Type I hypersensitivity and anaphylaxis Flashcards
State the different forms of immunoglobulins and their roles.
IgG:
- blocks pathogen binding
- activates complement
- opsonise antigen for phagocytes
- transported across placenta
IgM:
- blocks pathogen binding
- activates complement
IgA:
- blocks pathogen binding
- present in tears, digestive juices etc
IgE:
- activates mast cells
IgD:
- not secreted
- function unknown
How are mast cells and basophils activated?
- by cross-linking of the surface of IgE by the antigen
- via complement
- via nerves (axon reflex of sensory nerves, substance P)
- direct contact with pathogen
What is type I hypersensitivity?
Allergic reaction provoked by reexposure to a specific antigen/allergen
What antibody is involved in type I hypersensitivity reaction?
IgE
What happens in a type I hypersensitivity reaction?
- IgE antibodies bind to receptors on the surface of tissue mast cells and blood basophils
- Mast cells and basophils coated by IgE antibodies are “sensitized”
- Later exposure to the same allergen cross-links the bound IgE on sensitized cells, resulting in anaphylactic degranulation
- -> the immediate and explosive release of pharmacologically active pre-formed mediators from storage granules and synthesis of inflammatory lipid mediators from arachidonic acid (histamine, leukotriene and prostaglandin:
What are the effects of the following mediators:
- histamine
- leukotriene
- prostaglandin
Histamine:
- vasodilation
- increased permeability of post-capillary venules
- contraction of smooth muscle
- itch
Leukotriene:
- increased permeability of post-capillary venules
- chemostasis
Prostaglandin:
- arteriolar dilatation
- pain
- fever
What is atopy?
inherited predisposition to produce IgE in response to common environmental antigens
What is IL-4 secreted by, and what does IL-4 do?
Secreted by CD4+ TH2 T cells
Involved in:
1. autocrine stimulation of t-lymphocytes
2. paracrine activation of b-lymphocytes (presenting antigen)
3. delivers instructions to class switch to IgE
What are the clinical manifestations of a type 1 hypersensitivity reaction locally and systemically?
Local:
- allergic rhinitis
- asthma
- eczema
- urticaria
- angioedema
Systemic:
ANAPHYLACTIC shock
How does anaphylactic shock present?
- reduced BP as fluid is leaking into interstitial space and there is dilation of great veins
- peripheries often feel warm
- urticaria, raised itchy rash and erythema
- eyes are sore, red and itchy
- sudden onset of nasal soreness, secretion and sneezing
- angioedema in face, lips, hands, feet, pharynx, larynx [= stridor and resp obstruction]
- bronchoconstriction –> wheeze and resp obstruction
- nausea + vomiting, bloating and metallic taste in mouth
- headache, confusion, loss of consciousness, poor perfusion and intracranial angioedema
- impending sense of doom, cardiac arrest and death
How can anaphylactic shock be treated?
- IM adrenaline (500 micrograms in 0.5 mls)
- Self-administered: epipen, 300 micrograms in 0.3 mls
- Give 50 micrograms by slow IV if circulation is impaired
- Give high flow oxygen
- Give antihistamines such as 10 mg of chlorpheniramine (IM/IV)
- Glucocorticosteroids - 200mg of hydrocortisone
What is anaphylactoid shock? How is it different from anaphylaxis?
Pseudo/non-allergic anaphylaxis
Different because there is not involvement of IgE
How should hereditary angioedema by treated? Why is it treated differently from other kinds of angioedema?
C1 esterase inhibitor
treated differently as it does not respond to adrenaline
What can be used to prevent anaphylaxis is status asthmaticus and chronic urticaria?
Omalizumab