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45 Cards in this Set
- Front
- Back
What is hypersensitivity? |
First contact with antigen - immunologically primed
Further contactwith the antigen leads to a secondary reaction. If excessive, tissue damage. |
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What is different in hypersensitivity response? |
•largequantities of the antigen or the immune system response is increased. |
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Types
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–Type IV dependent on T cell recognition. Delayedtype hypersensitivity –TypesI, II, III and V depend on antigen-antibody reactions. Immediatetype reactions. |
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Type I What is produced? Which cells are induced? Type of reaction |
Production of IgEagainst innocuous antigens – induces mast cell activation, anaphylactic,immediate reaction |
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What triggers mast cell degranulation? |
•IgE strongly bound to the plasma membrane bya high affinity receptor.
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Source of IgE
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· IgE produced by plasma cells in lymph nodes andby plasma cells at site of allergic reaction (mucosal tissue/skin) · IgE predominantly located in tissues, tightlybound to surface of mast cells. |
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Cause ofanaphylaxis |
· On subsequent exposure of Ag, contraction ofsmooth muscle and dilation of capillaries. Injection of penicillin or beestings.
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What is Anaphylaxis? How is it shown? |
degranulationof mast cells by binding of Ag to IgG strongly bound to plasma membrane by highaffinity receptor - releases histamine (acting on H1 receptors onlocal blood vessels) and other mediators causing a rapid increase in vascularpermeability. Show by injecting histamine to guinea pig. |
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What is Anaphylacticshock? How is it controlled? |
widespreadincrease in vascular permeability from massive release of histamine – largeloss of BP so shock with airways constriction. Controlled with adrenalineinjection – reverses action of histamine. |
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involvement of penicillin |
–highly reactive beta-lactam reacts with amino group on host proteins to formcovalent conjugates (haptens) with self-proteins provoking a TH2 response insome individuals – induces IgE synthesis. TH2 activate penicillin-binding Bcells to produce IgE against penicillin hapten.
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Types of mast cells and location, expression |
•mucosal - gut and lung mucos. •tryptase chymase connective tissue - most other tissues including theperitoneal cavity and other connective tissues. These cells express Tryptase |
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Ratio of LTC4 : PGD 2 release |
Mucosal25 : 1 (more LT) Connective1:40 (more PG) |
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Mast cell receptor |
· Both possess high affinity IgE receptor: alpha subunit binds to the Fc regionof IgE with v. high affinity. Beta and gammasubunits are involved in signal transduction. Found in cholesterol-rich lipidrafts. |
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What binds to mast cell receptors? |
· Multivalent haptens bind to multiple IgEs boundto receptor – crosslinks IgE receptors which triggers secretion of inflammatorymediators.
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Effect of receptor crosslinking?
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· More receptors crosslinked together increasessensitivity of cells to Ag. |
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How do LTC4 and PGD2 work? |
•G protein coupled receptors. |
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What is Atopy? |
hyperallergic predispositionto become IgE-sensitised to environmental allergens |
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Allergic rhinitis? Prevalence, mechanism |
· 10% of population, airborne allergensinteracting with sensitised MCs in conjunctivae and/or nasal mucosa. · Activation of mucosal MCs beneath nasalepithelial by allergens – diffuse across the mucous membranes of nasal passages · MC mediators cause local vasodilation andincreased capillary permeability |
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cause of Food allergies
Mechanism |
· Allergen induced IgE crosslinking in upper/lowerGI tract – causes localised smooth muscle contraction and vasodilation. · MC activation – may increase guy permeability toallergens. |
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When can Sensitisation to dietary allergens occur? |
· inearly infancy through breastfeeding, with antigen passing into mother’s milk. |
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Atopic Dermatitis |
· Allergic eczema – high serum IgE levels, Th2cells and eosinophils in infiltrate |
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Atopic allergy – treatment - first |
· Avoidance – advised after sensitisation. Avoidcontact with potential allergens can be impractical; |
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Desensitisation treatment How it works |
· Desensitisation to Ag after identification ofallergen. Repeated subcutaneous injection of increasing doses of Ag – reduceseverity of type I reactions in SOME patients. Appears to generate IgG reactionto Ag. IgG may compete to bind to allergen, blocking IgE binding. |
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Currentresearch |
· produce modified recombinant known allergens. |
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Immunotherapyfor food allergies - best result so far |
· Oral – best results so far, sublingual orepicutaneousSublingual allergen immunotherapy (SLIT) – lessrisk of severe systemic reactions than subcutaneous admin but not as effectiveas injections
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Aims in Immunotherapy for food allergies |
Aim was to boost synthesis of IgG “blocking” Abs –divert allergen from contact with tissue-bound IgE. Also, downregulation of IgEsynthesis. Alternatively, may induce regulatory T cells and switch from Th2 toTh2 cytokine production. |
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What is Desensitisation |
· restore tolerance by reducing tendency to induceIgE production |
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Alternative therapy |
vaccinationwith peptides derived from common allergens; induces Treg cells andproduction of IL-10. IgE-mediated response is not induced by peptide – tooshort to cross-link IgE |
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What is type II? |
antibodydependent cytotoxic •Bindingof an antibody to antigen on a cell surface may result in the destruction ofthe cell by phagocytosis –Leadsto opsonisation of cell – leads to phagocytosis oractivation of complement (MAC) |
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Cause of MAC
With example |
•May be due to adherence of the phagocyticcell to the Fc region of the antibody or via bound C3 –autoimmune thrombocytopaenic purpura |
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Type II - alternative killing method |
•Targetcells coated with low concentrations of IgG may also be killed by antibody dependentcell-mediated cytotoxicity (ADCC) |
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Example of type II hypersensitivity in rbcs |
Autoimmunehaemolytic anaemia
rbcs - only require one active complement siteto destroy the cells |
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What is type III? |
(Immunecomplex mediated
•Occurs whenpatient is exposed to large quantities of antigen over a prolonged period –antigen and antibody may react to forminsoluble complexes at fixed sites within the body |
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When does it occur
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–may occur with persistent infections,autoimmune diseases or repeated exposure to an environmental antigen.
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Effect of deposition ofantigen-antibody complexes |
Complement - release of C3a and C5a - activates mast cells and increasesvascular permeability –releaseof chemotactic factors which leads to an influx of polymorphonuclear leukocytes - full complement - MAC complex |
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What is Arthusreaction? |
•Complexesdeposited in blood vessels may lead to platelet aggregation –releasevasoactive amines (increased vascular permeability) –mayform microthrombi, blocking capillaries which produces alocalised ischaemia. |
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What is Arthusreaction the basis of ? |
•rheumatoid arthritis
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What is type IV? |
delayedtype - •Notdependent on antibody reactions •Dependenton lymphoid cells –particularlyT-lymphocytes |
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What causes the response? |
Tissue damage bymacrophage activation by Th1; eosinophils – Th2; CTLs
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Type V |
stimulatory •formation of autoantibodies to cellsurface receptors on lymphocytes –Some of these antibodies may inappropriatelyactivate the cells |
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Example of disease
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–Gravesdisease
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Innatehypersensitivity reactions |
•Some infections induce toxic shocksyndrome –characterised by hypotension, hypoxia, oliguria andmicrovascular abnormalities |
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Innatehypersensitivity reactions- Gram-negative |
•Gram-negativebacteria can provoke septicaemia bythe action of lipopolysaccharide (LPS) |
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Explain the mechanism |
· Endotoxin acts on macrophages and endothelialcells – excessive release of TNF, IL1 and IL6.
LPS can activate alternativecomplement pathway – activates platelets – disseminated intravascularcoagulation. |
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Innatehypersensitivity reactions- Gram-positive |
S.aureus binds macrophages – induces TNFa synthesis; –peptidoglycanin the cell wall can aggregate platelets –Inaddition the staphylococcal enterotoxin is a superantigen |