Hypersensitivity reactions (asthma and allergy) Flashcards
How is hypersensitivity classified
- Type 1: Immediate hypersensitivity
- Type 2: Cytotoxic hypersensitivity
- Type 3: Serum sickness and Arthus reaction
- Type 4: Delayed-type hypersensitivity, contact dermatitis
Describe how type 1: Allergy mechanism works
- Mediated by IgE
- There is an interaction between mast cells, IgE and the allergens
- causes degranulation and releases cytokines for an allergic response
- Consequences are allergic rhinitis, Asthma and anaphylaxis
Describe what happens with systemic anaphylaxis
- Severe localised oedema
- Vey progressive reaction
- Occlusion of airways and causes asphyxia
- Treated with adrenaline (Epi-pen)
Describe how type 2 hypersensitivity mechanism works
- Mediated by IgG (anti-drug antibodies)
- Drug binds red blood cells or platelets and antibodies bind to the drug
- Antibody-bound cells are cleared by macrophages and form complements
- Leads to inflammation and disease
Explain how graves disease is an example of Type 2 hypersensitivity
- IgG antibodies are made against the TSH receptor
- IgG blocks receptor binding which results in the inhibition of the negative feedback cycle
- Excess thyroid hormone is produced
Give some other examples of type 2 hypersensitivity
- Myasthenia gravis
- Newborn haemolytic disease
Describe how type 3 hypersensitivity mechanism works
- Mediated by IgG
- A soluble antigen comes in contact with antibodies
- IgG and antigen form immune complexes
- Immune complexes cleared by phagocytes
Describe how serum sickness is type 3
- Caused by large
intravenous doses of
soluble antigens (e.g.
drugs) - IgG antibodies produced
form small immune
complexes with the antigen
in excess. - Immune complexes
deposited in tissues e.g.
blood vessel walls. - Iissue damage is caused
by complement activation
and the subsequent
inflammatory responses
Describe how farmers lungs is an example of type 3
- Hay or grain dust is inhaled into farmers lungs
- Causes a type 3 hypersensitivity reaction
- Inflamed lungs
Describe how type 4 hypersensitivity mechanism works
- T-cell mediated response to antigens
- T cell gets activated and activates macrophages which release chemokine, cytokine and cytotoxins
Explain the time-delayed nature of type 4 hypersensitivity
- Takes time for T cell activation to happen and differentiate into effector cells to carry out the response
List some examples of type 4 hyper sensitivity reactions
- Mantoux test
- Tuberculoid leprosy
- Contact dermatitis
- Poison ivy
Describe the characteristic of the IgG antibody
- First line of defence against worms
- Binds FcεR1 receptor on mast cells
- Pre-arms mast cells to react when in the
presence of antigen
Describe the allergen-specific IgE production model
- There is initial exposure to pollen
- IL-4 drives B cells to produce IgE in response to pollen antigens
- Pollen specific IgE binds to mast cells
What factors determine allergen sensitivity
- Nature of allergen
- Dosage of Allergen
- Timing
- Location of priming
- Role of pro-allergic dendritic cells and cytokines
- genetic predisposition to allergy
What are some characteristics of common allergens
- Examples include: dust mites, pollens and cockroaches
- Named after the source organism and the order of discovery
- Allergens have common functionalities such as proteases
- Normally received in small doses
- High-dose exposure may lead to tolerance
What are filaggrin and atopic dermatitis
- Filaggrin links skin integrity
and allergy - When it is defective atopic dermatitis is greater
- This is due to the access for allergens
What makes dendritic cell pro-allergic
Not Known but One Candidate Protein is TSLP This may switch DC to a ‘pro- allergic’ state
What happens to mast cells when activated by allergens
- Resting mast cell contains granules containing histamine and other inflammatory mediators
- Multivalent antigen cross-links bound IgE antibody causes release of granule contents
What causes early and late phase allergic response
- Early phase is immediate and mediated by mast cells
- The late phase is delayed and is mediated by T cells
What effector mediators are produced by mast cells in the early phase
- Histamine - Increases vascular permeability and cause smooth muscle contraction
- Leukotrienes - increase vascular permeability, smooth muscle contraction and stimulate mucus secretion
- Prostaglandins - chemoattractant for T cells, eosinophils and basophils
What effector mediators are produced by mast cells in the late phase
Cytokines:
- IL-4 and IL-13 - promotes Th2 and IgE
- TNF-a - promotes tissue inflammation
what are the effects of mast cell activation the GI tract
- Increased fluid secretion
- Increased peristalsis
- Causes expulsion of GI tract contents
What are the effects of mast cell activation on the airways
- Decreased diameter
- Increased mucus secretion
- Congestion and blockage of airways
- Swelling and mucus secretion in nasal passages
What are the effects of mast cell activation on blood vessels
- Increased blood flow
- Increased permeability
- Increased fluid in tissues causing increased flow of lymph to lymph nodes
- Increased cells and protein in tissue
- Increased effector response in tissues
what are the effector function of eosinophils
- Release highly toxic granule proteins and free radicals upon activation to kill microorganisms/par sites and cause tissue damage in allergic reactions.
- Synthesise and release prostaglandins, leukotrienes and cytokines in order to amplify the inflammatory response by activating epithelial cells and recruiting leukocytes.
Describe the late phase of the IgE mediated allergic response
- Late-phase reaction is dependent on
allergen dose - Continued synthesis and release of
inflammatory mediators - Chronic allergic inflammation caused by Th2 cells i.e. a type IV hypersensitivity
reaction
what is Asthma
A State of reversible bronchial hyper reactivity resulting from a persistent inflammatory process in response to a number of stimuli in a genetically susceptible individual
List some characteristics of asthma
- episodes of wheezy breathing
- narrowing of the airways
- rapid changes in airway obstruction
- severity varies
- slight wheeziness to asthma attack
common allergens causing asthma include:
- pollen
- HDM
- plants
- some foods
Describe the acute response to 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 the airways
Describe the chronic response to allergic asthma
- chronic inflammation of the 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
how can we treat asthma
- inhibit effects of mediators on specific receptors: anti-histamine (block the histamine H1 receptor)
- inhibit mast cell degranulation: mast cell stabilizer (e.g. chromoglycate)
- inhibit synthesis of specific mediators: lipoxygenase inhibitors (e.g montelukast)
