2. Type 1 Hypersensitivity Reactions

Question 1

What is the onset of type 1 reactions?

Answer 1

Immediate reaction (<30min)

Question 2

What typically causes local type 1 reactions?

Answer 2

Ingested or inhaled allergens

Question 3

WHat typically causes systemic type 1 reactions?

Answer 3

Insect sting or IV administration

Question 4

what determines which organs are effected?

Answer 4

depend on where the mast cells and IgE are activated

Question 5

which type of reaction is anaphylaxis?

Answer 5

systemic reaction - massive mast cell activation and degranulation

Question 6

what are the antigens for type I hypersensitivity?

Answer 6

allergen - usually harmless

o Environmental, non-infectious antigens (proteins)

Question 7

Give examples of seasonal allergens

Answer 7

Tree and grass pollens

Question 8

Give examples of perennial allergens.

Answer 8

• House dust mite
• Animal dander = cats and dogs
• Fungal spores

Question 9

Give examples of accidental exposure to allergens.

Answer 9

• Insect venom (wasp and bee stings)
• Medicines - for example, the antibiotic penicillin
• Chemicals such as latex
• Foods: milk, peanuts, nuts, etc…

Question 10

What is involved in type 1 reactions?

Answer 10

• Abnormal adaptive immune response against the allergens
o T helper 2 (TH2) response (IL-4, IL-5, IL-13) which leads to
o IgE production

• Mast cell activation - by binding of allergen specific IgE
o Sensitized individuals

Question 11

what does the Different clinical allergic disorders depend on?

Answer 11

mast cell location

Question 12

describe what happens during type 1 reaction

Answer 12

• antigen presenting cells pick up the antigen and present it to naive T helper cells in lymph nodes.
• naive t helper cells once bound to antigen, differentiate into TH2 cells which release interleukins that cause B cells to switch from making IgG antibodies to IgE.
• interleukin 5 also stimulates production and activation of eosinophils.
• Fc portion of IgG antibodies bind to Fc receptors on mast cells. mast cells are sensitised.
• if same exposed to same allergen, IgE antibodies on mast cells bind to allergen.
• antigen bind to 2 or more IgE antibodies to crosslink and cause mast cells to degranulate and release proinflammatory mediators like histamine, leukotriene, prostaglandin, heparin

Question 13

what are some action of heparin?

Answer 13

smooth muscle contraction of bronchi - difficulty breathing

vasodilation and increased vascular permeability - oedema and urticaria

Question 14

What is the hygiene hypothesis?

Answer 14

Children exposed to animals, pets and microbes in the early postnatal period appear to be protected against certain allergic diseases - favours TH1 response so IgG produced and less IgE

Question 15

What is the biodiversity hypothesis?

Answer 15

Western lifestyle induces alteration of the symbiotic relationships with parasites and bacteria leading to “dysbiosis” of the microbiome at mucosal surfaces (gut)

Question 16

Define dysbiosis.

Answer 16

compositional and functional alterations of microbiome

Question 17

What are some causes of dysbiosis in western countries?

Answer 17

Lifestyle, eating behaviours, disruption of biological clock and antibiotic consumption

Question 18

Where are mast cells found?

Answer 18

• Most mucosal and epithelial tissues = gastrointestinal tract, skin, respiratory epithelium
• In connective tissue surrounding blood cells

Question 19

what’s the significance of mast cells being found in mucosal tissues?

Answer 19

can counter any parasites

Question 20

WHat are some mast cell mediators and their actions?

Answer 20

• tryptase (remodel connective tissue matrix)
• histamine (vasodilation, vascular permeability, contraction of non vascular smooth muscle)
• leukotrienes C4, D4 and E4 (vasodilation, vascular permeability, stimulate mucus secretion, contraction of non vascular smooth muscle)
• IL-4, IL-13 (stimulate and amplify TH2 response)
• IL-5 (promote eosinophil production and activation)

Question 21

Describe the mechanism of type 1 reactions?

Answer 21

Sensitisation:

• exposure to allergen
• Th2 response
• plasma cell production of IgE
• IgE bind to mast cells

Effector:

• Re-exposure to allergen
• allergen binds to 2 IgE molecules on mast cells surface
• mast cells activation and degranulation
• increased vascular permeability, vasodilation, bronchial constriction

Question 22

What receptor do IgE bind to on mast cells?

Answer 22

Fc portion of IgE bind to FcεR1, or Fc epsilon R1

Question 23

What is a skin manifestation of an allergic reaction?

Answer 23

Urticaria

Question 24

What causes urticaria, what mediators are involved?

Answer 24

• Caused by mast cell activation within the EPIDERMIS

- Mediators = Histamine and leukotrienes/cytokines

Question 25

What does prolonged activation of mast cells within the epidermis lead to

Answer 25

atopic dermatitis and eczema

Question 26

what are the hives/urticaria due to?

Answer 26

fluid accumulation under skin due to vasodilation

Question 27

What is a face manifestation of an allergic reaction?

Answer 27

Angioedema

- non itchy swelling

Question 28

What causes angioedema, what mediators are involved?

Answer 28

• Caused by mast cell activation in the DEEP DERMIS.

- Mediators = Histamine and bradykinin

Question 29

which part of the body are affected bu angioedema?

Answer 29

lip
eyes

airway obstruction emergency:

tongue
upper respiratory airways

Question 30

What are the effects of systemic activation of mast cells?

Answer 30

Anaphylaxis:

increased vascular permeability:

• Hypotension
• Cardiovascular collapse
• Generalized urticaria

vasodilation:
- Angioedema

bronchoconstriction:
- Breathing problems

Question 31

what causes systemic activation of mast cells?

Answer 31

systemic absorption of allergen

Question 32

Define anaphylaxis

Answer 32

Acute onset hypersensitivity reaction, rapidly progressing, involving the skin and 1 other system (CV, Resp, GI)

Question 33

What is the treatment for anaphylaxis?

Answer 33

Epinephrine(adrenaline)

Question 34

How does adrenaline help in anaphylaxis?

Answer 34

• Reverses peripheral vasodilation and reduces oedema and alleviates hypotension
• Reverses airway obstruction / bronchospasm
• Increases the force of myocardial contraction
• Inhibits mast cell activation

Question 35

What should be monitored in treatment of anaphylaxis?

Answer 35

Monitor pulse, blood pressure, ECG, oximetry

Question 36

What can be used to treat type 1 hypersensitivity reactions targeting the abnormal adaptive immune response?

Answer 36

o TH2 response = Allergen desensitization (oral immunotherapy)
o Omalizumab = Anti-IgE monoclonal antibody o Mepolizumab – Anti-IL5 monoclonal antibody

Question 37

What can be used to treat type 1 hypersensitivity reactions targeting mast cell activation?

Answer 37

o Anti-histamine - reduced vascular permeability and bronchoconstriction
o Leukotriene receptor antagonists
o Corticosteroids - reduced inflammatory response

Question 38

what is Allergen desensitization or immunotherapy?

Answer 38

“It involves the administration of increasing doses of allergen extracts over a period of years, given to patients by injection or drops/tablets under the tongue (sublingual)”

Question 39

what are the possible mechanisms for Allergen desensitization ?

Answer 39

• CD4+CD25 Regulatory T cells
• Shift from TH2 to TH1
• Inhibitory anti-inflammatory cytokines
• Allergen specific blocking IgG

Question 40

what are 2 important factors for the development of allergic diseases?

Answer 40

A reduced infectious burden coupled to changes in the microbiome

Question 41

how is epinephrine administered?

Answer 41

intramuscular injection