Hypersensitivity Flashcards
What is hypersensitivity?
Hypersensitivity = exaggerated, inappropriate adaptive immune response to harmless environmental antigens.Sometimes inflammatory reactions and tissue damage result.Can be provoked by range of antigens.Not manifest on first contact with Ag.Usually appears on subsequent contact.(Response to what would normally be harmless. Non-pathogenic.Features will not manifest on first contact with antigen- features happen on subsequent contact.)
What are the four classifications of hypersensitivity?
Type I, II, III and IV.Types I, II, III - Antibody mediated.Type IV - mediated by T cells and macrophages.May have more than one occurring at same time.Order here- occurs fastest to slowest (eg. I is fastest, then II, III, IV etc.).
What substances can cause hypersensitivity?
Inhaled materials: plant pollens, dander of domesticated animals, mold spores, feces of very small animals eg. house dust mites.Injected materials: insect venoms, drugs, therapeutic proteins.Ingested materials: food, orally administered drugs.Contacted materials: Plant leaves, industrial products made from plants, synthetic chemicals in industrial products, metals.
What is type I (immediate) hypersensitivity?
IgE response (sensitization) to innocuous environmental antigens- pollen, house dust mite feces, animal proteins.IgE is located mainly in tissues, binds to FceRI (Fc receptor that binds IgE) on mast cells, basophils and activated eosinophils.Second encounter with allergen triggers release of inflammatory mediators.produces acute inflammatory reaction within minutes- effects seen straight away.Symptoms of varying severity, from running nose (rhinitis) to breathing difficulties and even death by asphyxiation.
What is the structure of monomeric IgE?
Usual immunoglobulin structure.Heavy chain has 4 constant regions.Heavily glycosylated- n-linked glycosaccarides.Fc receptor binds to CH3 domain.
What are mast cells?
Resident in mucosal and epithelial tissues lining body surfaces.Present in all vascularized tissues except CNS and retina.Maintain tissue integrity. Alert immune system to local trauma and infection.Facilitate repair of damage caused by infection or wounds.50-200 granules fill the cytoplasm.Vesicles contain histamine and other inflammatory mediators.
What happens to mast cells during degranulation?
Empty out the contents of the granules- can do this quite rapidly.Package of preformed mediators that can be released immediately.
How does antigen binding to IgE on mast cells cause an inflammatory response?
IgE has long half life of residency (2 weeks) when bound to receptor.High affinity interaction- (Kd ~ 10^10M-1) – means binding is very long lived.Mast cells primed with IgE.IgE would have binding sites for specific anitgen (when encountered once), for if it encounters it again.Immobilise Fc receptors in clusters.Signalling pathways triggered- receptor cross-linking -> Lyn and syk kinases-> Degranulation and release of histamine, prostaglandins,leukotrienes and other mediators of allergic response.Long binding is why response is so immediate.
What does histimine do?
Constricts airways, increase mucus secretion- leads to sneezing coughing and wheezing.
What are eosinophils?
Release toxic mediators in IgE response.Mostly resident in connective tissue underlying mucosal epithelia.Have a characteristic staining pattern in histological sections.In inflammatory response, cytokines and chemokines at site induce eosinophils to express FcεRI.Also have granules- can also degranulate.Stain with eosinFc expresssion- can now respond to IgE.Activated eosinophils secrete toxic proteins contained in their granules and also produce cytokines and inflammatory mediators.Usually very effective at killing parasites, but turn on our own tissues in hypersensitivity.
What are basophils?
Granules contain similar, but not identical, set of mediators to those of mast cells.Recruited to tissue under appropriate stimulation.Similar effector function to eosinophils.
What affects type I hypersensitivity symptoms?What are some reactions and what causes them?
Type I hypersensitivity symptoms vary with site of entry of allergen.Systemic anaphylaxis (most severe form of type I hypersensitivity): caused by drugs, serum, venoms, peanuts. Causes oedema, increased vascular permeability, tracheal occlusion, circulatory collapse, death.Wheal and flare (swelling and redness): caused by insect bites, allergy testing. Causes local increase in blood flow and vascular permeability.Allergic rhinitis (hayfever): caused by pollens, dust mite feces. Causes oedema, nasal mucus, irritation of nasal mucosa.Bronchial asthma: caused by pollens, dust mite feces. Causes bronchial constriction, increased mucus production, airway inflammation.Food allergy: caused by shellfish, milk, eggs, fish, wheat etc. Causes vomiting, diarrhoea, itching, hives, anaphylaxis.
What are the shared properties of inhaled allergens?
Usually proteins, as they only induce T-cell responses (molecular type).Often proteases (function).Favour activation of IL-4-producing CD4 Tcells (low dose).Allergen can diffuse out of particle into mucus (low molecular weight).Allergen is readily eluted from particle (high solubility).Allergen can survive in desiccated particles (high stability).Contains peptides that bind host MHC class II- required for T cell priming.
How can pollen sensitisation occur?
Antigens that leach from inhaled pollen are taken up by APC in airway mucosa. (Pollen can leach across epithelium and be picked up by antigen presenting cells.)These activate naive T cells to become TH2 effector cells, which secrete IL-4.IL-4 binds to the B cell’s IL-4 receptor.B cell is induced to switch Ig isotype and secretes IgE.IgE binds to FcεRI on mast cells. Mast cells now primed with antigen specific IgE.
What are the two stages of an allergic reaction?
Allergic reactions have an immediate reaction followed by a late-phase reaction.Bi-phasic response.Immediate- localised swelling at point of injection, redness (wheal and flare- 15 mins).Late- 6 hrs- generalised swelling.
