Atopy, allergy and delayed type hypersensitivity Flashcards
Define the early phase allergic reaction
- exposure to allergens leads to rapid development of symptoms in allergic individual
- develops withins seconds/minutes as allergens bind to preformed IgE on surface of mast cells and basophils
Explain how the early phase allergic reaction happens
IgE bind to specific allergen
Cross linking of IgE by allergen leads to clustering of Fc3R1 receptors. The intracellular portion of recptor is phosphorylated –> intracellular cascade –> cellular activation –> mast cell degranulation releasing histamine, tryptase and other preformed mediators
What are leukotrienes
Delayed mediators pharmacologically similar to histamine
Its effects
- skin: wheal and flare
- nose: discharge, sneezing
- eyes: conjunctivitis
- lung: wheeze
State the effects of mast cell activation and degranulation on
- GIT
- Airway
- Blood vessels
- expulsion of GIT contents by diarrhoea, vomit
- congestion and blockage of airways; swelling and mucus production in nasal passages
- increased fluid in tissues causing increased flow of lymph to nodes, increased cells and protein in tissues and increased effector responses in tissues
What is the source of allergen antigens?
Almost always innocuous environmental proteins
- pollens, housedust mite faeces, stinging insect venom
Describe the general characteristics of allergens
What are the physical properties that favour transition across mucus membranes?
Why is this important?
Why is homology relevant?
- All proteins- only proteins can produce a T cell (and therefore B cell) response
(most are biologically active, enzymes. Could be coincidental) - soluble, LMW
- need to cross mucus membranes to activate immunity
- Low homology wont bind MHC, high homology wouldve been deleted during negative selection. Therefore allergens must have intermediate homology
What is anaphylaxis?
What happens?
What are the commonest triggers in the UK?
Generalised allergic reaction
Systemic release of histamine causes generalised vasodilation and fluid loss from circulation to tissues
- Cutaneous: hives, angiodema
- Gut histamine release: laryngeal oedema, bronchoconstriction
- Circulation: vasodilation, hypotension
- Food, drugs, insect venom
What are the cardinal features of anaphylaxis
- Typical symptoms: hives, angioedema, laryngeal oedema, bronchoconstriction, hypotension
- multisystem and dramatic
- rapidly follows exposure to allergen
- improves quickly
Describe oral allergy syndrome
- most common allergy
- IgE directed pollen proteins cross react with homologous proteins in plant derived foods
- Oral itching upon exposure to raw fruit, nuts and vegetables
- In the UK: pollen (mainly birch) and food (mainly rosaceae fruits)
Rhinitis and lower airway obstruction are types of airway disease. Describe them.
Exposure to allergens can be seasonal or episodic. Give examples
What happens if the symptoms are chronic?
Rhinitis: sneezing, rhinorhoea, blockage due to type 1 allergy
Lower airway obstruction: wheezing due to type 1 allergy
Seasonal: pollen, moulds
Episodic: occupational, animal dander
If symptoms are chronic, the inflammation becomes established ad cannot be explained in terms of mast cell degranulation
What is meant by the immunological tightrope?
The immune system must strike a balance between
Activation: required for defence against infection and cancer
Tolerance: required to prevent autoimmunity and inflammatory diseases
What are the origins of allergic disease?
allergic/atopic march = progression of disease from infancy
- most children will outgrow eczema and food allergies
(rhinitis and asthma may not be outgrown)
de nova presentation in adults
Describe symptom progression of asthma, sensitisation, histopathology and comment on the application of early phase reaction as an explanation of asthma
- ongoing symptoms
- most patients are sensitised to a variety of airborne allergens
- biopsy shows inflammatory infiltrate and airway changes (REMODELLING) such as thickened basement membrane and smooth muscle hyperplasia
- early phase reaction doesnt provide good explanation
Describe the late phase allergic reaction
- develops after some hours
- biopsy shows infiltration with inflammatory cells: CD4 T cells, eosinophils, mast cells
T helper cells and Treg are CD4+ cells.
Which cytokines are produced from TH1, TH2, TH17 and Treg
Th1 –> IFN-y
Th2–> IL4,5,9,13
Th17 –> IL17
Treg –> IL10, contact dependent mechanisms
Which cytokines are important in allergic disease?
- Allergic inflammation is rich in T cells expressing Th2 cytokines
IL4 is required for B cell class switch to IgE
IL13: bronchial hyperesponsiveness
IL4 and IL13 promotes mucus hypersecretion
IL5 required for eosinophil survival and recruitement
IL9 recruits mast cells
Differentiate between the role of acute and chronic responses in asthma
Acute responses: inflammatory mediators cause an increase in mucus secretion and smooth muscle contraction –> airway obstruction, recruitement of cells from circulation
Chronic responses: caused by cytokines and eosinophils products. Activated Th2 cells and other inflammatory cells accumulate and products of Th2 lead to chronic disease
(IL4,5,9,13)
Describe how genetics is a potential factor in the aetiology of allergy
- childhood allergy strongly predicted if parents have allergies
- numerous genetic Rx factors identified
BUT…. doesnt explain epidemic
Describe how hygiene hypothesis (Strachan 1989) is a potential factor in the aetiology of allergy
- In westernised countries there are SMALL family sizes, AFFLUENT/URBAN homes, STABLE instestinal microflora, HIGH ANTIBIOTIC use, low/absent HELMINTH burden, good sanitation, low OROFAECAL burden
- This promotes allergic disorders
- Low hygiene levels and high pathogen load, helminth infection skews immunity from Th2 to Th1 and induces Treg.
Describe the process involved in a SKIN TEST and what it is used for
- Indication
Used to detect allergen-specific IgE in vivo. Indicated if patient history suggestive of IgE-mediated allergy
- Allergen extract applied as drops
- Top layer of epidermis punctured with lancet
- WHEAL AND FLARE response after 15 minutes = positive result
* needs interpretation in clinical context
Describe the process involved in a RAST and what it is used for
Type of ELISA used to detect allergen-specifc IgE in vivo
- Patient serum incubated in well coated with purified allergen
- IgE in sera of sensitised patient binds allergen
- Immobilised IgE antibodies detected with polyclonal anti-IgE detection antibody
Pure symptoms relievers are used in treatment of allergy
NASAL DECONGESTANTS
- example
- MOA
- Route of administeration
- Period of use
- Oxymetazoine
- Vasoconstriction via a1 adrenoreceptors
- Topical and systemic
- Short term use
Pure symptoms relievers are used in treatment of allergy
SALBUTAMOL
- class of drug
- MOA
- B2 agonist
- Smooth muscle relaxation via B2 adrenoreceptors on lung
Pure symptoms relievers are used in treatment of allergy
EPINEPHRINE
- MOA
- Oppose vasodilation and bronchoconstriction via systemic adrenergic effects
