WK 11- HYPERSENSITIVITY Flashcards
What is a hypersensitivity reaction
Occurs when a host becomes sensitised to an antigen and develops and inappropriate or excessive immune response against that antigen resulting in adverse effects upon second presentation of that Ag
What are the 2 phases of a hypersensitivity reaction
Sensitisation stage-> this is when the body first encounters the antigen and primes B cell to develop IgE Ab
Effector stage-> this occurs on second encounter to the Ag and results in release of chemical mediators that produce the classical allergic reaction symptoms
What are the 4 types of hypersensitivity
- Type 1/Immediate Hypersensitivity
- Type 2/Ab mediated cytotoxic hypersensitivity
- Type 3/immune complex hypersensitivity
- Type 4/Delayed-type hypersensitivity
Describe the pathogenesis of the sensitisation phase of type 1 hypersensitivity
- Ag enters body and is collected by DC and taken to the lymph node
- In the lymph the APC presents Ag to naive T cells-> if the APC also has a costimulatory molecule it will cause the T cell to turn into a Th2 cell
- The Th2 cells is now primed and will release IL-4 that binds to the Fce region of the mast cell
Describe the pathogenesis of the effector phase of type 1 hypersensitivity
- The mast cell is now primed with IgE
- on second exposure, the Ag will bind to the IgE molecule attached to mast cell and cross linking will occur
- Cross linking will cause degranulation of the mast cell and cause release of mediators like histamine, heparin, serotonin, chemotactic factors-> these cause the typical allergic reaction symptoms
Describe the symptoms that occur in type 1 hypersensitivity and how they occur
Angioedema: due to increased permeability and vasodilation from histamine
Hives: increased permeability
Airway constriction: bronchoconstriction via histamine
Diarrhoea: increased goblet cell activation
Redness: increased vasodilation
Itching: increased permeability and stimulation of nerve endings
Increased mucous production: increased activation of goblet
What is anaphylaxis
Occurs when the reaction becomes systemic in a sensitisation stage-> can be life threatening
- the extent of the anaphylaxis is determined the amount of IgE
- Hypotension= because of increased vasodilation
- SOB= bronchoconstriction
- Tachycardia/abnormal heart= because of increased workload on heart
- Urticaria=increased vascular permeability
What are the common treatments used to treat allergies
Anaphylactic reactions: adrenalin which stimulates reformation of endothelial tight junctions, relaxation of bronchial smooth, heart Asthma: Anti-IgE therapy for poorly controlled asthma, bronchodilators, avoidance of allergen, preventative and maintenance therapy, thermo bronchoplasty (bronchoscopy procedure with laser therapy to hypertrophied airway) Allergies: Allergen desensitisation restores ability to tolerate allergen, escalating doses, change in Ig class for IgE to IgG and Treg induction→ if you know what the allergy is, inject tiny amounts of allergen into skin and allow immune system to become desensitized (switch T cell from Th2 to Treg cell)- can be life threatening if not properly done and takes a long time to work
What is allergic asthma
Ag activates T cell->T cell activation of B cell (by IL-4, IL-13)→ activated B cell can release IgE ab against aeroallergen→IgE will bind to aeroallergen and mast cells on second exposure and cause degranulation of cells that results in release of immune mediators→ cause early response/acute phase (bronchospasm, oedema, airflow obstruction) and late/chronic response (airway inflammation and obstruction, airway hyper-responsiveness)
What are the 2 phases of allergic asthma
Acute: allergen can travel to the bronchi and cause stimulation of mast cells, leading to rapid smooth muscle constriction (bronchoconstriction), increased vascular permeability and mucous production leading to airway obstruction and recruitment of cells from circulation
Chronic: Th2 chronic inflammation that can occur in the absence of an allergen-> triggered by cytokines and eosinophil-> causes a build up of mucous and remodelling of the airways
What is airway remodelling
Wall of airway in asthma is thickened by oedema, cellular infiltration, increased smooth muscle mass and glands→ with increasing severity and chronicity remodelling occurs leading to fibrosis of the airway wall, fixed narrowing of the airway and reduced response to bronchodilators
What is type 2 hypersensitivity caused by
it is antibody mediated- occurs when Ab (IgG or IgM) react with fixed Ag on foreign cells and cause cellular destruction of the foreign cell
What are the 3 ways by which type 2 hypersensitivity causes cell damage
Opsonisation= Ige Ab coats a cells with C3b–> this attracts phagocytes that have receptors for C3b (or will bind directly to C3b) and phagocytose the particle
Ab dependent cellular cytotoxicity= Ab acts as an opsonin and will bind to an Ag, an NK cell will then bind to the Fc portion of the Ab and form a complex that will release cytotoxic granules (perforin, grazymes, granulysin)
Complement mediated lysis= Ab can bind to cell and act as an opsonin by forming a bridge between an Ag and a complement (C3a, C4a and C5a)- cause chemotaxis, mac formation and causes neutrophils to release cytotoxic granules that cause cell lysis
What are some classical examples of type 2 hypersensitivity
Haemolytic disease of the newborn, graft vs host disease, autoimmune thrombocytopenia, INCOMPATIBLE BLOOD TRANSFUSION
What is the cause of type 3 hypersensitivity
Ab (normally IgG) willl bind to a soluble ag and form an immune complex-> immune complex will attract complement and activate the classical pathway-> will cause recruitment of phagocytic cells that will remove insoluble complexes/those bound to RBC
-the soluble complexes (when they deposit) cause acute inflammation and tissue damage (often in BV, joints, glomerulus)
