Type 1 Hypersensitivty = Allergy

Question 1

What can immediate allergic reactions be divided into?

Answer 1

<30mins

Local reaction - ingested or inhaled allergen
Systemic reaction - insect sting or IV administration (reaches circulation)

Question 2

Type 1 hypersensitivity exposures

Answer 2

Seasonal exposures - tree/ grass pollens

Perennial exposure (all year round) - house dust mites/ animal dander/ fungal spores

Accidental exposure - insect venom/ medicines/ chemicals e.g. latex/ foods

Question 3

Mechanism of type 1 hypersensitivity

Answer 3

Abnormal adaptive immune response against the allergens:
- T helper 2 response (IL-4, IL-5, IL-13)
- IgE production
(Normal is TH1-> IgG)
Allergen 1st exposure - TH2 response, 2nd exposure IgE cross- linking (antigen specific) -> direct activation of mast cells -> mast cell degranulation

Mast cell activation (sensitised individuals, depends on mast cell location) - triggering remakes of granule contents e.g. histamines/ chemokines + synthesis of new mediators e.g. leukotrienes/ prostaglandins -> increased vascular permeability/ vasodilation/ bronchial constriction

Question 4

Why do ppl have allergies?

Answer 4

Hygiene hypothesis - less infectious burden when young -> more likely to be hypersensitive, more likely in developed countries

Prevention factors: large family, intestinal micro flora- variable, low antibiotic use, high helminth burden

+ genes

Question 5

What’s the old friends or biodiversity hypothesis?

Answer 5

Western lifestyle
(e.g. antibiotic use, C-sections, junk food)
induces alteration of symbiotic relationships with parasites & bacteria -> dysbiosis* of the microbiota at mucosal surfaces e.g. gut

*compositional and functional alterations of microbiome

Question 6

Impact of dysbiosis on human diseases

Answer 6

Increased risk allergies
Colorectal cancer 
Autism 
Metabolic diseases (obesity, DM2)
Immune diseases (crohn’s, ulcerative colitis, DM1, celiac disease, multiple sclerosis)

Question 7

How are mast cells strategically localised? How does the IgE- dependent mechanism of activation change mast cells?

Answer 7

Most mucosal and epithelial tissues = GI tract, skin, resp epithelium , in CT surrounding blood cells

Activated mast cells are de-granulated to release their mediators

Question 8

Mast cell mediators examples and biological effects

Answer 8

Typtase/ Chumash - remodels CT matrix

Histamine/ heparin - toxic time parasites, increase vascular permeability, Sm contraction

IL-4/13 - stimulate and amplify TH2 cell response
IL-3/5 - promote eosinophilic production & activation
TNF- alpha - promotes inflammation, stimulates cytokines production

Leucotrienes- SM contraction, increase vascular permeability, stimulates mucus secretions
Platelet- activating factor - attracts leukocytes, activates neutrophils/ eosinophils/ platelets

Question 9

What can be measured in blood as a marker for anaphylaxis?

Answer 9

Tryptase

Question 10

Skin manifestations of allergic reactions, cause

Answer 10

Urticaria - aka hives, raised/ itchy areas of skin
(Wheals flat patches between)

Caused by mass cell activation within epidermis (vasodilation)

Mediators - histamine, leuktrienes, cytokines

If prolonged and chronic exposure -> atopic dermatitis & eczema

Question 11

Face manifestations of allergic reactions and cause

Answer 11

Angioedema - acute or chronic disorder that affects mucous membranes & deepest layers of skin along with underlying tissues, non itchy swelling e.g. lips, eyes, tongue, upper respiratory airways

Mast cell activation in deep dermis

Mediators - histamine and bradykinin

Can cause life threatening airway obstruction

Question 12

Systemic manifestations of allergic reactions

Answer 12

Anaphylaxis

Systemic activation of mast cells

• hypotension (CVS collapse, lose 30% blood volume in 10mins)
• generalised urticaria
• angioedema
• breathing problems (wheezing, stridor)
• confusion/ loss consciousness
• anxiety
• cramps abdo pain
• diarrhoea
• vomiting
• Loss bladder control
• hives
• swelling conjunctiva

Acute, rapidly progressing, involving skin +1 other organ system or no skin involvement, bronchoconstriction/ hypotension/ GI problems

Question 13

Treatment of anaphylactic shock

Answer 13

Epinephrine (adrenaline) IM

Reverses peripheral vasodilation and reduces oedema and alleviate hypotension, reverses airways obstruction/ bronchospasm, increases force of myocardial contraction, inhibits mast cell activation

Monitor pulse, BP, ECG, oximetry

30% biphasic (need 2nd dose)

Question 14

Type 1 hypersensitivity therapy

Answer 14

Abnormal adaptive immune response against the allergens: give oral immunotherapy -> allergen desensitisation, prevents TH2 response - increasing doses of allergen extracts years injection/ drops/ tablets/ sublingual (90% effective bee/ wasp venom)
Or anti-IgE monoclonal antibody to stop IgE

Mast cell activation: (inhibit mediators) anti-histamine, leukotriene receptor antagonists, corticosteroids

Question 15

What are potential mechanisms for why immunotherapy/ allergen desensitisation works?

Answer 15

Involves administration of increasing doses of allergen extracts over years, injection/ drops/ tablets/ sublingual

Potential mechanisms: CD4+CD25 regulatory T cells, shift from TH2 to TH1, inhibitory anti-inflammatory cytokines, allergen specific blocking IgG

90% effective bee/ wasp stings
62% effective peanuts