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154 Cards in this Set
- Front
- Back
Where are the effects focused when re-exposure to allergen triggers an allergic reaction? |
Site which mast cell degranulation occures |
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What is characteristic of the preformed mediators in the immediate response? |
Effects are: short-lived confined to vicinity of activated cell |
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What is characteristic about the late phase response? |
Sustained effect Still confined to site of initial allergen-triggered activation Particular anatomy of site may determine readily if the inflammation can be resolved |
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What does the clinical syndrome produced by an allergic reaction depend on? |
Amount of allergen-specific IgE present Route by which allergen is introduced Dose of allergen |
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What determines the type of IgE-mediated allergic reaction? |
Dose & route of allergen administration |
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What are the 2 main anatomical distributions of mast cells? |
Connective tissue mast cell (vascularized CT) Mucosal mast cells (submucosal layers of gut) |
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All mast cells at anatomical spaces are loaded with IgE directed against specific allergens. The overall response to an allergen then depends on which _____ _____ are activated |
Mast cells |
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Which MC do allergens in the bloodstream activate |
CTMC resulting in systemic release of histamine & other mediators. |
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Which MC does subcutaneous administration of allergen (skin) activate? |
Local CTMC, leading to local inflammation. Manifest as wheal-and-flare |
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In atopic individuals airborne allergens penetrating the skin may lead to atopic eczema. |
True |
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What does an inhaled allergen induce? |
Penetrates mucosal epithelial Activates MMC mainly Increased mucus secretion Irritation in nasal mucosa Allergic rhinitis/additional bronchoconstriction |
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What does an ingested allergen do? |
Penetrates gut epithelium Vomit due to smooth muscle contraction Diarrhoea due to outflow of fluid across epi |
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What else can happen to food allergens? |
Disseminated in the bloodstream Widespread urticaria when allergen reaches skin, or eczema |
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Allergen introduced directly into the bloodstream can cause ____________ |
Anaphylaxis |
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What is a mild & extreme symptom of release into bloodstream? |
Urticaria (hives) Anaphylactic shock- potentially fatal |
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When is acute urticaria caused? |
Ingested allergens released into the bloodstream & reaches skin Histamine causes large itchy, red swelling all over the body |
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What does anaphyliactic shock lead to? |
Widespread increase in vascular permeability – resulting from massive histamine release Catastrophic loss of BP-> shock Airway constriction-> difficulty breathing Epiglottis swelling-> suffocation |
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What are some major causes of anaphylactic shock? |
Wasp & bee stings Allergic responses to foods e.g. peanuts |
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Anaphylactic shock can be rapidly fatal. What can reverse the histamine reaction? |
Immediate epinephrine injection |
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What is another pharmaceutical way that anaphylactic shock can occur? |
Drug is administered to people who have IgE specific antibodies for that drug |
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What is nature's way of inducing an anaphylactic shock? |
Individuals allergic to insect venom from a bite |
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The most frequent reactions to drugs occur with _________ and its relatives. |
Penicillin Administration by injection can cause anaphylaxis & even death |
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What are inhaled allergens associated with? |
Development of rhinitis & asthma |
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Most common route of entry |
Respiratory |
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What is allergic rhinitis? |
Atopic people have mild allergies to inhaled antigens, manifesting as sneezing and a runny nose |
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How does allergic rhinitis result? |
MMC activation beneath the nasal epithelium by allergens (e.g. pollens that release their protein contents) which then diffuse across the mucous membranes of the nasal passages. |
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How does allergic conjunctivitis occur? |
Airborne allergens deposited on the conjunctiva of the eye |
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Allergic rhinitis and conjunctivitis are commonly caused by _______________ allergens that are present only during certain seasons of the year. |
Environmental e.g. hay fever (seasonal allergic rhinoconjunctivitis)- diverse causes- grass & tree pollens. |
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What causes some summer & autumnal symptoms of hay fever? |
Weed pollen such as ragweed |
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What are perennial Ag? |
Cat dander and house dust mites can cause year-round misery. |
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How is allergic asthma triggered? |
Allergen-induced activation of submucosal mast cells in the lower airways |
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The same allergens that cause allergic rhinitis and conjunctivitis commonly cause asthma attacks. |
True |
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Allergic asthma can be life-threatening, but doesn't need immediate treatment |
False |
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What happens within seconds after an allergen is inhaled? |
Bronchial constriction Increased secretion of fluid & mucus Breathing difficult Inhaled air trapped in lungs |
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What is an important feature of asthma? |
Chronic inflammation of the airways |
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What characterises chronic inflammation of the airways? |
Continued presence of increased numbers of TH2 lymphocytes, eosinophils, neutrophils, and other leukocytes |
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What do immune cells cause? |
Airway remodelling |
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What happens in airway remodelling? |
Thickening of the airway walls due to hyperplasia & hypertrophy of the smooth muscle layer & mucous glands Eventual development of fibrosis & permanent airway narrowing. |
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What happens in chronic asthmatics? |
General hyperreactivity of the airways to non-immunological stimuli also develops. |
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What are some of these non-immunological stimuli? |
Cigarette smoke SO2 |
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What else might exacerbate acute response in allergic asthma? |
Viral infections Induces Th2-dominated local response Cytokine secretion by Th2 cells & MC Augment eosinophil activation & degranulation Chronic inflammation |
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Allergy to foods causes systemic reactions as well as symptoms limited to the gut |
True |
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What % of the American & European populations does genuine food allergy affect? |
1-4% |
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Which ubiquitous factors are often misnamed as allergy by the sufferer? |
Food intolerance Dislikes |
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Which food item causes allergy in ~ 1/4 of US/European citizens? |
Peanuts, increasing incidents |
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What are the 2 types of allergic responses seen when an allergen is ingested? |
Activation of MMC associated with GIT CTMC in the dermis & subcutaenous tissues |
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What does activation of MMC associated with GIT cause? |
Diarrhoea & vomitting |
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What can CTMC result in? |
Urticaria Ingestion of food allergen-> development of asthma & anaphylaxis with circulatory collapse |
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How can IgE-mediated allergic disease be treated? |
Inhibit effector pathways that lead to symptoms or by desensitization techniques that aim in restoring tolerance to the Ag |
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What do antihistamines treat? |
Symptoms only |
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What are corticosteroids? |
General inflammatory drugs |
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Current drug treatments are largely ____________, than curative, often need to be taken for life. |
Palliative |
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What is used to treat anaphylactic reactions? |
Epinephrine |
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How is epinephrine useful? |
Stimulates reformation of endothelial tight junctions Promotes relaxation of bronchial smooth muscle constriction Stimulates the heart |
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What are inhaled bronchodilators? |
Acts on β-adrenergic receptors Relax constricted muscle are used to relieve acute asthma attacks |
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How do antihistamines reduce urticaria? |
Blocking H1 receptors |
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How does urticaria result? |
Release of histamine from MC & basophils |
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It is important to treat and prevent chronic inflammatory injury to tissues |
True |
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What are corticosteroids? |
Used to suppress chronic inflammatory changes seen in asthma, rhinitis & eczema Topical or systemic |
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A means of regulating the T-cell response to the allergenic peptide antigen in an ________________ manner is needed. |
Antigen-specific |
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What are the 2 treatments commonly used in clinical practice? |
Desensitisation or specific allergen immunotherapy Blockade of effector pathways |
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What does desensitization aim to restore? |
Tolerance to the allergen by reducing its tendency to induce IgE production |
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What is the key to the desensitization? |
Induction of T-cells secreting IL-10 and/ or TGFβ, which turn the response away from IgE. e.g. beekeepers- naturally protected- IL-10 secreting T cells Injection with increasing doses of allergen that gradually decreases IgE-dominated response |
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Which Ig is produced with increased IL-10? |
IgG4, subtype selectively promoted by IL-10 |
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What does allergen injection immunotherapy downregulate? |
TH1- and TH2-driven hypersensitivity disease, with its induction of Treg-cells. |
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What is desensitization also associated with? |
Reduction in the numbers of late-phase inflammatory cells at the site of allergic reaction |
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What is a complication of the desensitization? |
Risk of inducing IgE-mediated allergic responses e.g. treating severe reactions against peanut allergy |
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What is an alternative approach to desensitization? |
Vaccination with peptides derived from common allergens. Induces Treg cells which produce IL-10 |
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IgE-mediated responses are not induced by peptides. Why? |
Recognizes only intact allergens |
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Patients with different MHC class II molecules respond to different allergen-derived peptides. |
True |
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What is another approach? |
Give cytokines that promote Th1 type responses. |
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Which cytokines can reduce IL-4-stimulated IgE synthesis? |
IFNγ, IFNα, and IL-12 |
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Administration of which cytokine can cause adverse side effects? |
IL-12 |
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What is another target for therapeutic intervention? |
High affinity IgE receptor |
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What will an effective competitor for IgE result in? |
Prevents binding of IgE to surfaces of MC, basophil & eosinophils |
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What is Omalizumab? |
Humanised anti-IgE monoclonal antibody Binds to portion of IgE that ligates the high affinity IgE receptor |
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What does omalizumab bring about? |
Decrease in IgE levels |
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What else is an effect? |
Downregulation of the no. of high affinity IgEr on MC & basophil |
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What was observed of Omalizumab in experimentally inhaled allergen? |
Ab blocks both immediate & late-phase responses |
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What is a potential target when blocking recruitment of eosinophils to sites of allergic inflammation? |
CCR3 |
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What does a blockade of IL-5 cause? |
Production of eosinophils in BM & their exit into circulation is reduced |
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Innocuous antigens can cause Type __ hypersensitivity reactions in susceptible individuals by binding to the surfaces of circulating blood cells |
II |
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What do antibiotics like penicillin & cephalosporin do to some cells? |
Cause antibody-mediated destruction of RBC (haemolytic anaemia) or platelets (thrombocytopenia) |
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What happens in type II hypersensitivity reactions? |
Drug binds to the cell surface & serves as a target for anti-drug Ab that destroy the cell Cell-bound Ab triggers clearance of cell from circulation |
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What is the predominant means by which the cell-bound Ab are cleared from circulation? |
Tissue macrophages in the spleen which bear Fcγ receptors. |
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What causes systemic disease? |
Immune-complex formation following administration of large quantities of poorly catabolised Ag |
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Type III hypersensitivity reactions can arise with soluble antigens |
True |
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What is an immune complex? |
Ag:Ab |
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Pathology of type III hypersensitivity |
Immune complex at the tissues and sites |
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What happens to larger IC? |
Aggregates fix C' Readily cleared from circulation by the mononuclear phagocyte system |
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What happens to smaller IC? |
Forms when Ag is in excess Deposited in BV walls Ligates FcR on leukocytes-> leukocyte activation & tissue injury |
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What is a local type III hypersensitivity reaction called? |
Arthus reaction |
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How is an Arthus reaction triggered? |
In the skin of sensitized individuals who possess IgG Ab against the sensitizing Ag |
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What happens when Ag is injected into skin? |
Circulating IgG Ab diffuses into skin forms IC locally |
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What do these IC do? |
Bind FcR (FcγRIII) on MC & other leukocytes Local inflammatory response Increased vascular permeability Fluid enters inflammatory site from local BV |
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What other component of the IS do IC activate? |
C', generating C5a which attracts cells to inflammatory site |
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What components are required for the experimental induction of an Arthus reaction in the lung by macrophages in the alveoli walls? |
C5a & FcγRIII Probably also required for reaction induced by MC in the skin & linings of joints (synovia) |
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Activation of FcγRIII on MC induces their degranulation |
True |
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What is type III hypersensitivity known as? |
Serum sickness |
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What does serum sickness result from? |
Injection of large qualities of a poorly catabolised foreign Ag |
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Antiserum made by immunising _______ in pre-Ab era and used to treat ____________ ____________ |
horses; pneumococcal penumonia |
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What is antivenin? |
Serum from horses immunised with snake venom |
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What happens with serum sickness? |
Occurs after 7-10 days after injection of horse serum |
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What does the time period after which serum sickness sets in allow? |
IgG-switched primary IR against foreign Ag |
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Clinical features of serum sickness |
Chills Fever Rash (urticaria is a prominent feature) Arthritis Sometimes glomerulonephritis |
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How is MC degranulation triggered in this case? |
Ligation of cell-surface FcγRIII by IgG-containing IC |
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What does the onset of serum sickness coincide with? |
Development of Ab against soluble proteins in the foreign serum |
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What is the course of serum sickness? |
Ab development IC formation Fix C', bind to & activate leukocytes bearing Fcr/C'R Widespread tissue damage |
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What do the ICs cause? |
Clearance of the foreign Ag, so serum sickness is usually a self-limiting disease |
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When is pathological IC deposition seen? |
Ag persists as when an adaptive Ab response fails to clear the infecting pathogen e.g. subacute bacterial endocarditis, chronic viral hepatitis |
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What happens in these pathological situations? |
Pathogen continuously generates new Ag in presence of persistent Ab response, with formation of ICs IC deposition within small BV, with consequent injury in many tissues & organs |
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IC disease also occurs when _________ allergens provoke IgG rather than IgE Ab responses |
inhaled |
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What happens to a farmer's lungs who are repeatedly exposed to hay dust or mould spores? |
IC forms in alveoli walls Accumulation of fluid, protein & cells in alveolar wall Blood-gas interchange slowed Compromised lung function Lung lining can be permanently damaged |
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Hypersensitivity reactions are mediated by ____________ & _________ |
Th1 cells; CD8+ cytotoxic T cells |
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What is type IV hypersensitivity aka? |
Delayed-type hypersensitivity |
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How are DTH reactions mediated? |
Ag-specific effector T cells |
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What is the prototype DTH reaction? |
Tuberculin test |
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What is this reaction used determine in patients? |
Whether person has been previously infected with Mycobacterium tuberculosis |
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What happens in the Mantoux test? |
Small amounts of tuberculin Complex mixture of peptides & carbs derived from M. tuberculosis are injected intradermally |
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How would people have been previously exposed to it? |
BCG vaccine (attenuated form of M. tuberculosis) Infection |
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What happens in people who have been exposed to it after they receive the vaccine? |
Local T cell mediated inflammatory reaction evolves over 24-72hrs |
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List some Ag that induce DTH? |
Insect venom, mycobacterial proteins |
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What are the consequences of DTH? |
Local skin swelling: erythema induration cellular infiltrate dermatitis |
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What type of Ag mediate contact hypersensitivity? |
Absorbed into skin Haptens: poison ivy DNFB Small metal ions: nickel & chromate |
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What are the consequences of CH? |
Local epidermal reaction: erythema cellular infiltrate vesicles intraepidermal abscesses |
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What type of Ag mediate gluten-sensitive enteropathy (Celiac disease)? |
Absorbed by the gut Gliadin |
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What is the consequence of gluten-sensitive enteropathy? |
Villous atrophy in small bowel malabsorption |
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Stages in DTH |
Ag injected into subcutaneous tissue Processed by local APC Th1 effector cell recognizes Ag, releases cytokines which act on vascular endothelium Phagocytes recruited Visible lesion |
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Cytokines released & their effects |
IFN-γ and TNF-β. Stimulates expression of adhesion molecules on endothelium Increase local blood vessel permeability Allowing plasma and accessory cells to enter the site Swelling |
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How long do these phases take? |
Several hours Fully developed response appears 24-28hrs |
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Chemokines are also secreted. What effects are caused? |
Recruit macrophages to site of Ag deposition |
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IL-3/GM-CSF is also secreted. What effects are caused? |
Stimulate monocyte production by bone marrow stem cells |
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How do Th1 cells activate macrophages? |
Release of IFN-γ and TNF-α Kill macrophages & other sensitive cells through the cell-surface expression of the Fas ligand |
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What is allergic contact dermatitis? |
Immune-mediated condition caused by direct Ag contact with skin Caused by activation of CD4/8 T cells, depending on how Ag is processed |
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Describe the typical Ag that cause cutaneous hypersensitivity responses? |
Highly reactive small molecules that can easily penetrate intact skin, especially if they cause itching that leads to scratching |
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These chemicals then react with self proteins, creating ________________ complexes that can be processed to form _______________ complexes capable of being presented by MHC molecules and recognised by T cells as foreign antigens. |
hapten:protein;hapten:peptide |
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What are the 2 phases to a cutaneous allergic response? |
Sensitization Elicitation |
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What happens in the sensitization phase? |
Cutaneous Langerhans cells take up & process Ag Migration to regional lymph nodes T cells activated Production of memory T cells, which end up in the dermis. |
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What happens in the elicitation phase? |
Subsequent exposure to the sensitising chemical leads to Ag presentation to memory T cells in dermis, with the release of T-cell cytokines such as IFNγ and IL-17. |
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What does the release of cytokines & Ag presentation lead to? |
Stimulates the keratinocytes of the epidermis to release cytokines & chemokines which enhance the inflammatory response by inducing the migration of monocytes into the lesion and their maturation into macrophages & by attracting more T cells |
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What causes the rash produced by poison ivy? |
CD8 T cell response to a mixture of pentadecacatechols in the plant. |
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Pentadecacatechols |
Lipid-soluble chemicals that cross the cell membrane & modify intracellular proteins |
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What happens to the modified proteins? |
Generates modified peptides within cytosol Translocation to ER Delivered to cell surface-bound to MHC Class I CD8+ recognizes peptide Damage caused either by killing it or secreting cytokines like IFNγ. |
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Coeliac disease has the features of both an __________ ___________ & ______________________ |
Allergic response; autoimmunity |
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Coeliac disease
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Chronic condition of the upper small intestine caused by an IR directed at fluten |
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What is gluten? |
Complex of proteins present in wheat, oats & barley |
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What does elimination of gluten from the diet do? |
Restore normal gut function |
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What is coeliac disease characterised by? |
Loss of villi formed by the intestinal epithelium (a condition termed villous atrophy) Increase in the size of the sites in which epithelial cells are renewed (crypt hyperplasia). |
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What do these abnormal changes result in? |
Mature epithelial cells that cover the villi which normally absorb & digest food Severe inflammation of the intestinal wall Increased no. of T cells, macrophages & plasma cells in the lamina propria Increased no. of lymphocytes in the epithelial layer |
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Does coeliac disease show an extremely strong genetic predisposition? |
Yes More than 95% of patients expressing the HLA-DQ2 class II MHC allele |
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Most individuals expressing HLA-DQ2 do not develop coeliac disease despite the almost universal presence of gluten in the Western diet. What does this mean? |
Other genetic factors must make important contributions to susceptibility. |
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Autoimmunity features are detected in coeliac disease |
True |
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What are the autoantibodies directed against in all victims? |
Tissue transglutaminase |
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Is there evidence that these autoantibodies contribute to tissue damage? |
No |