Allergy And The Mechanisms Of Hypersentivity Flashcards
What is hyposensatvity?
An inappropriate immune response to non-infectious antigens that results in tissue damage and disease
What are the four type of hypersensitivity?
Type 1- immediate hypersensitivity
Type 2 - cytotoxic hypersensitivity
Type 3 - serum. Sickness and Arthur’s reaction
Type 4 - 44delayed-type hypersensitivity, contact dermatitis
What occurs in type 1 hypersensitivity (allergy)?
A immune reactant - IgE
Antigen - soluble antigen, eg. Allergen
Effector mechanism - mast cell activation and degranulation causing inflammation
What are some examples of type 1 hypersensitivity?
Allergic rhinitis
Asthma
Anaphylaxis
What is the prick test?
Test the allergic reaction by injection of antigen
And seeing what the immune response reacts to
Wat is systemic anaphylaxis?
A progressive inflammation
Severe loss of function
Progressive anaphylactic shock
What occurs in type 2 hypersenstivity?
Penicillin modifies rote is on human erythrocytes to create foreign epitopes - new areas antibodies can bind too.
Immune reactant - igG or anti drug antibodies directed at cell surface receptors
Antigen - drug ingested or a modified internal protein
Effector mechanism - antibody bound cells are cleared by complement + ffcgR+ cells such as macrophages - uncontrollable activation or blocking receptor function
What are some examples of type 2 hypersensitivity?
Some drug allergies
- eg. Penicillin,
- eg. Graves’ disease ,
- eg. myasthenia gravis (antibodies block or destroy nicotinic acetylcholine receptors at the junction between the nerve and muscle
- eg haemolytic disease of newborn
How can haemolytic disease of newborn occur?
- During fetal erythrocytes leak into maternal blood father breakage of the embryonic chorion
- Maternal B cells are activated by the Rh antigen an produce a large amount of antibodies
- Rh antibody titer in mothers blood is elevated after first exposure
- Rh antibodies are small enough to cross the embryonic chorion and attack the fetal erythrocytes
What occurs in type 3 hypersensitivity (serum sickness)?
Immune reactant - igG
Antigen - soluble antigen
Effector mechanism - igG and soluble antigen form immune complexes, which are cleared by phagocytosis
What are examples of type 3 hypersensitivity?
Arthur’s reaction following tetanus vaccination
Serum sickness
Farmers lung
What occurs during Arthur’s reaction?
- Local immune complex formation causes Activate mast cells to release inflammatory mediators
- Inflammatory cells invade the site and blood vessels permeability and blood flow are increased
- Platelets also accumulate, leading to occlusion of the small blood vessels, haemorrhage, and the appearance of purpura
What is serum sickness?
Caused by large doses of soluble antigens (drugs)
IgG antibodies produced from small immune complexes with the antigen in excess
Immune complexes deposited in tissues
Tissue damage is caused by complement activation an the subsequent inflammatory responses
What determines the pathology of type 3 hypersenstivity?
Antigen dose and route of delivery
What occurs in type 4 hypersenstivity (delayed type)?
Immune reactant - Th1, Th2 (antigen specific)
Antigen - soluble antigen
Effector mechanism - eosinophil activation (Th2), macrophage activation (Th1)
What are some examples of type 4 hypersensativity?
Tuberculin reaction
Allergic contact dermatitis
Describe what happens in type 4 hypersenstivity
Antigen is injected into subcutaneous tissue and processed by local antigen presenting cells
Th1 effector cell recognises antigen and releases cytokines that act on vascular endothelium
Recruitment of phagocytes and plasm to site of antigen injection causes visible lesion
What test s used to diagnose type 4 hypersensativity?
Mantoux test
Define a allergy (type 1 hypersenstivity)
Disease following a response by the immune system to an otherwise innocuous antigen
What is IgE?
First line f defence against worms
Bin FcR1 receptor on mast cells
Pre-arms mast cells to react when in the presence of antigen
Describe the simple model of allergen specific IgE production
First exposure to pollen
IL-4 drives B cells to produce IgE in response to pollen antigens
Pollen specific IgE binds to mast cells
What causes allergic sensitisation?
Exposure to allergen is critical
Role of pro-allergic dendritic cells and cytokines
Genetic predisposition to allergy
What are features of inhaled allergen that may promote the priming of Th2 cels that drive IgE responses?
Protein
Enymatically active
Low dose
Low molecular weight
Highly soluble - readily elated from particle
Stable - allergen can survive in desiccated particle
Contains peptides that bind host MHC class 2 - required for T cell priming
What makes a dendritic cell pro-allergic?
Not known
One candidate protein is RSLP - may switch DC to pro-allergic state
What is the role of filaggrin in allergens?
Flaggrin links skin integrity and allergy
Defective atopic dermatitis is greater and there are no flaggrin granules
What is the structure of a resting mast cell?
Contains granules containing histamine and other inflammatory mediators
What is the structure of a activated mast cell?
Multivalent antigen cross-inks bound IgE antibody, causing release of granule continents
What mediates thee early and late phases of the allergic response?
Early educated by mast cells
Late response educated by T cells
What occurs during the acute allergic response?
Primary allergen exposure occurs and causes IgE production
After second exposure
What occurs during the chronic allergic reaction?
Primary allergen exposure occurs and causes IgE production
After second exposure
What are the effector mediators produced by mast cells in the early phase?
Histamine - increase vascular permeability and cause smooth muscle contraction
Leuktrienes - increase vascular permeability and cause smooth uncle contraction and stimulates mucus secretion
Prostaglandins - chemoattractants for T cells eosinophils and basophils
What are the effector educators produced by mast cells in the late phase?
Cytokines
- IL-4, IL-13 - promotes Th2 and IgE
- TNF-a - promotes. Tissue inflammation
What is the effect of mast cell activation in the GI tract?
Increased fluid secretion, increased peristalsis
Expulsion of GI tract contents
What is the effect of mast cell activation in the airways?
Decreased diameter, increased mucus secretion
Congestion and blockage of airways
Swelling and mucus secretion in nasal passages
What is the effect of mast cell activation in blood vessels?
Increased blood flow, increased permiability
Increased permeability
Increased fluid in tissues means more flow of lymph to lymph nodes
Increased cells and proteins in tissues means Increased effector response in tissues
What are eosinophils?
Located in tissues
Recruited to sites of allergic reactions
Express FceRI upon activation
What are the 2 effector functions of eosinophils?
- Release toxic granule proteins and free radicals upon activation to kill parasites and cause tissue damage in allergic reactions
- Synthesis no release prostaglandins, leukotrienes and cytokines in order to amplify the inflammatory response by activating epithelial cells and recruiting leukocytes
What cels cause chronic allergic inflammation?
Th2
What does the late phase of the IgE mediated allergic response depend on?
Allergen dose
Continued synthesis and release of inflammatory mediators
What is asthma?
A state of reversible bronchial hyper-reactvity resulting from persistent inflammatory process in response to stimuli in a genetically susceptible individual
What are examples of non-atopic asthma?
Occupational
Excerise induced
Nocturnal asthma
Post-bronchiolitic wheeze
What are the characteristics of allergic asthma?
Episodes of wheezy breathing
Narrowing of airways
Rapid changes in airway obstruction
Severity varies
what occurs in the acute response of allergic asthma?
Occurs within seconds of allergen exposure
Results in airway obstruction and breathing difficulties
Caused by allergen-induced mast cell degranulation in the submucosa of airways
What occurs in the chronic is response of allergic asthma?
Chronic inflammation of airways
Caused by activation of eosinophils, neutrophils, T cells and other leukocytes
Mediators released by these cells cause airway remodelling, permanent narrowing of the airways and further tissue damage
What is the treatment of allergy in the clinic?
Steroids - act directly on DNA to increase transcription of anti-inflammatory mediators and decrease transcription of pro-inflammatory mediators
Broncholators - reverse acute effect of allergy on airways
Immunotherapy - reverses the sensitisation to allergen by means of tolerating exposure
Inhibit effects of mediators on specific receptors - anti histamine
Inhibit mast cell degranulation - mast cell stabiliser
Inhibit synthesis of specific mediations - lypoxygenase inhibitors
