Block E Lecture 2: Allergies Flashcards

1
Q

What is an allergy defined as?

A

Disease following a response by the immune system to an otherwise harmless antigen
(Slide 3)

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2
Q

What percentage of children and adults suffer from allergies?

A

40% of children and 30% of adults
(Slide 3)

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3
Q

What is the most common type of allergen?

A

Proteases
(Slide 5)

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4
Q

Are allergens soluble?

A

Yes, highly
(Slide 5)

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5
Q

Do allergens have intrinsic enzyme activity?

A

Yes - protease activity
(Slide 5)

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6
Q

What 2 things do allergens cleave and activate?

A

Complement components and an inactive form of IL-33 produced by epithelial cells
(Slide 5)

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7
Q

What do protease allergens disrupt?

A

The integrity of the endothelial barrier
(Slide 5)

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8
Q

What do protease allergens stimulate?

A

Protease receptors on immune cells
(Slide 5)

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9
Q

Do allergens contain PAMPS?

A

They can but don’t always
(Slide 5)

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10
Q

Are most airborne antigens big or small?

A

Small
(Slide 6)

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11
Q

What are most airborne allergens carried on?

A

Dry particles
(Slide 6)

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12
Q

What is an allergens first contact called?

A

Sensitisation
(Slide 7)

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13
Q

How does der p 1 enzyme cause allergy?

A

It cleaves occludin in tight junctions and enters mucosa, where it is taken up by dendritic cells for Th2 activation. The Th2 cell then induces B-cell antibody switch to IgE. Der p 1- specific IgE then binds to the FcεRI receptor on mast cell and then upon subsequent exposure to the same allergen (in this case Derp p 1) it binds to IgE already on the surface of immune cells, triggering mast-cell degranulation, causing allergic symptoms
(Slide 7)

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14
Q

What immune cells express the FcεRI receptor?

A

Mast cells, basophils and eosinophils (to a lesser extent)
(Slide 9)

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15
Q

When does cross linking occur?

A

Cross-linking occurs when the allergen binds simultaneously to the Fab (antigen-binding) regions of two or more IgE antibodies bound to adjacent FcεRI receptors
(Slide 9)

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16
Q

What 2 things happen when IgE is cross-linked to an antigen?

A

Expression of CD40L and release of IL-4
(Slide 9)

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17
Q

What do CD40L and IL-4 produced by IgE cross-linking signal?

A

For the B cells to produce more IgE
(Slide 9)

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18
Q

What are 2 things which normal degranulation cause and how do these help clear parasites?

A

Causes vasodilation
Increased vascular permeability

These result in an influx of immune and plasma mediators to the site of infection to attack the pathogen
(Slide 10)

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19
Q

How does degranulation harm the body in an allergic response?

A

Unnecessary increases in vascular permeability and inflammation leading to tissue damage with no benefit
(Slide 10)

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20
Q

What percent of mast cell granules does histamine account for?

A

10%
(Slide 11)

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21
Q

How long does histamine take to take effect?

A

Minutes
(Slide 11)

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22
Q

What receptor does histamine bind?

A

Histamine receptors (H1-4)
(Slide 11)

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23
Q

What are 4 examples of the effects of histamine?

A

Contraction of intestinal and bronchial smooth muscle
Increased permeability of veins
Increased mucus secretion
Increased stomach acid
(Slide 11)

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24
Q

How are leukotrienes and prostaglandins formed?

A

By the break-down of phospholipids in the cell membrane
(Slide 12)

25
Q

What do leukotrienes and prostaglandins cause?

A

Further smooth muscle concentration (in the bronchia and trachea) with leukotrienes also causing vascular permeability and mucus secretion
(Slide 12)

26
Q

What do leukotrienes and prostaglandins play a significant role in?

A

Asthma
(Slide 12)

27
Q

What 2 things does degranulation cause in the gastrointestinal tract (GI tract) and what does this lead to?

A

Increased fluid secretion and peristalsis - leading to diarrhea and vomiting
(Slide 13)

28
Q

What 2 things does degranulation cause in the eyes, nasal pathways and airways and what does this lead to?

A

Decreased airway diameter and increased mucus secretion leading to congestion, blocking of airways, swelling and mucous secretion in nasal passages
(Slide 13)

29
Q

What are IL-4 and IL-13 important in directing and what does this lead to?

A

Th2 response - leading to more IgE production by B-cells
(Slide 14)

30
Q

What do IL-3 and IL-5 do?

A

Promote eosinophil production and activation
(Slide 15)

31
Q

What 3 things are release in the early (within 30 mins) response of IgE mediated allergic reactions (Type 1 hypersensitivity)?

A

Histamine, prostaglandins and leukotrienes
(Slide 16)

32
Q

What happens in the late (between 6-12 hours) response of IgE mediated allergic reactions (Type 1 hypersensitivity)?

A

Cytokines increase chemokine expression and cell adhesion molecules, helping influx of neutrophils, eosinophils and Th2 cells, cytokines also induce growth and differentiation of eosinophils which are then triggered to degranulate by binding antibody-allergen complexes
(Slide 16)

33
Q

What 2 categories of reactions can type 1 hypersensitivity by divided into?

A

Localised
Systematic
(Slide 19)

34
Q

What are 2 examples of localised type 1 hypersensitivity reactions?

A

Hay-fever and atopic dermatitis
(Slide 19)

35
Q

What are 2 examples of systematic type 1 hypersensitivity reactions?

A

Anaphylaxis and severe asthma
(Slide 19)

36
Q

What 3 things decide the category of type 1 hypersensitivity that occurs?

A

The route of administration
Concentration
Prior exposure to the allergen
(Slide 19)

37
Q

What is systemic anaphylaxis?

A

A severe systemic and often fatal event
(Slide 20)

38
Q

How long does it take after allergen exposure for systemic anaphylaxis to occur?

A

Minutes
(Slide 20)

39
Q

What are 3 symptoms of systemic anaphylaxis?

A

Dangerous drop in blood pressure - anaphylactic shock
Concentration of smooth muscle
Laboured respiration - asphyxiation
(Slide 20)

40
Q

How does anaphylaxis kill in 2-4 mins?

A

Through asphyxiation
(Slide 20)

41
Q

What is the cause of systemic anaphylaxis?

A

Rapid and widespread IgE-mediated degranulation of mast cells and basophils
(Slide 20)

42
Q

Where does hay fever occur?

A

At the epithelial surfaces first exposed to the allergen
(Slide 21)

43
Q

What causes hay fever?

A

Inhalation of airborne allergens causing sensitised mast cells resident in nasal mucosa to degranulate
(Slide 21)

44
Q

What are 3 symptoms of hay fever?

A

Tearing, running nose and coughing
(Slide 21)

45
Q

What does the term asthma describe?

A

Attacks of breathlessness and wheezing
(Slide 22)

46
Q

Where does asthma occur?

A

In the lower respiratory tract
(Slide 22)

47
Q

How does asthma occur?

A

Similarly to hay fever - sensitised mast cells degranulate on exposure to the antigen
(Slide 22)

48
Q

What 3 things does asthma trigger?

A

Bronchial constriction and airway obstruction
(Slide 23)

49
Q

Is the incident rate of food allergies increasing or decreasing?

A

Increasing
(Slide 24)

50
Q

What population are food allergies common in?

A

Infants
(Slide 24)

51
Q

What are 3 symptoms of food allergies?

A

Nausea
Abdominal pain
Vomiting / diarrhoea
(Slide 24)

52
Q

How long does it take food allergies to occur?

A

Minutes - hours
(Slides 24)

53
Q

How are cells in food allergies sensitised to the allergen?

A

Through the skin (or intestine) via disruption of the epithelial layer with epithelial cells responding to the stimuli
(Slide 25)

54
Q

What does atopic mean?

A

Sensitivity to allergens
(Slide 27)

55
Q

What is the hygiene hypothesis in the context of allergies?

A

Exposure to infections and common environmental organisms at an early age = non-atopy (no suspectable to allergies)
(Slide 27)

56
Q

What are 4 ways to treat allergies?

A

Drugs
Medications
Adrenaline (Epinephrine) administered through an epi-pen
Immunotherapies (anti-IgE antibodies) to desensitise the body
(Slide 29)

57
Q

How are medications used to treat anaphylaxis?

A

To help prevent degranulation of mast cells by enhancing cAMP production
(Slide 29)

58
Q

What does treating allergies by desensitisation involve?

A

Injecting or ingesting low or increasing doses of allergen to induce immune tolerance
(Slide 30)