Hypersensitivity & Anaphylaxis Flashcards

1
Q

Define hypersensitivity.

A

An inappropriate + excessive immunological reaction to an external antigen due to dysfunctional control of the immune system

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2
Q

What is the difference between allergy and anaphylaxis?

A

Allergy = local reaction e.g. mucous membranes, skin + lungs

Anaphylaxis = systemic reaction including shock + death

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3
Q

Define allergen.

A

Antigen that induces a hypersensitivity reaction

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4
Q

Define autoimmunity.

A

An inappropriate + excessive immunological reaction to a self-antigen/auto-antigen due to dysfunctional control of the immune system (including a loss of tolerance)

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5
Q

What are the 4 types of hypersensitivity reactions?

A

I: immediate/IgE-mediated
II: Ab-dependent
III: Immune complex
IV: Delayed/cell-mediated

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6
Q

What is atopy?

A

Predisposition to allergies in general (e.g. eczema, asthma, hayfever) so often familial/genetic

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7
Q

What are the mediators of type II hypersensitivity reactions?

A

IgM/IgG

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8
Q

What are some examples of type II hypersensitivity reactions?

A

Autoimmune haemolytic anaemia
Goodpasture’s syndrome
Mysasthenia gravis
Graves’ disease

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9
Q

What are the mediators of type III hypersensitivity reactions?

A

Immune complex i.e. Ag-Ab complex

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10
Q

What are some examples of type III hypersensitivity reactions?

A

Serum sickness
Extrinsic allergic alveolitis (EAA)
Rheumatoid arthritis (RA)
Systemic lupus erythematosus (SLE)

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11
Q

What are the mediators of type I hypersensitivity reactions?

A

IgE+ mast cells

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12
Q

What are the mediators of type IV hypersensitivity reactions?

A

T lymphocytes (usually cytotoxic T cell response)

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13
Q

What are some examples of type I hypersensitivity reactions?

A

Allergies (most)
Anaphylaxis
Asthma
Atopy

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14
Q

What are some examples of type IV hypersensitivity reactions?

A

Allergic contact dermatitis
Chronic transplant rejection
Multiple sclerosis (MS)
Tuberculin skin test (TST)

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15
Q

Where are type I hypersensitivity reactions most common?

A

Developed countries

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16
Q

What allergens can cause the various diseases in type I hypersensitivity?

A

Pollen, house dust mites + animal dander -> hayfever + allergic rhinitis

Insect venom, food + drugs -> anaphylaxis usually

Often idiopathic -> asthma + atopic eczema

17
Q

What is the pathology of type I hypersensitivity reactions?

A
  1. First exposure to allergen where crosslinking occurs with B cells
  2. Activation of Th2 cells
  3. Stimulation of IgE class switching of B cells
  4. Production of IgE
  5. Crosslinking of IgE to FceRI on mast cells
  6. Second exposure to allergen will stimulate mast cell degranulation + mediator release (symptoms appear)
18
Q

What mediators are involved in type I hypersensitivity reactions and what types of reactions can these cause?

A

Immediate (mins after 2nd exposure to allergen): vasoactive amines + lipid mediators

Late phase (6-24hrs after 2nd exposure to allergen): cytokines

19
Q

What symptoms does granule exocytosis of mast cells cause in type I hypersensitivity reactions?

A

Vasoactive amines -> vascular dilation + SM contraction

Proteases -> tissue damage

20
Q

What are the symptoms of type I hypersensitivity?

A
Pruritis
Sneezing
Rhinorrhoea 
Lacrimation
Urticaria 
Angioedema
21
Q

What are the symptoms of type I hypersensitivity if the allergen was exposed to the patient systemically?

A
Local swelling
Flushing
Fainting
Dyspnoea
Peri-oral paraesthesia
Throat/chest tightness
Wheeze
Pale
Sweaty
Hypotensive collapse
Unconscious 
Death
22
Q

What is the main difference between type I and type IV hypersensitivity reactions?

A

Type IV are slower + more specific than type I

23
Q

What allergens can cause the various diseases in type IV hypersensitivity?

A

Nickel, metals, formalin + latex -> ACD

24
Q

What are some anomaly examples of type IV hypersensitivity?

A

Chronic organ rejection
Autoimmune e.g. MS
Diagnostic e.g. TST

-> not truly excessive or inappropriate

25
Q

How do you investigate hypersensitivity reactions?

A
  1. Measure blood markers e.g. tryptase, IgE + eosinophil

2. Skin prick testing to identify exact allergen

26
Q

How do you carry out a skin prick test?

A
  1. Apply solution of appropriate test allergens plus -ve & +ve controls (saline + histamine respectively) to skin
  2. Prick through solution into skin + read results after 15 mins
  3. +ve result = lesion > 3mm larger than -ve control
27
Q

What is the difference between a skin prick and skin patch test?

A

More allergens are tested than in the skin prick test + the patient goes away for a week so there is longer contact times

28
Q

What is the main treatment for hypersensitivity reactions?

A

Avoid the allergen

29
Q

What drugs can be used to treat hypersensitivity reactions? How do they work?

A
  1. Mast cell stabilisers (usually topical) -> prevent mast cell degranulation
  2. Anti-histamines (topical/systemic) -> block histamine receptor + effects
  3. Steroids (topical/systemic) -> wide ranging anti-inflammatory effects
  4. LT receptor antagonists (systemic) -> block LT effects
30
Q

What is de-sensitisation treatment?

A

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

31
Q

What is a potential risk of de-sensitisation treatment?

A

Anaphylaxis

32
Q

What treatment do you give for anaphylaxis?

A
  1. Lie patient down
  2. High flow O2
  3. IV fluids
  4. IM adrenaline (EpiPen)
  5. IV chlorphenamine (anti-histamine), IV hydrocortisone (steroid) or nebulised salbutamol (bronchodilator)
  6. Repeat EpiPen if no improvement after 5 mins
33
Q

What is the pneumonic used to remember anaphylaxis treatment?

A

A - airway
B - breathing
C - circulation

34
Q

How should you administer an EpiPen?

A
  1. Form fist around it + pull off grey safety cap
  2. Place back end against out mid-thigh (with/without clothing)
  3. Push down hard until a click is heard/felt + hold in place for 10 seconds
  4. Remove EpiPen + do not touch needle
  5. Massage injection site for 10 seconds
35
Q

What symptoms does enzymatic modification of arachidonic acid in mast cells cause in type I hypersensitivity reactions?

A

Lipid mediators produced:

  • PGs -> vascular dilation
  • LTs -> SM contraction
36
Q

What symptoms does transcriptional activation of cytokine genes in mast cells cause in type I hypersensitivity reactions?

A

Secretion of cytokines e.g. TNF -> inflammation + leukocyte recruitment

37
Q

What are the 3 pathways that get triggered when the allergen binds the mast cell in type I hypersensitivity reactions?

A
  1. Granule with preformed mediator exocytosis
  2. Enzymatic modification of arachidonic acid
  3. Transcriptional activation of cytokine genes