatic route

47
Q

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

A

30-40% reduction

48
Q

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

A

2 years

49
Q

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

A

1 in 500 injections

50
Q

What are the local side effects of SLIT?

A

Itching of the mouth and palate

51
Q

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

A

1 in 3000 doses

52
Q

What is another potential mode of administration for SIT?

A

Intralymphatic route

Middleton's Allergy Essentials (6 decks)

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