Core Immunology - Allergic Diseases (11) Flashcards
Allergy
Undesirable, damaging and sometimes fatal reaction produced by immune system, directed against innocuous antigens in a pre-sensitised (immune host)
Immunopathological classification
Coombs and Gel 1963 - IV types, extended classification - type V
Type 2 allergy
Cytotoxic
Type 2 immunopathogenesis
IgG/IgM Ab response against self/foreign antigen at cell surface - complement activation/phagocytosis/ADCC
Type 2 clinical features
Onset minutes to hours, cell lysis and necrosis
Type 2 common antigens
Penicillin
Type 2 associated diseases
Erythroblastosis fetalis, Goodpasture’s nephritis
Type 3 allergy
Immune complex
Type 3 immunopathology
IgG/IgM Ab against soluble antigen (immune complex deposition)
Type 3 clinical features
Onset 3-8 hours, vasculitis
Type 3 cause
Serum sickness
Type 3 associated diseases
SLE
Inhaled >
Farmer’s lung, alveolar/capillary interface
Type IV allergy
Delayed
Type IV clinical features
Delayed onset 48-72 hours, erythema induration
Type IV common antigen
Metals - nickel (tuberculin reaction)
Type IV associated diseases
Contact dermatitis
Immune response to parasitic disease
Increased IgE, specific to pathogen (cross-reactive), tissue inflammation (eosinophilia, mastocytosis, basophil infiltration), presence of CD4+ T cells secreting (IL4, IL5, IL13)
Hygiene hypothesis
Microbes stimulation is protective, increase asthma after anti-parasitic treatment, prevention of autoimmunity, pro-biotics in pregnancy (Th1 Th2 deviation)
Genetic influence on allergic immune response - polygenic disease, cytokine gene cluster (IL3,5,9,13), IL12R, IL4R, FC3RI, IFNy, TNF, Not sufficient for disease, only suscepibility
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4 groups of susceptibility genes for allergic disease
- Sensing the environment
- Barrier function
- Regulation of (atopic) inflammation
- Tissue response genes
Allergens
Antigens that initiate an IgE-mediated response, first encounter results in innate and IgM response
Conventional immune response
Allergen requires processing, presentation to T cells, cytokine release > delineation of T-helper subsets into different types
IgE production
Th2 cell stimulates B cell with IL-4, stimulates B cell proliferation > IgE release
Type 1 allergy
Fc receptor for IgE on mast cell > degranulation > vasoactive amines > smooth muscle, blood vessel mucous gland, platelets, sensory nerve endings > eosinophil
Primary mediators released from degranulation (initial response)
Histamine, proteases, chemotactic factors
Secondary mediators (late-phase response)
Membrane phospholipid > Arachidonic acid > leukotrienes and prostaglandin
Role of Th2
Multiple cytokine release - innate inflammatory response (IL-4 and IL-13), drive for Ig production
Th1 cells produce
IFN and TNF
Role of Th1
Activation and apoptosis of keratinocytes, bronchial epithelial cells and pulmonary smooth muscle (activation of mast cells and basophils > histamine)
Atopic triad
Asthma, rhinitis, eczema
Allergic rhinitis
Nasal congestion (oedema, mucus, nasal polyps)
Asthma
Airway inflammation (oedema, mucus)
Rhinitis allergic
Perennial/seasonal (allergic/non-allergic)
Rhinitis symptoms
Blocked nose, runny nose (eye symptoms)
Antigens for Rhinitis
House dust mite, animal danders
Rhinitis treatment
Antihistamines and nasal steroids
Early phase response/acute allergic symptoms
Mucus hypersecretion, increase of vascular permeability (oedema), vasodilation, C-sensory nerve stimulation)
Late phase response/chronic allergic inflammation
Sneezing, nasal itching, rhinorrhea, nasal obstruction, occular symptoms, nasal hyperresponsiveness
What is asthma?
Disease of inflammation and hyper-reactivity of small airways
Asthma in childhood
Aero-allergic stimuli (house dust mite)
Asthma immediate symptoms are mediated by what
IgE
Asthma damage to airways due to
Late phase response (infiltration of eosniphil, lymphocyte, Th, basophil), hyper-reactive to non-allergic stimulis (fumes)
Pathogenesis of asthma
Allergen > APC > Th2 > IL-5/IL-4/13 > eosinophil/mast cell basophil > histamine, leukotrienes, prostaglandins, cytokines > allergic asthma
Contact dermatitis
Allergic/non-allergic
Atopic dermatitis clinically
Intense itching, blistering/weeping, cracking of skin
Major trigger in atopic dermatitis
House dust mite
Treatment for atopic dermatitis
Topical steroids and moisturisers
How do you get pruritus?
Th2 - IL-31 > pruritus/scratch
Anaphylaxis
Acute, life-threatening, IgE mediated systemic hypersensitivity reaction
Diagnosis of allergy
- Specific IgE (>0.35)
- Skin prick test (>3mm)
- Intra-dermal test
- Oral challenge test (gold standard)
- Basophil activation test
- Component resolved diagnostics
Basophil activation test
When IgE, upregulate expression of markers (CD63, CD203c, CD300a) > activated
Advantages of specific IgE
Safe
Disadvantages of specific IgE
False negatives and positives
Advantages of skin prick test
Quick, patient satisfaction
Disadvantages of skin prick
False negatives and positives, antihistamines, slight risk
Treatment
Antihistamines, steroids, adrenaline, immunotherapy (subcutaneous/sublingual)
Indications for treatment
Life threatening reactions to wasp, bee sting, severe hay fever, animal dander allergy
Not helpful for treatment
Multiple allergies, food allergy, allergic rashes (eczema, urticaria)
Major food allergens
Cow’s milk, egg, legumes (peanut, soybean, tree nuts), fish, crustaceans/molluscs, cereal grains
Adverse food reactions - GI clinical
Vomiting, diarrhoea, oral symptoms
Adverse food reactions - resp clinical
Rhinitis and bronchospasm (anaphylaxis)
Adverse food reactions - cutaneous
Urticaria, angioedema, role of food in atopic dermatitis unclear
