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4 - Y5 a Path lectures 2021/22 > ** Immuno 3: Allergy > Flashcards

** Immuno 3: Allergy Flashcards

1
Q

What is an allergic disorder

A

immunological process that results in immediate and reproducible symptoms after exposure to an allergen
o Usually involves an IgE-mediated type 1 hypersensitivity reaction

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2
Q

What is an allergen

A

usually a harmless substance that can trigger an IgE-mediated immune response and may result in clinical symptoms

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3
Q

What is sensitisation

A

detection of specific IgE either by skin prick testing or in vivo blood tests
o NOTE: this shows risk of allergic disorder but does not define allergic disease

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4
Q

What is the difference in immune responses to microbes vs helminths/allergens/venoms?

A
  • Pathogens have conserved structures that can be recognised by cells of the immune system (Th1 and Th17)
  • Multicellular organisms and allergens don’t necessarily have conserved structures that are recognised by immune cells, instead they release mediators (e.g. proteases) that disturb epithelial barriers which is a functional change that is recognised by the immune system and gives rise to Th2-mediated responses
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5
Q

What are the 2 types of immune response to an allergen?

A
  • Th2
  • mast cell
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6
Q

give an Overview of the Th2 Immune Response

A
  • Stressed or damaged epithelium will release signalling cytokines (e.g. TSLP)
  • These cytokines will act on Th2 cells, Th9 cells and ILC2 cells and promote the section of IL4, IL5 and IL13
  • These then act on eosinophils and basophils which plays a role in the expulsion of parasites and allergens but can also contribute to tissue injury
  • The TSLP and other cytokines released by the damaged epithelium can also activate follicular Th2 cells which then releases IL4
  • IL4 stimulates B cells to produce IgE and IgG4
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7
Q

give an Overview of the mast cell Immune Response

A
  • In another form of allergic response, the sensor is the mast cell
  • The allergen will cause cross-linking of IgE giving rise to the release of histamine, prostaglandins and leukotrienes
  • These mediates act on the endothelium causing increased permeability, the smooth muscle (contract) and neurones (to cause an itch)
  • This response will expel the parasite/allergen or it will be responsible for the symptoms of asthma, eczema and hayfever
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8
Q

Where are innate lymphoid cells found? What is special about them?

A
  • Innate lymphoid cells found at mucosal barriers (skin, respiratory and the gastrointestinal tract)
  • lack antigen specific receptors
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9
Q

What do innate lymphoid cells respond to?

A
  • Respond to a number of inflammatory cytokines:
    • (IL-33, TSLP, IL-25)
    • IL-1 family cytokines members
    • IL-12 family cytokines members
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10
Q

How are CD4 innate lymphoid cells classified?

A
  • CD4 innate lymphoid cells (ILC) classified into ILC1, ILC2, ILC3,
  • based on their cytokine production & transcriptional profiles
  • ILC1s, ILC2s, and ILC3s resembling CD4+ T helper (Th)1, Th2 and Th17/22 cells, respectively
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11
Q

What do innate lymphoid cells (ILC) secrete? What is the significance of this?

A
  • ILC2 secrete IL-4, IL-5, IL-9, IL-13 & amphiregulin (AREG)
    • Secretion of the above type 2 cytokines is implicated in allergic asthma, allergic rhinitis AD, food allergy & eosinophilic oesophagitis
    • Amphiregulin plays an important role in epithelial barrier repair in skin & respiratory tract
    • In allergic disease the above secretion overcomes steady state inhibition exerted by tissue CD4 T regulatory cells
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12
Q

What are CD4 Th2 cells?

What do they secrete?

What are their actions?

A

Distinct CD4 T subset characterised by expression of the lineage determining transcription factor GATA-3 and the signal transduction protein STAT-6

Secrete:

  • Signature cytokines are IL-4, IL-5, IL-13

Actions:

  • Helps B cells to produce IgE (IL-4)
  • Expands and activate eosinophils (IL-5)
  • Stimulate mucous secretion (IL-13)
  • Role in host defense against helminths, parasites and tissue repair
  • Contribute to late stage tissue damage in allergic disease
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13
Q

What is the process of Induction of Th2 Immune Responses

A
  • Not well understood
  • The primary defect is thought to be in the epithelial barrier
    • E.g. skin defect is a significant risk factor for the development of IgE antibodies (atopic dermatitis)
  • Skin dendritic cells (Langerhans cells and dermal dendritic cells) promote secretion of Th2 cytokines much more efficiently than other dendritic cell subtypes
  • This suggests that different dendritic cell subsets will prime the Th2 immune responses in humans to different levels
  • IL4 secretion is only induced by peptide-MHC presentation to TCR or naïve/memory Th2 cells
  • TAKE HOME MESSAGE: oral exposure promotes immune tolerance (TOP in pic) whereas skin and respiratory exposure induces IgE sensitisation (BOTTOM in pic)
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14
Q

What happens when an allergen is introduced through the oral route?

A
  • When an allergen is ingested through the oral route, Tregs derived from the GI mucosa will inhibit IgE synthesis to keep the immune system in balance
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15
Q

Summarise the Age of Onset of various Allergic Diseases

A
  • Infants
    • Atopic dermatitis
    • Food allergy (milk, egg, nuts)
  • Childhood
    • Asthma (house dustmite, pets)
    • Allergic rhinitis
  • Adults
    • Drug allergy
    • Bee allergy
    • Oral allergy syndrome
    • Occupational allergy
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16
Q

Summarise some theories behind the increasing prevalence of allergic disorders

A
  • Hygiene Hypothesis
    • Lack of childhood exposure to infectious agents increases susceptibility to allergic diseases by suppressing natural development of the immune system
  • Lack of vitamin D in infancy (leading to food allergy)
  • Dietary factors (reduced omega and linoleic fatty acids)
  • High concentration of dietary advanced glycation end-products and pro-glycating sugars which the immune system mistakenly recognises as causing tissue damage (e.g. fast food and soda)
17
Q

What are the Clinical Features of an IgE Mediated Response

A
  • Occurs minutes-3 hours after exposure
  • Symptoms
    • Angioedema (swelling of lips, tongue, eyelids)
    • Urticaria
    • Flushing
    • Itching
    • Cough
    • SOB
    • Nasal congestion
    • Wheeze
    • Red watery eyes
    • Nausea
    • Diarrhoea and vomiting
    • Hypotension (dizziness, faints)
    • Sense of impending doom
  • Usually at least 2 organ systems are involved
  • The symptoms are REPRODUCIBLE (occurs after every exposure)
  • Allergic symptoms can be triggered by co-factors (e.g. exercise, alcohol)
  • The clinical history is used to select what allergens should be tested by skin-prick testing and/or blood tests
18
Q

Summarise the Ix of allergic disease

A
  • Elective Investigations
    • Skin prick and intradermal tests
    • Laboratory measurement of allergen-specific IgE
    • Component-resolved diagnostics
    • Basophil activation test
    • Challenge test (supervised exposure to the antigen)
  • During Acute Episode
    • Evidence of mast cell degranulation
      • Serial mast cell tryptase
      • Blood and/or urine histamine
19
Q

Which tests are the Specific IgE Sensitisation Tests?

What does concentration and affinity to target allergen imply?

Is a positive skin prick test enough to diagnose an allergy?

A
  • Skin prick and blood tests are used to detect the presence/absence of IgE antibody against external proteins
  • IMPORTANT: a positive IgE test only demonstrates sensitisation NOT clinical allergy
  • Risk profile of serum IgE for prediction of allergic symptoms
    • Concentration - higher levels = more symptoms
    • Affinity to target - higher affinity = increased risk
    • Capacity of IgE antibody to induce mast cell degranulation
  • Detection of IgE is necessary but not sufficient to make a diagnosis of allergic disease
    • Diagnosis requires history, examination, blood tests, skin prick tests etc. to be combined
20
Q

Summarise the skin prick test

A
  • Expose the patient to a standardised solution of allergen extract through a skin prick on the forearm
  • Uses a standard skin test solutions with a positive control (histamine) and negative control (diluent)
  • Measure local wheal and flare response to controls and allergens
  • A positive test is indicated by a wheal > 3 mm greater than the negative control
  • Antihistamines should be discontinued for at least 48 hours before the test
  • Skin prick testing is more sensitive and specific than blood tests to diagnose allergy
21
Q

What are the advantages and disadvantages of skin prick tests?

A
22
Q

Summarise the Serum Specific IgE Blood Test

A
  • Allergen is bound to a sponge and the specific IgE (if present) will bind to the allergens
  • This is washed over with anti-IgE antibody which is tagged with a fluorescent label
  • Blood tests are reliable but expensive
  • May help in the diagnosis of an allergic disorder in someone with an appropriate clinical history
  • Higher values are more likely to be associated with allergic disorders
  • Lot of false positives but it has good negative predictive value
  • Concentration of IgE can be used to predict whether a child will outgrow allergy
  • Can be used to monitor anti-IgE therapy
23
Q

What are the indications of Serum Specific IgE Blood Test

A
  • Indications
    • Patients who cant stop antihistamines
    • Patients with dermatographism
      • Development of localised hive-like reaction when the skin is scratched
    • Patients with extensive eczema
    • History of anaphylaxis
    • Borderline/equivocal skin prick test results
24
Q

What is Component Resolves Diagnostics (CRD)

A
  • A blood test to detect IgE to single protein components - abundance and stability of protein contributes to risk of allergic disease
  • Useful for peanut and hazelnut allergy (may reduce need for food challenges)
  • IgE sensitisation to:
    • Heat labile and proteolytic susceptible birch pollen homologue in peanuts and hazelnuts = MINOR symptoms
    • Heat and proteolytic stable seed storage peanut and hazelnut allergen = SEVERE reactions
25
Q

What are the indications for Allergen Component Testing?

A
  • Indications for Allergen Component Testing
    • Detect primary sensitisation
    • Confirm cross-reactivity
    • Define risk of serious reaction for stable allergens
    • Improve diagnostic sensitivity on addition of components which are poorly represented in whole food extracts
    • Improve diagnostic sensitivity for unstable molecules in whole food extracts
26
Q

Name a Biomarker for Anaphylaxis. Summarise.

A
  • Mast Cell Tryptase
  • Tryptase is a pre-formed protein found in mast cell granules
  • Systemic degranulation of mast cells during anaphylaxis results in increased serum tryptase
  • Peak concentration = 1-2 hours
  • Baseline = 6-12 hours
  • Failure of return to baseline after anaphylaxis may be indicative of systemic mastocytosis
  • Useful if the diagnosis of anaphylaxis is uncertain (e.g. hypotension and rash during anaesthesia)
  • Reduced sensitivity for food-induced anaphylaxis
27
Q

Which test is the gold standard for food and drug allergy diagnosis? Summarise

A
  • Challenge Tests
  • Increasing volumes of the offending food/drug are ingested
  • Double-blind placebo or open challenge
  • Take place under close medical supervision
  • Difficult to interpret mild symptoms
  • Risk of SEVERE reaction
28
Q

What is the Basophil Activation Test

A
  • Measurement of basophil response to allergen IgE cross-linking
  • Activated basophils increase the expression of CD63, CD203 and CD300 protein on their cell surface
  • Increasingly used in the diagnosis of food and drug allergy
29
Q

Summarise Anaphylaxis

A
  • DEFINITION: a severe potentially systemic hypersensitivity reaction. Rapid onset, life-threatening airway, breathing and circulatory problems which is usually but not always associated with skin and mucosal changes
  • Incidence: 1.5-8/100,000
  • Skin is the most frequent organ involved (84%)
  • Cardiovascular compromise (collapse, syncope, drop in BP)
  • Respiratory compromise (SOB, wheeze, stridor)
    • NOTE: respiratory symptoms are more common in children
  • Acute onset of symptoms
  • Anaphylaxis is more common in children
30
Q

What are the mechanisms of Anaphylaxis?

A
31
Q

Name some types of anaphylaxis and examples of each type’s inducers

A
32
Q

Name some Reactions that can mimic anaphylaxis

A
33
Q

What is the Mx of anaphylaxis

A
  • IM ADRENALINE is the most important treatment for anaphylaxis
    • Alpha 1 - causes peripheral vasoconstriction, reverses low BP and mucosal oedema
    • Beta 1 - increases heart rate, contractility and BP
    • Beta 2 - relaxes bronchial smooth muscle and reduces the release of inflammatory mediators
  • Supportive Treatments
    • Adjust body position
    • 100% Oxygen
    • Fluid replacement
    • Inhaled bronchodilators
    • Hydrocortisone 100 mg IV (prevent late phase response)
    • Chlorpheniramine 10 mg IV
  • Further Management
  • Referral to allergy/immunology clinic
  • Investigate cause
  • Written information on:
    • Recognition of symptoms
    • Avoidance of triggers
    • Indications for self-treatment with an EpiPen
  • Prescription of emergency kit to manage anaphylaxis
  • Copy of management plan and training for patient, carers, school staff and GP
  • Venom immunotherapy and drug desensitisation as appropriate
  • Refer patients with food-induced anaphylaxis to a dietician
  • Advice patients to get a Medic Alert bracelet
  • Review patient’s understanding
  • Utilise patient support groups (e.g. Anaphylaxis Campaign)
34
Q

What is a food allergy?

What is a food intolerance?

A
  • DEFINITION of Food ALLERGY: adverse health effect arising from specific immune response that occurs reproducibly on exposure to a given food
  • DEFINITION of Food INTOLERANCE: non-immune reactions which include metabolic, pharmacological and unknown mechanisms
35
Q

What are the adverse reactions seen in food allergy or intolerance?

A
36
Q

What must be asked in the Hx if patient says they have food allergy or intolerance

A
37
Q

What are the Ix in food allergy

A
  • Clinical history is important
  • A positive skin-prick test or specific IgE blood test is useful to confirm the diagnosis
  • Testing for individual allergen protein component can distinguish between IgE-sensitisation and IgE-mediated allergy
38
Q

What is the Mx of food allergy?

A
  • Avoidance
  • Anaphylaxis guidance for emergencies
39
Q

Name some IgE Mediated Food Allergy Syndromes

A

4 - Y5 a Path lectures 2021/22 (37 decks)

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