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Y2 Clinical Pathology > Allergic Disease > Flashcards

Allergic Disease Flashcards

1
Q

What is the definition of an allergic reaction?

A

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

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2
Q

What is meant by “innocuous antigens” and “pre-sensitised host”?

A

Innocuous antigens:

  • this is an antigen that is not usually harmful

Pre-sensitised host:

  • the host has had prior exposure to the innocuous antigen
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3
Q

What are the 4 types of hypersensitivity?

A

Type I - anaphylactic

Type II - cytotoxic

Type III - immune complex

Type IV - delayed type

Types I, II and III are mediated by antibodies

Type IV is a mediated by cells

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4
Q

What are the characteristics of a type I (anaphylactic) allergic reaction?

A
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5
Q

What are the characteristics of a type II (cytotoxic) reaction?

A
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6
Q

What are the characteristics of a type III (immune complex) reaction?

A
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7
Q

What are the characteristics of a type IV (delayed type) reaction?

A
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8
Q

What is the immunopathogenesis of a type II (cytotoxic) reaction?

A
  • It is an IgG/IgM antibody response against combined self/foreign antigen at the cell surface
  • the antigens are on the cell surface
  • this leads to complement activation/phagocytosis/ADCC
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9
Q

What are the clinical features and common antigens associated with a type II cytotoxic allergic reaction?

A

Clinical features:

  • onset of minutes to hours
  • cell lysis and necrosis

Common antigens:

  • penicillin
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10
Q

What diseases are associated with a type II hypersensitivity reaction?

A
  • Erythroblastosis fetalis
  • goodpasture’s nephritis
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11
Q

How does haemolytic disease of the newborn work?

A
  1. IgG molecules produced by the mother pass through the placenta
  2. Some antibodies attack antigens on the surface of red blood cells in the foetal circulation
  3. The foetus then develops reticulocytosis and anaemia
  4. Many erythroblasts are present in the fetal blood
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12
Q

What is the immunopathology of type III hypersensitivity reactions like?

A

IgG/IgM antibodies against soluble antigens

this leads to immune complex deposition in the skin, kidneys and joints

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13
Q

What are the clinical features and associated diseases of Type III hypersensitivity reactions?

A

Clinical features:

  • onset of 3 - 8 hours
  • vasculitis

Associated diseases:

  • the traditional cause is serum sickness
  • SLE
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14
Q

What is meant by serum sickness?

A

A reaction to proteins in antiserum derived from a non-human animal source occurring 5-10 days after exposure

The immune system mistakes the proteins for harmful antigens

the body produces antibodies which combine with the proteins to form immune complexes

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15
Q

What happens to the immune complexes after they have formed?

A

The complexes precipitate and enter the walls of blood vessels to activate the complement cascade

they initiate an inflammatory response

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16
Q

What are the typical symptoms of serum sickness?

A

rashes

itching

joint pain (arthralgia), especially finger and toe joints

fever, as high as 40 °C and usually appears before rash

lymphadenopathy (swelling of lymph nodes), particularly near the site of injection, head and neck

malaise

hypotension (decreased blood pressure)

splenomegaly (enlarged spleen)

glomerulonephritis

protein in the urine

blood in the urine

shock

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17
Q

Complete the table with the route of antiserum administration and the site of immune complex deposition

A
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18
Q

What is the immunopathology and clinical features of a type IV hypersensitivity reaction?

A

Immunopathology:

  • antigen specific T-cell mediated cytotoxicity

Clinical features:

  • delayed onset of 48-72 hours
  • erythema and induration
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19
Q

What are the common causes and associated diseases associated with Type IV hypersensitivity?

A

Common causes:

  • metals e.g. nickel
  • tuberculin reaction

Associated diseases:

  • contact dermatitis
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20
Q

What is the mechanism behind a Type IV hypersensitivity reaction?

A
  1. CD4+ Th1 cells recognise foreign antigen in a complex with the MHC class II on the surface of APCs
  2. The T cells are drivers of pathology that secrete chemokines and cytokines that cause damage
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21
Q

What cytokines and chemokines are secreted as part of the Type IV delayed response?

A
  • Macrophages secrete IL-12, which stimulates the proliferation of further Th1 cells
  • T cells secrete Il-2 and IFN-gamma, which induces further release of other Th1 cytokines
  • Activated CD8+ T cells destroy target cells on contact, whilst activated macrophages produce hydrolytic enzymes
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22
Q

What is the end result of the type IV hypersensitivity reaction?

A

Overreaction of helper T cells and overproduction of cytokines damages tissues, causes inflammation and cell death

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23
Q

Why do people get allergies?

A
  • The components of the immune system involved in allergic responses are primarily involved in responses to parasitic infection
  • the immune system has evolved to generate a rapid tissue-based response to reinfection
  • the lack of infectious drive is also a contributatory factor
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24
Q

What characteristics of the immune response to parasitic disease is the same in an allergic reaction?

A

Increased levels of IgE:

  • both total and cross-reactive (specific to pathogen)

Tissue inflammation with:

  • eosinophils and mast cells
  • basophil infiltration

Presence of CD4+ T cells secreting:

  • IL4, IL5 and IL13
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25
Q

What is meant by the ‘hygiene hypothesis’?

A

Immune stimulation by microbes protects against allergies

If the immune system is not fighting against bacteria, it turns to fight against the harmless antigens

A pathogen-free environment leads to increased incidence of disease

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26
Q

What is the mechanism behind the hygiene hypothesis?

A
  • There is deviation from a Th1 response to a Th2 response
  • there is lack of antigenic competition from infections, which leads to immune regulation
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27
Q

What is meant by the genetic influences on the allergic immune response?

What is significant about the genetic component?

A

Only involves polygenic diseases

cytokine gene cluster IL3, 5, 9, 13

IL12R, IL4R

FceRI

IFN-gamma and TNF

These are NOT sufficient for disease, only susceptibility

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28
Q

What are the 4 groups of susceptibility genes for allergic diseases?

A
  1. Environment sensing genes
  2. Atopic immune responses
  3. Tissue response genes
  4. Barrier function genes
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29
Q

What is meant by ‘environment setting’ genes?

A

They encode molecules that directly modulate the effect of environmental risk factors for allergic disease

e.g. Modulate the effect of exposures involving tobacco smoke and air pollution on asthma susceptibility

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30
Q

What is meant by barrier function genes?

A

They tend to be expressed in the epithelium

they affect epithelial and dermal barrier function, allowing the allergen to enter the body more easily

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31
Q

What is meant by the genes that regulate atopic inflammation?

A

They regulate Th1/Th2 differentiation and effector function

they regulate atopic sensitisation

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32
Q

What is meant by ‘atopy’?

A

personal and/or familial tendency to become sensitised and produce IgE antibodies in response to ordinary exposure to allergens, usually proteins

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33
Q

What is meant by tissue response genes?

A

Genes that modulate the consequences of chronic inflammation

34
Q

What are the stages involved in development of allergy?

A
35
Q

What is meant by ‘sensitisation’?

A

The process by which a person’s body becomes sensitive to a particular allergen

someone must have encountered an antigen at least once before in order to become allergic to it

36
Q

What are the stages in the conventional immune response?

A
  1. Antigen requires processing
  2. Presentation to T cells and cytokine release
  3. This results in delineation of T-helper subsets into different types
37
Q

What is different about an alllergic response compared to the conventional immune response?

A
  1. Antigens initiate an IgE-mediated response
  2. First encounter results in innate and IgM response
38
Q

What are the stages of IgE production shown in the diagram?

A
  1. Allergen is recognised by B cell and Th2 cell
  2. Th2 cell produces IL-4, which causes the B cells to proliferate
  3. B cells differentiate into plasma cells and produce antibodies
39
Q

What must happen in order for the allergen to enter the bloodstream?

A

The barrier function must be disrupted due to inflammation or genetic defect

the allergen then enters regional lymph nodes where it is presented to T cells via an APC

40
Q

What cytokines determine what type of T cell the naive CD4+ T cell will differentiate into?

A
41
Q

What effector cytokines are produced by the different types of T cell?

A
42
Q

What are the 3 main roles of the Th2 T cell?

A
  1. Multiple cytokine release
  2. Part of the innate inflammatory response
  3. Drive for immunoglobulin production
43
Q

What are the stages involved in the Type I allergic response?

A
  1. Allergen is recognised by both the B and T cell
  2. IL-4 produced by T cell signals to the B cell to proliferate, differentiate into plasma cells and produce antibodies
  3. IgE antibodies attach to mast cells
  4. The allergen crosslinks antibodies on the surface of the sensitised mast cell
  5. This causes degranulation of the mast cell and release of vasoactive amines
44
Q

What is the immunopathogenesis of the IgE mediated allergic response?

A
  • IgE mediated mast cell and basophil degranulation
  • leads to the release of preformed and de novo synthesised inflammatory mediators
45
Q

What are the clinical features of the IgE mediated allergic response and late phase response?

A

Clinical features:

  • fast onset (15-30 mins)
  • wheal and flare

Late phase response:

  • involves eosinophils
  • central role for Th2 T cell
46
Q

What are the main primary mediators of the IgE mediated allergic reaction?

A
  1. Histamine
  2. Proteases
  3. Chemotactic factors

these primary mediators are involved in the initial response

47
Q

What are the main secondary mediators involved in the IgE-mediated allergic reaction?

A
  1. Leukotrienes
  2. Prostaglandin D2

these secondary mediators are involved in the late phase reaction

48
Q

What is meant by anaphylaxis?

A

serious allergic reaction that is rapid in onset and may cause death

49
Q

What are the 3 ways to define anaphylaxis?

A

Definition 1:

  • sudden onset of illness with involvement of the skin, mucosal tissue or both
  • and at least one of:
  1. Sudden respiratory symptoms
  2. sudden reduced BP or symptoms of end-organ dysfunction

Definition 2:

  • two or more of the following that occur suddenly after exposure to a likely allergen:
  1. sudden skin or mucosal symptoms and signs
  2. sudden respiratory symptoms
  3. sudden reduced BP or symptoms of end organ dysfunction
  4. sudden gastrointestinal symptoms

Definition 3:

  • reduced BP after exposure to a known allergen for that patient
50
Q

What is meant by the atopic triad?

A
  1. Asthma
  2. Rhinitis
  3. Eczema
51
Q

What are the typical symptoms of allergic rhinitis and asthma?

A

Allergic rhinitis:

  • nasal congestion
  • nasal inflammation
  • tonsillar and adenoidal enlargement

Asthma:

  • airway inflammation
  • airway constriction and hyperreactivity
  • obstructive sleep apnoea
  • decreased nasopharyngeal area
52
Q

What are the typical symptoms of rhinitis?

A
  1. Blocked/runny/itchy nose
  2. Sneezing
  3. Conjunctivitis symptoms - itching/burning/watering eyes
53
Q

Complete the diagram demonstrating the 2 types of rhinitis?

A
54
Q

What are the characteristics of asthma?

What is significant about asthma in childhood?

A

It is a disease of inflammation and hyper-reactivity of the small airways

in childhood, aero-allergic stimuli such as the house dust-mite are of pathogenic importance

there is more of an allergic component in childhood asthma

55
Q

What causes symptoms and airway damage in asthma?

A

Immediate symptoms are IgE-mediated

Damage to the airways is due to the late phase response

Damage airways are hyper-reactive to non-allergic stimuli e.g. fumes

56
Q

What is involved in the pathogenesis of asthma?

A
57
Q

Complete the diagram of dermatitis classification

A
58
Q

What are the clinical features of dermatitis?

A

Intense itching, blistering/weeping, cracking of skin

house dust mite is a major trigger in atopic disease

59
Q

What is the treatment for rhinitis?

A

Antihistamines and intranasal steroids

60
Q

What is the treatment for dermatitis?

A

Topical steroids and moisturisers

61
Q

What is meant by pruitis?

What is its role in the allergy?

A

An unpleasant sensation of the skin which provokes the urge to scratch

itching increases barrier disruption, allowing the allergen to get into the body

62
Q

What is a ‘hapten’?

A

a small molecule which, when combined with a larger carrier such as a protein, can elicit the production of antibodies which bind specifically to it

63
Q

What tests are used in the diagnosis of an allergy?

A
  1. Specific IgE
  2. Skin prick test
  3. Intra-dermal test
  4. Graded challenge test
  5. Basophil activation test
  6. Component resolved diagnostics
64
Q

What is meant by the specific IgE measurement?

A

Measure the amount of IgE in the blood

>0.35 KuA/L is a positive result

a negative test doesn’t always exclude allergy as the IgE antibodies can be stuck to the surface of cells and not in the bloodstream

65
Q

What is meant by the skin prick test?

A

Drops of allergens are placed on the skin and then the skin surface is scratched

histamine is a positive control as it will generate a response

saline is used as a negative control (as some patients have sensitive skin)

a lancet is used to scratch the skin and see if one of the allergens causes a reaction

66
Q

What is a positive skin prick test result?

A

Wheal and erythema

wheal is a small lump and it is positive test if it is more than 2mm larger than the negative control

67
Q

What is the intra-dermal test?

A

A tiny amount of allergen is injected into the skin and a pen line is drawn around the site of injection

after 10-15 mins, note the size of the site of injection

if the size increases by 3mm or more then the test is positive

68
Q

What is meant by the basophil activation test?

A

A blood sample is taken and antigen is added externally

if a specific antibody is stuck on the basophil, molecules project out onto the surface from below

69
Q

What are advantages and disadvantages of specific IgE testing?

A

Advantages:

  • very safe

Disadvantages:

  • false negatives if antigens are on cell surface and not in blood stream
  • and false positives in asthma and eczema patients with high levels of IgE
70
Q

What are the positives and negatives of a skin prick test?

A

Positives:

  • quick
  • patient satisfaction

Negatives:

  • false negatives if patients are taking anti-histamines
  • false positives in patients with sensitive skin
  • slight risk of triggering reaction
71
Q

What are the treatments for allergic reactions?

A

Antihistamines, steroids, adrenaline

or

subcutaenous/sublingual immunotherapy

72
Q

What are the indications for use of immunotherapy?

A
  • Life threatening reactions to wasp and bee stings
  • severe hay fever
  • animal dander allergy

It is not useful in:

  • multiple allergies
  • food allergy
  • eczema
  • spontaenous urticaria
73
Q

Why is immunotherapy used?

A

It improves quality of life of treated individuals and has been shown to reduce both symptoms of allergy and medication use

74
Q

How does immunotherapy work?

A
  1. It modifies cellular and humoral responses to allergens
  2. Ratio of Th1 cytokines to Th2 cytokines is increased
  3. Regulatory T cells are induced

This works for around 5-8 years and then the patient develops the allergy again

75
Q

What is the difference between food intolerance and food allergy?

A

Food intolerance:

  • this is NOT related to IgE mediated reactions
  • it includes things like palpitations due to caffeine intake and lactose intolerance due to absent enzymes

Food allergy:

  • this involves both IgE and non-IgE mediated reactions
76
Q

Complete the table for food allergy and intolerances

A
77
Q

What are the 6 major food allergens?

A

They are water soluble glycoproteins 10-60 kd

  1. Cow’s milk
  2. Egg
  3. Legumes - peanut, soybean, tree nuts
  4. Fish
  5. Crustaceans/molluscs
  6. Cereal grains
78
Q

What are the 3 systems affected by adverse reactions to food?

A

Gastrointestinal:

  • vomiting, diarrhoea and oral symptoms

Respiratory (upper and lower):

  • rhinitis, bronchospasm

Cutaneous:

  • urticaria, angioedema
  • role of food in atopic dermatitis unclear

anaphylaxis

79
Q

How are reactions to drugs tested for?

A

IgE mediated reactions are the only ones that can be tested for

Penicillin can cause all 4 types of hypersensitivity reactions

80
Q

What aspects should be considered in taking a history for drug allergy?

A
  1. Indication for the drug
  2. Detailed description of the reaction
  3. Time between drug intake and onset of symptoms
  4. Number of doses taken before onset
  5. Aware of pharmacological effects and non-immunological ADR
81
Q

What are the stages in management of drug allergy?

A
  1. Intradermal testing
  2. Graded challenge
  3. Desensitisation

Y2 Clinical Pathology (76 decks)

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