2. Type 1 Hypersensitivity Reactions Flashcards
What is the onset of type 1 reactions?
Immediate reaction (<30min)
What typically causes local type 1 reactions?
Ingested or inhaled allergens
WHat typically causes systemic type 1 reactions?
Insect sting or IV administration
what determines which organs are effected?
depend on where the mast cells and IgE are activated
which type of reaction is anaphylaxis?
systemic reaction - massive mast cell activation and degranulation
what are the antigens for type I hypersensitivity?
allergen - usually harmless
o Environmental, non-infectious antigens (proteins)
Give examples of seasonal allergens
Tree and grass pollens
Give examples of perennial allergens.
- House dust mite
- Animal dander = cats and dogs
- Fungal spores
Give examples of accidental exposure to allergens.
- Insect venom (wasp and bee stings)
- Medicines - for example, the antibiotic penicillin
- Chemicals such as latex
- Foods: milk, peanuts, nuts, etc…
What is involved in type 1 reactions?
• 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
what does the Different clinical allergic disorders depend on?
mast cell location
describe what happens during type 1 reaction
- 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
what are some action of heparin?
smooth muscle contraction of bronchi - difficulty breathing
vasodilation and increased vascular permeability - oedema and urticaria
What is the hygiene hypothesis?
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
What is the biodiversity hypothesis?
Western lifestyle induces alteration of the symbiotic relationships with parasites and bacteria leading to “dysbiosis” of the microbiome at mucosal surfaces (gut)
Define dysbiosis.
compositional and functional alterations of microbiome
What are some causes of dysbiosis in western countries?
Lifestyle, eating behaviours, disruption of biological clock and antibiotic consumption
Where are mast cells found?
- Most mucosal and epithelial tissues = gastrointestinal tract, skin, respiratory epithelium
- In connective tissue surrounding blood cells
what’s the significance of mast cells being found in mucosal tissues?
can counter any parasites
WHat are some mast cell mediators and their actions?
- 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)
Describe the mechanism of type 1 reactions?
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
What receptor do IgE bind to on mast cells?
Fc portion of IgE bind to FcεR1, or Fc epsilon R1
What is a skin manifestation of an allergic reaction?
Urticaria
What causes urticaria, what mediators are involved?
- Caused by mast cell activation within the EPIDERMIS
- Mediators = Histamine and leukotrienes/cytokines
What does prolonged activation of mast cells within the epidermis lead to
atopic dermatitis and eczema
what are the hives/urticaria due to?
fluid accumulation under skin due to vasodilation
What is a face manifestation of an allergic reaction?
Angioedema
- non itchy swelling
What causes angioedema, what mediators are involved?
- Caused by mast cell activation in the DEEP DERMIS.
- Mediators = Histamine and bradykinin
which part of the body are affected bu angioedema?
lip
eyes
airway obstruction emergency:
tongue
upper respiratory airways
What are the effects of systemic activation of mast cells?
Anaphylaxis:
increased vascular permeability:
- Hypotension
- Cardiovascular collapse
- Generalized urticaria
vasodilation:
- Angioedema
bronchoconstriction:
- Breathing problems
what causes systemic activation of mast cells?
systemic absorption of allergen
Define anaphylaxis
Acute onset hypersensitivity reaction, rapidly progressing, involving the skin and 1 other system (CV, Resp, GI)
What is the treatment for anaphylaxis?
Epinephrine(adrenaline)
How does adrenaline help in anaphylaxis?
- Reverses peripheral vasodilation and reduces oedema and alleviates hypotension
- Reverses airway obstruction / bronchospasm
- Increases the force of myocardial contraction
- Inhibits mast cell activation
What should be monitored in treatment of anaphylaxis?
Monitor pulse, blood pressure, ECG, oximetry
What can be used to treat type 1 hypersensitivity reactions targeting the abnormal adaptive immune response?
o TH2 response = Allergen desensitization (oral immunotherapy)
o Omalizumab = Anti-IgE monoclonal antibody o Mepolizumab – Anti-IL5 monoclonal antibody
What can be used to treat type 1 hypersensitivity reactions targeting mast cell activation?
o Anti-histamine - reduced vascular permeability and bronchoconstriction
o Leukotriene receptor antagonists
o Corticosteroids - reduced inflammatory response
what is Allergen desensitization or immunotherapy?
“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)”
what are the possible mechanisms for Allergen desensitization ?
- CD4+CD25 Regulatory T cells
- Shift from TH2 to TH1
- Inhibitory anti-inflammatory cytokines
- Allergen specific blocking IgG
what are 2 important factors for the development of allergic diseases?
A reduced infectious burden coupled to changes in the microbiome
how is epinephrine administered?
intramuscular injection
