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Year Three - Immunology > Hypersensitivity > Flashcards

Hypersensitivity Flashcards

1
Q

What are hypersensitivity reactions?

A

An overreaction of the immune system to an antigen which would not normally trigger an immune response

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2
Q

What causes tissue damage in hypersensitivity reactions?

A

The tissue damage results from the body’s response to the antigen rather than the damage caused by the antigen itself

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3
Q

Describe the generalised mechanism of hypersensitivity reactions

A

On initial exposure to the antigen, antigen-presenting cells transport the antigen to the nearest lymph node, where it is presented to naïve T-cells

This results in the activation of T-cells and subsequent differentiation into ‘primed’ Th1, Th2 or Th17 cells, which are specific to that antigen and can stimulate further responses if they meet the antigen again

It is the second antigen encounter that could result in a hypersensitivity reaction

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4
Q

What is another term for type I hypersensitivity reactions?

A

Atopy/allergic reactions

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5
Q

What are type I hypersensitivity reactions?

A

There is when IgE antibodies are produced in response to an antigen - referred to as an allergen

It results in mast cell and eosinophil degranulation

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6
Q

Describe the mechanism of type I hypersensitivity reactions

A

On initial exposure to the antigen, there is priming of Th2 cells, and their release of IL-4 causes the B-cells to switch their production of IgM to IgE antibodies

The IgE antibodies bind to Fc receptors on mast cells and eosinophils, which ‘sensitises’ them to the antigen

The mast cells circulate in the body with antigen-specific IgEs attached

When the antigen enters the body again, it cross-links to the IgE antibodies bound to the sensitised mast and basophils cells

This activates the mast cells - resulting in degranulation

The inflammatory mediators are released in the blood and tissues

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7
Q

What three preformed mediators are released during type I hypersensitivity reactions?

A

Histamine

Leukotrienes

Prostaglandins

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8
Q

What are the five clinical features of type I hypersensitivity reactions?

A

Asthma

Rhinitis

Urticaria

Angioedema

Atopic eczema

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9
Q

What do type I hypersensitivity reactions lead to in severe cases?

A

Anaphylaxis

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10
Q

What is anaphylaxis?

A

This is when mediator release leads to systemic bronchoconstriction, vasodilation and increased vascular permeability

This results in a decline in oxygen transportation and blood pressure

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11
Q

What is the investigation used to confirm anaphylaxis following an acute episode?

A

Serum tryptase

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12
Q

What are the two potential complications of anaphylaxis?

A

Anaphylactic shock

Death

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13
Q

What are the two phases of type I hypersensitivity reactions?

A

Immediate Phase

Late Phase

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14
Q

How quickly does the immediate phase of type I hypersensitivity reactions occur?

A

Minutes

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15
Q

What occurs during the immediate phase of type I hypersensitivity reactions?

A

There is release of preformed mediators from basophil and mast cells

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16
Q

How quickly does the late phase of type I hypersensitivity reactions occur?

A

8 - 12 hours

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17
Q

What occurs during the late phase of type I hypersensitivity reactions?

A

This is when the cytokines released from the immediate phase activate basophils, eosinophils and neutrophils

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18
Q

What are the two factors that predispose individuals to type I hypersensitivity reactions?

A

Genetic factors

Environmental factors

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19
Q

What are the two genetic defects that predispose individuals to type I hypersensitivity reactions? How?

A

Filaggrin protein defects

LPS receptors defects

These defects lead to the induction and progressive polarisation of TH2 cells

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20
Q

What is atopy?

A

It refers to the genetic tendency to develop allergic diseases

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21
Q

List six environmental allergens that cause type I hypersensitivity reactions

A

Pollen

Dust mites

Foods

Pets

Insect stings

Medications

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22
Q

What test is used to investigate the allergen causing type I hypersensitivity reactions?

A

Skin-prick testing

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23
Q

How do we conduct a skin-prick test?

A

This test involves placing a drop of various allergen solutions onto the patient’s skin

We then observe for the presentation of skin reactions within 20 – 30 minutes

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24
Q

What is the positive control used in skin-prick tests?

A

Histamine solution

This should become red and swollen with a ‘weal’ in the centre

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25
Q

What is the negative control used in skin-prick tests?

A

Saline solution

This should show no response

26
Q

What are the three treatment options for type I hypersensitivity reactions?

A

Conservative management

Desensitisation therapy

Pharmacological management

27
Q

How do we conservatively manage type I hypersensitivity reactions?

A

It involves advising individuals to avoid the identified allergens

28
Q

What is desensitisation therapy?

A

It involves exposing individuals to small doses of the allergen until they develop tolerance

29
Q

What are the four pharmacological management options for type I hypersensitivity reactions?

A

Beta2 Adrenergic Agonists

Antihistamines

Adrenaline

Corticosteroids

30
Q

What beta 2 adrenergic agonist is used to manage type I hypersensitivity reactions?

A

Salbutamol

31
Q

How are beta 2 adrenergic agonist used to manage type I hypersensitivity reactions?

A

They mimic the effects of the sympathetic nervous system and therefore prevent smooth bronchial muscle contraction

32
Q

What clinical feature of type I hypersensitivity reaction is managed with beta 2 adrenergic agonists?

A

Asthma

33
Q

How are antihistamines used to manage type I hypersensitivity reactions?

A

They block histamine receptors, which are present on mast cells in the skin, nose and mucous membranes

34
Q

What five clinical features of type I hypersensitivity reaction are managed with antihistamines?

A

Rhinitis

Dermatitis

Urticaria

Angioedema

Atopic eczema

35
Q

How is adrenaline used to manage type I hypersensitivity reactions?

A

It stimulates alpha/beta adrenergic receptors to decrease vascular permeability, increase blood pressure and reverse airway obstruction

36
Q

What clinical feature of type I hypersensitivity reaction is managed with adrenaline?

A

Anaphylaxis

37
Q

What is the first line management option during anaphylaxis?

A

Adrenaline

38
Q

In which region of the body should IM adrenaline be injected?

A

Anterolateral aspect of the middle third of the thigh

39
Q

What dose of 1 in 1000 IM adrenaline is used to treat anaphylaxis in 6 month to 6 year old patients?

A

150mcg

40
Q

How are corticosteroids used to manage type I hypersensitivity reactions?

A

They are administered to reduce systemic inflammation during anaphylaxis reactions

41
Q

What are the five immediate management steps of anaphylaxis - in order?

A

Begin ABCDE and ask for senior help

Secure airway + high flow oxygen

IM adrenaline

Secure IV access
IV antihistamine, hydrocortisone, fluids

Nebulised salbutamol

42
Q

After initial emergency treatment of a new diagnosis of anaphylaxis, what is the most appropriate next step?

A

A referral to a specialist allergy clinic

The administration of two adrenaline auto-injections in the interim with training on how to use them

43
Q

What are type II hypersensitivity reactions?

A

They are mediated by IgG or IgM antibodies targeting antigens on host cell surfaces

44
Q

Describe the mechanism of type II hypersensitivity reactions

A

Antibodies binding to cells can activate the complement system, which leads to the degranulation of neutrophils, antibody dependent cell-mediated cytotoxicity (ADCC), opsonisation and formation of the membrane attack complex (MAC)

In addition to this, antibodies can present the antigen to Fc receptor bearing cells, such as T-cells, which can cause cytotoxic action

Ultimately, this results in cell lysis of host cells, leading to tissue-specific damage

45
Q

What is the immune response in type II hypersensitivity reactions?

A

Complement

Macrophages

46
Q

How quickly do type II hypersensitivity reactions occur?

A

Minutes

47
Q

What are the nine clinical examples of type II hypersensitivity reactions?

A

Acute blood transfusion reactions

Hyperacute graft rejection

Autoimmune haemolytic anaemia

Immune thrombocytopenia

Haemolytic disease of the newborn

Grave’s disease

Goodpasture syndrome

Myasthenia gravis

Pemphigus

48
Q

What are type III hypersensitivity reactions?

A

This occur when there is an accumulation of antigen-antibody complexes in the circulation that have not been cleared by the immune system via complement breakdown

These complexes can then be deposited in tissues and cause damage

49
Q

Describe the mechanism of type III hypersensitivity reactions

A

There are impaired immune tolerance mechanisms which allow auto-reactive T cells to recognise self-antigens

This leads to activation of B cells by auto-reactive T cells

IgG antibodies form against and bind self-antigen

Immune complex formation and deposition

Activation of complement and recruitment of inflammatory cells

50
Q

What is the immune response in type III hypersensitivity reactions?

A

Complement system

Neutrophils

51
Q

How quickly do type III hypersensitivity reactions occur?

A

2-24 hours

52
Q

What are the clinical effects of type III hypersensitivity reactions?

A

It results in a local inflammatory response, leading to local swelling, oedema, warmth and redness

53
Q

What are the five clinical examples of type III hypersensitivity reactions?

A

Rheumatoid arthritis

Glomerulonephritis

Vasculitis

SLE

Farmer’s lung

54
Q

How do we manage type III hypersensitivity reactions?

A

Acute - steroids

Chronic - DMARDs (hydroxychloroquine, biologicals)

55
Q

What are type IV hypersensitivity reactions?

A

These reactions are mediated by antigen-specific activated T-cells

56
Q

Describe the mechanism of type IV hypersensitivity reactions

A

When the antigen enters the body, it is processed by APCs and presented together with the MHC II molecule to a Th1 cell

In cases where the Th1 cells has been primed to that specific antigen, it will become activated

This results in the release of chemokines to recruit macrophages and cytokines to activate them

The activated macrophages release pro-inflammatory factors

They also secrete lysosomal elements and reactive oxygen species, which enhances local tissue damage

57
Q

What is the immune response in type IV hypersensitivity reactions?

A

Macrophages

58
Q

How quickly do type IV hypersensitivity reactions occur?

A

2-3 days

59
Q

What are the clinical effects of type IV hypersensitivity reactions?

A

This results in a local inflammatory response, leading to local swelling, oedema, warmth and redness

60
Q

What are the four clinical examples of type IV hypersensitivity reactions?

A

Contact dermatitis

Multiple sclerosis

Type one diabetes

Coeliac disease

Year Three - Immunology (4 decks)

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