(10) Allergic Diseases Flashcards Preview

2. CP - Core Immunology > (10) Allergic Diseases > Flashcards

Flashcards in (10) Allergic Diseases Deck (126):
1

What is allergy/hypersensitivity?

Undesirable, damaging, discomfort-producing and sometimes fatal reactions produced by the normal immune system (directed against innocuous antigens) in a pre-sensitised (immune) host

2

How many immunopathological classifications are there for allergy?

4 types - Coombs and Gell 1963

type 5 - extended classification

3

What are the 4 types of hypersensitivity?

type 1 = anaphylactic

type 2 = cytotoxic

type 3 = immune complex

type 4 = delayed type

4

Which antibodies are involved in the 4 types of hypersensitivity?

type 1 = IgE

type 2 = IgG, IgM

type 3 = IgG, IgM

type 4 = none

5

What is the immunopathogenesis in type II cytotoxic?

IgG/IgM Ab response against combined self/foreign antigen at the cell surface - complement activation/phagocytosis/ADCC

6

What are the clinical features of type II cytotoxic?

- onset minutes to hours
- cell lysis and necrosis

7

What are the common antigens of type II cytotoxic?

Penicillin

8

What are the associated diseases of type II cytotoxic?

- erythroblastosis fetalis
- goodpasture's nephritis

9

What are the steps when penicillin causes a type II cytotoxic reaction to cause lysis?

- complement-coated penicillin-modified red blood cells are phagocytosed by macrophages using their complement receptors
- macrophages present peptides from the penicillin-protein conjugate and activate specific CD4 T cells to become TH2 cells
- B cells are activated by the antigen and by help from activated TH2 cells
- Plasma cells secrete penicillin-specific IgG which binds to modified red blood cells
- complement lytic pathway

10

What is the immunopathology in type III-immune complex reactions?

IgG/IgM Ab against soluble antigen-immune complex deposition

11

What are the clinical features of type III-immune complex reactions?

- onset 3-8 hours
- vasculitis

12

What is the traditional cause of type III-immune complex reactions?

Serum sickness

Mouldy hay – farmer’s lung

13

What disease is associated with type III-immune complex reaction?

SLE

14

If the site of immune-complex deposition is the blood vessel walls, what is the resulting disease?

Vasculitis

15

If the site of immune-complex deposition is the renal glomeruli, what is the resulting disease?

Nephritis

16

If the site of immune-complex deposition is the joint spaces, what is the resulting disease?

Arthritis

17

If the site of immune-complex deposition is the perivascular area, what is the resulting disease?

Arthus reaction

18

What is arthus reaction?

The Arthus reaction is a type of local type III hypersensitivity reaction which involves the deposition of antigen/antibody complexes mainly in the vascular walls, serosa (pleura, pericardium, synovium) and glomeruli.

19

If the site of the immune-complex deposition is the alveolar/capillary interface, what is the resulting disease?

Farmer’s lung

20

What is the immunopathology in type IV-delayed reactions?

Antigen specific T-cell mediated cytotoxicity

21

What are the clinical features of type IV-delayed reactions?

- delayed onset 48-72 hours
- erythema induration

22

What is the common antigen in type IV-delayed reactions?

- metals eg. Nickel
- (tuberculin reaction)

23

What disease is associated with type IV-delayed allergic reaction?

Contact dermatitis

24

In type IV-delayed allergic reactions, an antigen leads to a T cell response, briefly describe the following steps

- antigen is processed by tissue macrophages and stimulates THI cells
- chemokines, cytokines and cytotoxins are released which perform different functions

25

In type IV-delayed allergic reactions, chemokines, cytokines and cytotoxins are released. State which and their functions

- chemokines = macrophage recruitment to the site of antigen
- IFN-y = activates macrophages increasing release of inflammatory mediators
- TNF-a and TNF-b = local tissue destruction, increased expression of adhesion molecules on local blood vessels
- IL-3/GM-CSF = monocyte production by bone marrow stem cells

26

Describe the stages in the development of allergy

- environment and genetics (atopy)
- barrier dysfunction
- sensitisation
- changes in T cell sub-sets dominated by Th2
- IgE
- ALLERGY

27

Which allergy is associated with the eyes?

Allergic conjunctivitis

28

Which allergy is associated with the nose?

Allergic rhinitis

29

Which allergy is associated with the mouth?

Oral allergy syndrome

30

Which allergy is associated with the airways?

Allergic asthma

31

Which allergy is associated with the skin?

Atopic dermatitis

32

Which allergy is associated with the GI tract?

Food allergy

33

How do we get allergies?

- those components of the immune system involved in responses to parasitic infection are also involved in allergic responses
- the system has developed to produce a rapid tissue-based response to re-infection
- the lack of infectious drive is a contributory factor in allergic disease

34

In immune response to parasitic disease, what is there increased levels of?

Increased levels of IgE
- total
- specific to pathogen – cross-reactive

35

In immune responses to parasitic diseases, there is tissue inflammation with what?

- eosinophilia and mastocytosis
- basophil infiltration

36

What is eosinophilia?

An increase in the number of eosinophils in the blood, occurring in response to some allergens, drugs, and parasites, and in some types of leukaemia

37

Which cells are present in immune responses to parasitic disease?

Presence of CD4+ T cells secreting: IL4, IL5, IL13

38

Describe the ‘hygiene hypothesis’ in relation to parasitic disease and allergy

- stimulation by microbes is protective
- animal models – T1DM, EAE, asthma
- increased atopy (asthma) after anti-parasitic Rx
- prevention of autoimmunity (Crohn’s) by infections
- pro-biotics in pregnant women
- mechanism – Th1 Th2 deviation

39

What are the genetic influences on the ‘allergic’ immune response?

- polygenic disease
- cytokine gene cluster IL3, IL, IL9, IL13
- IL12R; IL4R
- FceRI
- IFNg; TNF

40

Are genetic influences of ‘allergic’ immune response sufficient for disease?

No, not sufficient for disease, only susceptibility

41

What defects causing an allergic response can be caused by genes?

- barrier function
- tissue response
- atopic immune responses
- environment sensing
- eosinophils

42

Which genes contribute to all of asthma, atopic dermatitis and allergic rhinitis?

C11orf30
LRRC32

43

Which genes contribute to only allergic rhinitis?

TLR6
NOD1

44

Which gene contributes to both asthma and allergic rhinitis?

TSLP

45

What is an allergen?

Antigens that initiate an IgE-mediated response

46

What does the first encounter with an allergen result in?

Innate and IgM response (you do not generate and allergic response on first encounter)

47

What is the conventional immune response?

- allergen requires processing
- presentation to T cells and cytokine release
- results in delineation of T-helper subsets into different types

48

In allergic responses, what are the early priming events?

- decreased barrier function
- allergen is passively taken in or actively taken up through barrier
- immature dendritic cell gets activated
- dendritic cell migrates and matures
- mature dendritic cell presents antigen to naive T cell in lymph node
- T cell activation
- Th2-cell development

49

What is a dendritic cell?

Antigen-presenting cell

Main function is to process antigen material and present it on the cell surface to T cells

50

In an allergic response there is differentiation of T-helper cells. Give 4 different types of T helper cell involved

- Th1
- Th2
- Th17
- Treg

51

What do Treg cells do?

Regulatory T cells calm down the immune response. They cause inflammatory suppression caused by the other T helper cells

52

Which effector cytokines do Treg cells release?

- IL-10
- TGFb

53

Which effector cytokines do Th1 cells release?

- IFN-y
- IL-2

54

Which effector cytokines do Th2 cells release?

- IL-4
- IL-5
- IL-13

55

Which effector cytokines do Th17 cells release?

- IL-17
- IL-21
- IL-22

56

How are IgE antibodies produced?

Th2 cells release IL-4 cytokines which stimulates the B cells to proliferate and produce IgE

57

Which cell is ultimately responsible for IgE production?

B cells

58

Which T cell is involved in IgE production?

Th2

59

Which cytokines is involved in IgE production?

IL-4

60

How do IgE antibodies go on to produce an allergic response? (type I allergic response)

- IgE binds to the Fc receptor on sensitised mast cells
- mast cells activation and degranulation
- release of mediators which cause the symptoms

61

Which parts of the body are affected by the vasoactive amines/lipid mediators/chemokines/cytokines released by mast cells and basophils?

- smooth muscle
- blood vessels
- platelets
- sensory nerve endings
- eosinophils

62

What is the immunopathogenesis in IgE mediated allergic response?

IgE antibody mediated mast cell and basophil degranulation - release of pre-formed and de novo synthesised inflammatory mediators

63

What are the clinical features of IgE mediated allergic response?

- fast onset (15-30 minutes)
- wheal and flare

(unlikely to be this allergy if presents the day after)

64

What are the two types of response in IgE mediated allergic responses?

1. initial response/immediate phase
2. late-phase reaction

65

What is involved in the initial response in IgE mediated allergic responses?

- degranulation of mast cells and basophils
- granule contents = histamine, proteases, chemotactic factors

(primary mediators)

66

What is involved in the late-phase reaction in IgE-mediated allergic responses?

Arachidonic pathway

- secondary mediators
- leukotrienes and prostaglandins

- eosinophils
- central role for Th2 T cell

67

What is the role of the Th2 T cell?

- multiple cytokine release
- innate inflammatory response (macrophages etc)
- drive for immunoglobin production (support for B cells)

68

What are the 3 conditions in the atopic triad?

- asthma
- rhinitis
- eczema

69

Which of the atopic triad are type I hypersensitivity?

- asthma
- rhinitis

70

Which of the atopic triad are type IV hypersensitivity?

- eczema

71

What are the symptoms of allergic rhinitis caused by mast cells in the nasal mucosa and airway epithelium?

- nasal congestion (oedema, mucus, nasal polyps)
- nasal inflammation
- tonsillar and adenoidal enlargement

72

What are the symptoms of asthma caused by mast cells in the airway epithelium and lungs?

- airway inflammation (oedema, mucus)
- airway constriction and hyper-reactivity

73

What are the two types of rhinitis?

- allergic
- non-allergic

74

What are the two types of allergic rhinitis?

- perennial
- seasonal

75

What allergens can cause rhinits?

- house dust mite
- animal danders
- pollens

76

What are the symptoms of rhinitis?

- blocked nose
- runny nose
- often with eye symptoms

77

What is the treatment for rhinitis?

- antihistamines
- nasal steroids

78

What is asthma a disease of?

Inflammation and hyper-reactivity of the small airways

79

Which allergens cause asthma?

- aero-allergic stimuli in childhood (airborne allergens)
- house dust mite - key pathogenic importance

80

What are the immediate symptoms of asthma due to?

IgE mediated

81

What is damage to the airways in asthma caused by?

Late phase reaction

82

Damaged airways in asthma are hyper-reactive to what?

Non-allergic stimuli eg. fumes

83

What is the basic difference between asthma and rhinitis?

Rhinitis = upper airways
Asthma = lower airways

84

What is the pathogenesis in asthma? (describe the inflammatory cascade in allergic asthma)

- allergen
- antigen-presenting cell
- Th2 cell
- IL-4 and IL-3 to B cell plasma cell
- IL-5 to eosinophil
- B cell plasma cells produces IgE
- IgE to mast cells and basophils
- mast cells, basophils and eosinophils cause release of histamine, leukotrienes, prostaglandins, cytokines, basic proteins and enzymes
- allergic asthma

85

What are the two major types of dermatitis?

- atopic
- contact (allergic/non-allergic)

86

What is atopic dermatitis also known as?

Atopic eczema

87

How would a patient with atopic dermatitis present?

- intense itching
- blistering/weeping
- cracking of skin

88

What is a major trigger in atopic dermatitis?

House dust mite

89

What is the treatment for atopic dermatitis?

- topical steroids
- moisturisers

90

Which cytokine mediator causes the scratch/pruritus in atopic dermatitis?

IL-31 directly causes scratch

91

How is there a viscous circle in atopic dermatitis?

Barrier disruption leads to development of Th2 then IgE and also T cell-derived itch mediator: IL-31

This causes pruritus/scratch

The scratching causes further barrier disruption and therefore more IL-31 and more scratching

92

What is anaphylaxis?

An acute, potentially life-threatening, IgE-mediated systemic hypersensitivity reaction

93

What are the 3 classifications of anaphylaxis?

- 1 (mild)
- 2 (moderate)
- 3 (severe)

94

What are some symptoms of type 1 (mild) anaphylaxis?

- pruritus
- abdominal pain
- nausea and vomiting
- runny nose and sneezing
- throat tightness
- mild wheezing
- tachycardia (>15 beats per min)
- increased anxiety

95

What are some symptoms of type 2 (moderate) anaphylaxis?

- angioedema
- severe abdominal pain
- dysphagia
- hoarseness
- moderate dyspnoea
- tachycardia (>15 beats per min)
- light-headedness
- feel of pending life-threatening event

96

What are some symptoms of type 3 (severe) anaphylaxis?

- profuse diarrhoea and loss of bowel control
- severe wheezing
- sao2

97

What are the methods of diagnosis of allergy?

- history
- specific IgE (>0.35 KuA/L)
- skin prick test (>3mm wheal)
- intra-dermal test
- oral challenge test
- basophil activation test
- component resolved diagnostics

98

What is the gold standard test in allergy diagnosis?

Oral challenge test

eg. feed peanut and see what happens (quick onset)

99

Why is history important in allergy diagnosis?

Temporal relationship between exposure and symptoms is relevant

Type 1 = symptoms are short-lived

100

How do you measure IgE in allergy diagnosis?

Blood sample

BUT can have positive test and be clinically tolerant

101

How is a skin prick test carried out in allergy diagnosis?

EG.

negative control = drop of saline solution on skin

positive control = drop of histamine on skin

then eg. drop of grass pollen on skin

and see if you have a reaction

102

What happens in chronic spontaneous urticaria?

Random rashes for no reason

103

How does the basophil activation test work in allergy diagnosis?

Certain substances (makers) inside the basophil cell either come out of the cell or increase in number when the cell is activated

eg. CD63 comes out of the cell

104

What are the advantages and disadvantages of the specific IgE test in allergy diagnosis?

Advantage = safe (just a blood test)

Disadvantage = false negatives and false positives

105

What are advantages and disadvantages of the skin prick test in allergy diagnosis?

Advantage = quick (don't have to send samples to lab) and patient satisfaction

Disadvantages = false negatives, false positives, antihistamines, slight risk

106

What are the symptomatic treatments for allergy?

- antihistamines
- steroids
- adrenaline

107

What specific treatment is there for allergy?

Immunotherapy - modulate immune system (subcutaneous or sublingual administration)

108

What are the indications for immunotherapy for allergy?

- life threatening reactions to wasp and bee sting
- severe hay fever
- animal dander allergy

109

Immunotherapy for allergy is not helpful in which situations?

- multiple allergies
- food allergy
- allergic rashed eg. eczema, urticaria

110

Describe the mechanism of immunotherapy

- more Th1 and less Th2 in tissues
- decreased IgE and more of other types of antibodies (IgG, IgA) and so more competition

111

What are the major food allergens?

- cow's milk
- egg
- legumes (peanut, soybean, tree nuts)
- fish
- crustaceans/molluscs
- cereal grains

112

The major food allergens are what type of proteins?

Water-soluble glycoproteins 10-60kd

113

What are the clinical manifestations of food allergy?

Gastrointestinal
- vomiting
- diarrhoea
- oral symptoms

Respiratory (upper and lower)
- rhinitis
- bronchospasm

Cutaneous
- urticaria
- angioedema
- role of food in atopic dermatitis is unclear

Anaphylaxis

114

Food allergy can be of which 3 types?

- IgE-mediated
- non-IgE mediated
- mixed

115

What are some examples of causative agents of IgE mediated type I drug allergy?

- B-lactam antibiotics
- platinum-based chemotherapeutics
- perioperative agents

116

What are the clinical manifestations of IgE mediated type I drug allergy?

- urticaria
- angioedema
- bronchospasm
- anaphylaxis

117

What are some examples of causative agents of cytotoxic type II drug allergy?

- penicillin
- quinine
- sulfonamides

118

What are the clinical manifestations of cytotoxic type II drug allergy?

- haemolytic anaemia
- thombocytopenia
- granulocytopenia

119

What are some examples of causative agents of immune complex type III drug allergy?

- penicillin
- infliximab
- thymoglobulin

120

What are the clinical manifestations of immune complex type III drug allergy?

- serum sickness

121

What are some examples causative agents of delayed type type IV drug allergy?

- neomycin
- glucocorticoids
- penicillin
- sulfonamide antibiotics

122

What are the clinical manifestations of delayed type type IV drug allergy?

- contact dermatitis
- exanthems

123

What are the response times in the 4 different types of hypersensitivity?

type I anaphylactic = 15-30 minutes

type II cytotoxic = minutes-hours

type III immune complex = 3-8 hours

type IV = 48-72 hours

124

What is the appearance of the 4 different types of hypersensitivity?

type I anaphylactic = wheal and flare

type II cytotoxic = lysis and necrosis

type III immune complex = erythema, oedema, necrosis

type IV delayed type = erythema induration

125

What is the histology of the 4 different types of hypersensitivity?

type I anaphylactic = basophils and eosinophils

type II cytotoxic = antibody and complement

type III immune complex = complement and neutrophils

type IV delayed type = monocytes and lymphocytes

126

What type of antigens are involved in the 4 different types of hypersensitivity?

type I anaphylactic = exogenous

type II cytotoxic = cell surface

type III immune complex = soluble

type IV delayed type = tissues and organs