** Immuno 3: Allergy Flashcards
(39 cards)
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
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
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
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
5
Q
What are the 2 types of immune response to an allergen?
A
- Th2
- mast cell
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
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
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
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
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
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
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
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)
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
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
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
- Evidence of mast cell degranulation
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
What are the indications for **Allergen Component Testing?**
* **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
Name a **Biomarker for Anaphylaxis.** Summarise.
* **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
Which test is the gold standard for food and drug allergy diagnosis? Summarise
* **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
What is the **Basophil Activation Test**
* 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
Summarise **Anaphylaxis**
* 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
What are the mechanisms of Anaphylaxis?
31
Name some types of anaphylaxis and examples of each type's inducers
32
Name some **Reactions that can mimic anaphylaxis**
33
What is the Mx of anaphylaxis
* **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
What is a food allergy?
What is a food intolerance?
* 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
What are the adverse reactions seen in food allergy or intolerance?
36
What must be asked in the Hx if patient says they have food allergy or intolerance
37
What are the Ix in food allergy
* 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
What is the Mx of food allergy?
* Avoidance
* Anaphylaxis guidance for emergencies
39
Name some **IgE Mediated Food Allergy Syndromes**
