Hypersensitivity & Anaphylaxis Flashcards
Define hypersensitivity.
An inappropriate + excessive immunological reaction to an external antigen due to dysfunctional control of the immune system
What is the difference between allergy and anaphylaxis?
Allergy = local reaction e.g. mucous membranes, skin + lungs
Anaphylaxis = systemic reaction including shock + death
Define allergen.
Antigen that induces a hypersensitivity reaction
Define autoimmunity.
An inappropriate + excessive immunological reaction to a self-antigen/auto-antigen due to dysfunctional control of the immune system (including a loss of tolerance)
What are the 4 types of hypersensitivity reactions?
I: immediate/IgE-mediated
II: Ab-dependent
III: Immune complex
IV: Delayed/cell-mediated
What is atopy?
Predisposition to allergies in general (e.g. eczema, asthma, hayfever) so often familial/genetic
What are the mediators of type II hypersensitivity reactions?
IgM/IgG
What are some examples of type II hypersensitivity reactions?
Autoimmune haemolytic anaemia
Goodpasture’s syndrome
Mysasthenia gravis
Graves’ disease
What are the mediators of type III hypersensitivity reactions?
Immune complex i.e. Ag-Ab complex
What are some examples of type III hypersensitivity reactions?
Serum sickness
Extrinsic allergic alveolitis (EAA)
Rheumatoid arthritis (RA)
Systemic lupus erythematosus (SLE)
What are the mediators of type I hypersensitivity reactions?
IgE+ mast cells
What are the mediators of type IV hypersensitivity reactions?
T lymphocytes (usually cytotoxic T cell response)
What are some examples of type I hypersensitivity reactions?
Allergies (most)
Anaphylaxis
Asthma
Atopy
What are some examples of type IV hypersensitivity reactions?
Allergic contact dermatitis
Chronic transplant rejection
Multiple sclerosis (MS)
Tuberculin skin test (TST)
Where are type I hypersensitivity reactions most common?
Developed countries
What allergens can cause the various diseases in type I hypersensitivity?
Pollen, house dust mites + animal dander -> hayfever + allergic rhinitis
Insect venom, food + drugs -> anaphylaxis usually
Often idiopathic -> asthma + atopic eczema
What is the pathology of type I hypersensitivity reactions?
- First exposure to allergen where crosslinking occurs with B cells
- Activation of Th2 cells
- Stimulation of IgE class switching of B cells
- Production of IgE
- Crosslinking of IgE to FceRI on mast cells
- Second exposure to allergen will stimulate mast cell degranulation + mediator release (symptoms appear)
What mediators are involved in type I hypersensitivity reactions and what types of reactions can these cause?
Immediate (mins after 2nd exposure to allergen): vasoactive amines + lipid mediators
Late phase (6-24hrs after 2nd exposure to allergen): cytokines
What symptoms does granule exocytosis of mast cells cause in type I hypersensitivity reactions?
Vasoactive amines -> vascular dilation + SM contraction
Proteases -> tissue damage
What are the symptoms of type I hypersensitivity?
Pruritis Sneezing Rhinorrhoea Lacrimation Urticaria Angioedema
What are the symptoms of type I hypersensitivity if the allergen was exposed to the patient systemically?
Local swelling Flushing Fainting Dyspnoea Peri-oral paraesthesia Throat/chest tightness Wheeze Pale Sweaty Hypotensive collapse Unconscious Death
What is the main difference between type I and type IV hypersensitivity reactions?
Type IV are slower + more specific than type I
What allergens can cause the various diseases in type IV hypersensitivity?
Nickel, metals, formalin + latex -> ACD
What are some anomaly examples of type IV hypersensitivity?
Chronic organ rejection
Autoimmune e.g. MS
Diagnostic e.g. TST
-> not truly excessive or inappropriate
How do you investigate hypersensitivity reactions?
- Measure blood markers e.g. tryptase, IgE + eosinophil
2. Skin prick testing to identify exact allergen
How do you carry out a skin prick test?
- Apply solution of appropriate test allergens plus -ve & +ve controls (saline + histamine respectively) to skin
- Prick through solution into skin + read results after 15 mins
- +ve result = lesion > 3mm larger than -ve control
What is the difference between a skin prick and skin patch test?
More allergens are tested than in the skin prick test + the patient goes away for a week so there is longer contact times
What is the main treatment for hypersensitivity reactions?
Avoid the allergen
What drugs can be used to treat hypersensitivity reactions? How do they work?
- Mast cell stabilisers (usually topical) -> prevent mast cell degranulation
- Anti-histamines (topical/systemic) -> block histamine receptor + effects
- Steroids (topical/systemic) -> wide ranging anti-inflammatory effects
- LT receptor antagonists (systemic) -> block LT effects
What is de-sensitisation treatment?
Relies on creating tolerance to allergens by gradual exposure increasing doses delivered sublingually or subcutaneously (also called allergen immunotherapy)
Requires weekly/monthly treatment for 3 years
What is a potential risk of de-sensitisation treatment?
Anaphylaxis
What treatment do you give for anaphylaxis?
- Lie patient down
- High flow O2
- IV fluids
- IM adrenaline (EpiPen)
- IV chlorphenamine (anti-histamine), IV hydrocortisone (steroid) or nebulised salbutamol (bronchodilator)
- Repeat EpiPen if no improvement after 5 mins
What is the pneumonic used to remember anaphylaxis treatment?
A - airway
B - breathing
C - circulation
How should you administer an EpiPen?
- Form fist around it + pull off grey safety cap
- Place back end against out mid-thigh (with/without clothing)
- Push down hard until a click is heard/felt + hold in place for 10 seconds
- Remove EpiPen + do not touch needle
- Massage injection site for 10 seconds
What symptoms does enzymatic modification of arachidonic acid in mast cells cause in type I hypersensitivity reactions?
Lipid mediators produced:
- PGs -> vascular dilation
- LTs -> SM contraction
What symptoms does transcriptional activation of cytokine genes in mast cells cause in type I hypersensitivity reactions?
Secretion of cytokines e.g. TNF -> inflammation + leukocyte recruitment
What are the 3 pathways that get triggered when the allergen binds the mast cell in type I hypersensitivity reactions?
- Granule with preformed mediator exocytosis
- Enzymatic modification of arachidonic acid
- Transcriptional activation of cytokine genes