Week 5- Anaphylaxis Flashcards
Give two examples of a hyperactive immune system
Hypersensitivity and Autoimmunity
Define hypersensitivity Contrast to definition of autoimmunity
Hypersensitivity= an inappropriate and excessive immune response to an external allergen due to dysfunctional control of the immune system. Autoimmunity= an inappropriate and excessive immunological reaction to a sekf/auto antigen due to dysfunctional control of the immune system.
Define allergy
Local reaction to an external antigen/allergen to which the immune system has become hypersensitive (Mucous membranes/ skin/ lungs).
Define anaphylaxis
A life threatening systemic allergic reaction which can result in shock and death.
Define allergen
an external antigen which results in hypersensitivity reaction
What types of hypersensitivity reactions are there?
What is each mediated by?
Give examples of each type of hypersensitivity reaction
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Type 1: Immediate or IgE mediated:
- Cell mediator = mast cell
- examples of type 1 reactions include: Allergies/ Asthma/Atopy/ Anaphylaxis
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Type 2: Antibody dependent (IgG/ IgM):
- Mediated by IgM/IgG
- Examples include: Myasthenia gravis, Graves disease, autoimmune haemolytic anaemia
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Type 3: Immune complex mediated:
- Mediated by antigen-antibody complex
- Examples include: rheumatoid arthritis, systemic erythematous lupus, serum sickness
-
Type 4: Delayed/ Cell mediated:
- Mediated by T lymphocytes
- Less aggressive and not as life threatening as type 1 reactions
- examples include: allergic contact dermatitis, chronic transplant rejection, Tuberculin skin test
Give examples of allergens and what reactions they tend to induce
- House dust/ pollen/ mites/ animal dander:
- hayfever/ atopy/ allergic rhinitis
- Venom/ food/ drugs:
- anaphylaxis more likely
- Idiopathic tends to be asthma and atopic eczema
Describe the pathology of Type 1 hypersensitivity reactions:
How does the first phase of the reaction occur?
Sensitisation phase: First exposure to allergen:
- Exposure to the allergen
- Activation of IgE secreting B cell by binding of allergen to correct receptor on B cell which becomes activated to secrete IgE specific to that allergen with aid of Th2 cells.
- IgE production, and binding to receptors on mast cells
- Next exposure to allergen will cross link the mast cell receptors leading to mast cell activation and degranulation.
Describe the pathology of Type 1 hypersensitivity reactions:
How does the second phase of these reactions occur?
Second phase: rexposure to allergen and Mast cell degranulation
- Re exposure to allergen cross links the IgE expressed on surface of mast cell bound to cell surface receptors
- Leads to intracellular signalling pathways that induce:
- 1) transcription of cytokine genes, production and release
- 2) release of pre formed cytoplasmic granules with proteases and vasoactive amines
- 3) Production of lipid signalling mediators ( Leukotriene and Prostaglandins from AA).
- Release of pre formed granule with proteases and vasoactive amine leads to tissue damage, vasodilation and smooth muscle contraction- immediate phase of allergic reaction
- Lipid signalling mediators also lead to vasodilation and SMC contraction
- Release of cytokines sets up delayed phase which attracts more immune cells to area- inflammation.
What is pruritus?
What is urticaria?
What is angioedema?
Pruritis- severe itching of skin/ body region
Urticaria = hives, oedematous itchy lesions within the skin
Angioedema= swelling of skin underneath skin or mucous membrane
What are the clinical features of Type 1 hypersensitivity reactions?
- Airways and eye mucous membranes:
- Pruritis, sneezing, rhinorrhea, lacrimation
- Skin:
- pruritus , urticaria
- Mouth and intestinal mucous membranes:
- Pruritus and angiooedema
- Anaphylaxis:
- Pale/ Flushed/ Sweaty
- Dyspnoea/ Wheezing/ Chest tightness
- Perioral parasthesia (odd sensation/ tingling/ numbness lips)
- Hypotension, dizziness/ fainting
- Unconciousness
- death
What are the clinical features of Type 4 hypersensitivity reactions?
Give an example of a common condition that is a type 4 hypersensitivity reaction
Give an example of a clinical test that involves inducing a type 4 reaction
- Delayed/ Cell mediated= Type 4 hypersensitivity reaction
- Requires T cytotoxic lymphocytes to sensitise to allergen
- Slowly developing/ Chronic
- Highly specific and therefore localised immune reaction
- Common allergens: Metals e.g. nickel and latex
- Common condition : Allergic contact dermatitis:
- Chronic, pruritus and oedematous lesion developing in localised region on skin after contact with allergen
- Clinical test: Tuberculin skin test- prick skin with TB antigens, if preexposed will develop type 4 reaction within week.
What investigations could be done to determine whether there is a Type 1 reaction present?
What tests could be done to determine the allergen?
- Type 1 reaction- take blood sample and look for: tryptase, raised levels of IgE antibodies and eosionphils
- To determine allergen use either:
- skin prick test- different allergens injected under the skin with positive and negative controls (saline and histamine), if allergic will develop lesion 3mm larger than negative control after 15 mins).
- Patch testing- larger version of skin prick test with commerical pads with allergen pressed onto skin and left. Response checked after a week.
What treatments are there for hypersensitivity?
A M A S L (A MASt ceLl)
A- Avoidance of allergen
M- mast cell stabilisers, usually topical (eye drops/ nasal spray)
A- antihistamine - block histamine receptors- can be topical (drops/spray) or systemic (tablets)
S- steroids- wide ranging antiinflammatory effects, topical w spray or systemic w tablets
L- Leukotriene Receptor antagonists - block leukotriene receptors
What is the treatment for anaphylaxis?
- Airway Breathing Circulation:
- Lie patient flat (circulation)
- High flow oxygen
- IV fluids
- Intramuscular injection Adrenaline (500 mcg) (if given via IV can produce cardiac arrhythmias)
- IV antihistamine - Chlorphenamine
- IV steroid - hydrocortisone
- Bronchodilator- nebulised salbutamol
- If no response to Adrenaline after 5 mins repeat IM injection