Hypersensitivity Reactions Flashcards
What is hypersensitivity?
β An inappropriate immune response to non-infectious antigens that results in tissue damage and disese
How many types of hypersensitivity are there?
β 4
What is type 1 hypersensitivity?
β Immediate hypersensitivity
What is type 2 hypersensitivity?
β cytotoxic hypersensitivity
What is type 3 hypersensitivity?
β serum sickness and Arthus reaction
What is type 4 hypersensitivity?
β Delayed-type hypersensitivity
β contact dermatitis
Describe what happens in type 1 hypersensitivity?
β Type 1 results to being exposed to allergens in the environment
β the host generates an immune response characterised by the production of IgE antibodies
β The IgE antibodies become attached to immune cells called mast cells
β when someone is exposed to the allergen to which the IgE is specific the IgE is cross-linked and activates the inflammatory cells to release mediators causing inflammation
What type of conditions have type 1 reactions?
β Allergic rhinitis
β asthma
β anaphylaxis
β eczema
How can you induce immediate hypersensitivity?
β injecting an allergen onto the skin or by scratching the allergen onto the skin
How does the hypersensitivity reaction occur?
β If you have mast cells in the tissue that carry specific IgE
β the IgE will be cross-linked
β the mast cells are activated and release lots of inflammatory mediators that result in leakage of plasma and fluid into the surrounding tissues (wheal)
β vasodilation results in the flare response (erythema)
What is systemic anaphylaxis?
β Exaggerated response to an allergen
What occurs during systemic anaphylaxis?
β Someone is exposed to an allergen to which they are sensitised and develop a marked reaction to the allergen
β vasodilation and release of liquid into the tissue which causes edema
What is type II hypersensitivity caused by?
β an immune response generated against altered components of human cells
What is an example of type II hypersensitivity?
β people treated with penicillin
β drugs attach to the surface of RBCs
βthe attachment to the red cells is seen as an altered component
Describe how hypersensitivity type II occurs?
β a platelet or red cell is covered in a drug like penicillin
β the immune response recognises them as an allergen and generates an IgG response to that
β the red cell to which the drug is attached is coated by IgG
β this activates cells containing the IgG receptor causing activation of macrophages and activation of complement resulting in inflammation
What is an example of a type II response where IgG antibodies are directed at cell surface receptors?
β Myasthenia gravis
β Graves
Describe normal TSH function?
β pituitary releases TSH which acts on the thyroid and causes the release of thyroxine
β the levels of thyroxine in the blood cause negative feedback which reduces the TSH
What happens in Graves disease?
β Immune response is generated against TSH receptors
β this causes long term stimulation of the receptors which causes the thyroid to release thyroxine with no negative feedback
What happens in Myasthenia Gravis?
β There is an immune response directed against the post-synaptic receptors
β antibodies block or destroy nicotinic AcH receptors at the neuro-muscular junction
β this blocks nerve transmission resulting in paralysis
What type of hypersensitivity is haemolytic disease of the newborn?
β type II
Describe how haemolytic disease of the newborn occurs?
β if a rhesus negative mother has a rhesus positive child
β they can develop an immune response against the rhesus antigen
β during birth Rh+ fetal erythrocytes leak into maternal blood after breakage of the embryonic chorion which normally isolates fetal and maternal blood
β maternal B cells are activated by the Rh antigen and produce large amounts of anti-Rh antibodies
β during the second exposure (second pregnancy) the Rh antibody titer in the motherβs blood is elevated after first exposure
β Rh antibodies are small enough to cross the embryonic chorion and attack the fetal erythrocytes
Describe what happens during type III hypersensitivity?
β presence of a soluble antigen such as a vaccine (tetanus toxoid)
β there is an IgG response to the antigen
β because there are large amounts of antibody and antigen at the site of injection, immune complexes form
β immune complexes can activate the cells around the capillaries causing an inflammatory response and activating the complement
What is type III hypersensitivity also called?
β Arthus reaction/serum sickness
What do the immune complexes cause activation of?
β mast cells
Why does haemorrhage and purpura occur in type III?
β blood vessel permeability and blood flow are increased
β platelets accumulate leading to the occlusion of small blood vessels, haemorrhage and purpura
What is serum sickness caused by?
β large IV doses of soluble antigens
What happens during serum sickness and how does tissue damage occur?
β IgG antibodies produced form small immune complexes with the antigen in excess
β immune complexes are deposited in the tissues e.g blood vessel walls
β tissue damage is caused by complement activation and the subsequent inflammatory response
How is antivenom made?
β Injecting a horse with venom and collecting the serum
What can injecting people with horse immunoglobulin cause?
β Serum sickness
β nephritis if the immune complexes are deposited in the kidney
How does farmers lung happen?
β Farmers are exposed to hay
β hay has moulds in it which are inhaled
β they cause localised inflammation in the lung and immune complex reaction
β IgG and antigen gets complexed
What mold is found in sugarcane?
β actinomycosis
What type of a reaction can inhaling actinomycosis cause?
β type III reaction
What happens if you inhale actinomycosis?
β fibrosis, granulation and inflammation
β interstitial pneumonitis - non caseating granulomas
What are the resulting 3 diseases caused if antigens are given IV and where do the immune complexes deposit?
β Vasculitis - immune complexes deposit in the blood vessel walls
β Nephritis - immune complexes deposit in the renal glomeruli
β Joint spaces -immune complexes deposit in the joint spaces
What disease occurs if antigens are given subcutaneously and where do the immune complexes deposit?
β Arthus disease
β perivascular area
What disease occurs if antigens are inhaled and where do the immune complexes deposit?
β Farmers lung
β alveolar/capillary interface
What are the two forms of type IV hypersensitivity?
β related to the immune cells that are produced
βTH1 and TH2
What is TH1 associated with?
β response to intracellular bacteria
What is TH2 associated with?
β responses to worm infections
Describe how TH1 type IV delayed hypersensitivity to tuberculin happens?
β tuberculin stimulates TH1 cells to produce cytokines such as IFN gamma and IL-12 which stimulate macrophages to release cytokines and chemokines which recruit cells to the site of infection
β a granuloma is formed (tuberculin granuloma) which takes 2-3 days
What is the mantoux test?
β Inject an extract of dead tuberculin subcutaneously
β wait to see if there is a reaction within 2-3 days
Describe how TH2 delayed type hypersensitivity occurs?
β TH2 cells produce cytokines such as IL-4 and IL-5 which are important in IgE production and eosinophil recruitment
β this causes production of basic proteins, enzymes and cytokines
What is TH2 mediated hypersensitivity associated with?
β allergic contact dermatitis
What is the tuberculoid response?
β strong TH1 response to the presence of leprosy bacilli resulting in granuloma and DTH type response
How does IgE mediated hypersensitivity happen and what type is this?
β Ag induces cross-linking of IgE bound to mast cells and basophils with release of vasoactive mediators
β Type I
How does IgM or IgG mediated hypersensitivity happen and what type is this?
β Ab directed against cell surface antigens mediates cell destruction via complement activation or ADCC
β type II
How does Immune complex mediated hypersensitivity happen and what type is this?
β Ag-Ab complexes deposited in various tissues induce complement activation and an ensuring inflammatory response mediated by massive infiltration of neutrophils
β type III
How does cell mediated hypersensitivity happen and what type is this?
β sensitised Th1 cells release cytokiens that activate macrophages or Tc cells that mediate direct cellular damage
β Th2 cells and CTLs mediate similar responses
β Type IV
What are 4 allergens that cause systemic anaphylaxis?
β drugs
β serums
β venom
β peanuts
What are 3 allergens that cause acute urticaria (wheal and flare)?
β animal hair
β insect bites
β allergy testing
What are 2 allergens that cause allergic rhinitis?
β pollens
β dust mite feces
What are 3 allergens that cause asthma?
β Danders (cat)
β pollens
β dust mite feces
What are 6 allergens that cause food allergy?
β peanuts β tree nuts β shellfish β milk β eggs β fish
What is IgE used against?
β worms
How is IgE different to IgG?
β it has one extra domain in the heavy chain compared to IgG
What does IgE bind to on mast cells?
β FcΞ΅R1 receptor
What do IgE cells do to mast cells and inflammatory cells?
β pre-arms them to react in the presence of an antigen
β coats inflammatory cells and basophils
Describe allergen specific (pollen) IgE production?
β the first exposure to pollen causes activation of the immune response
β APC picks up pollen and takes it to the local lymph nodes where they activate immune cells
β they activate TH2 cells
β TH2 cells release IL-4 which induces B cells that have the same specificity to allergens to produce IgE
β the IgE is released in circulation on mast cells, ready for the next exposure to the allergen
What causes allergic sensitisation?
β Exposure to the allergen including dosage, timing, location of priming
β genetic pre disposition
How are allergens named?
β after the source organism and the order they were discovered
What happens in high dose vs low dose exposure to an allergen?
β high dose - tolerance
β low dose - sensitisation
What is the link between filaggrin and atopic dermatitis?
β filaggrin granules form a barrier on skin
β when it is defective atopic dermatitis is greater
What makes a dendritic cell pro-allergic?
β a protein called TSLP which can switch DC to a pro-allergic state
β TSLP : thymic stromal lymphopoietin
What do activated mast cells release?
β releases its granules (histamines and leukotrienes)
What are the two phases of an allergic response?
β Early and late phase
What is the early phase mediated by?
β mast cells
What is the late phase mediated by?
β T cells
What happens during the early response?
β activation of mast cells and release of mediators
Describe what happens during primary exposure to an allergen?
β Sensitisation
β dendritic cells present antigens to the T cells
β Activated T cells produce IL-13 and IL-4
β this causes B cells to release IgE
β IgE lines the mast cells
What happens during secondary exposure to an allergen?
β The mast cells release histamine and lipid mediators
β T cells recruit eosinophils and other mast cells
What happens in an acute allergic reaction?
β Wheezing
β Urticaria
β Sneezing, rhinorrhoea
β conjunctivitis
What happens in a chronic allergic reaction?
β Further wheezing
β sustained blockage of the nose
β Eczema
What is the function of histamine?
β Increases vascular permeability
β causes smooth muscle contraction
What is the function of Leukotrienes?
β increases vascular permeability
β causes smooth muscle contraction
β stimulates mucus secretion
What is the function of Prostaglandins?
β Chemoattractants for T cells, eosinophils and basophils
What does IL-4 and IL-13 promote?
β TH2
β IgE
What does TNF alpha promote?
β Promotes tissue inflammation
What three substances are released during the early phase of an allergic reaction?
β Histamine
β leukotriene
β prostaglandins
What does mast cell activation and granule release cause in the GI tract?
β Increased fluid secretion and increased peristalsis
β expulsion of GI contents (vomiting & diarrhoea)
What does mast cell activation and granule release cause in the airways?
β Decreased diameter and increased mucus secretion
β congestion and blockage of airways (wheezing), coughing and phlegm
β swelling and mucus secretion in nasal passages
What does mast cell activation and granule release cause in the blood vessels?
β Increased blood flow, increased permeability
β increased fluid in tissues causing increased lymph to lymph nodes, increased cells and proteins in tissues, increased effector response in tissues
Where are eosinophils located and where are they recruited to?
β located in tissues
β recruited to sites of allergic reactions
What do eosinophils express upon activation?
β FcΞ΅R1
What are the two effector functions of eosinophils?
βRelease highly toxic granule proteins and free radicals upon activation to kill microorganisms/parasites and cause tissue damage in allergic reactions
βSynthesise and release prostaglandins, leukotrienes and cytokines in order to amplify the inflammatory response by activating epithelial cells and recruiting leukocytes
What is the late phase of the allergic reaction dependent on?
β allergen dose
What is chronic allergic inflammation caused by?
β TH2 cells
What is asthma?
β a state of reversible bronchial hyper reactivity resulting from a persistent inflammatory process in response to a number of stimuli in a genetically susceptible individuals
What are the two types of asthma?
β atopic and non-atopic
What are the 4 causes of asthma?
β Occupational
β exercise induced
β nocturnal asthma
β post-bronchiolitic wheeze
What are the 3 characteristics of allergic asthma?
β Episodes of wheezy breathing
β narrowing of the airways
β rapid changes in airway obstruction
What does the acute response to asthma cause and within what timeframe?
β occurs within seconds of allergen exposure
β results in airway obstruction and breathing difficulties
What is acute asthma caused by?
β allergen induced mast cell degranulation in the submucosa of airways
What is the chronic response to asthma caused by?
β activation of eosinophils, neutrophils, T cells and other leukocytes
What does the chronic response to asthma cause?
β Airway remodelling, permanent narrowing of the airways and further tissue damage
What are the 6 treatment options for asthma?
β Inhibit effects of mediators on specific receptors - antihistamines
β inhibit mast cell degranulation - mast cell stabilisers
β inhibit synthesis of specific mediators - lipoxygenase inhibitors
β steroids
βbronchodilators
β immunotherapy
What is an example of a lipoxygenase inhibitor?
β montelukast
What is an example of a mast cell stabiliser?
β chromoglycate
What effect do steroids have on asthma?
β act directly on DNA to increase transcription of anti-inflammatory mediators such as IL-10 and decrease transcription of pro-inflammatory mediators
What is a steroid used to treat asthma?
β prednisolone
What is an example of a bronchodilator?
β Salbutamol
