Lecture 2 - Type 1 Hypersensitivity (allergy) Flashcards
What is the brief process of adaptive immune repsonse for allergens?
APC engulfs allergen/ antigen
APC processes via exogenous pathway (phagolysome) then antigen expressed to CD4+ naive T cells via MHC II molecules stimulating T Helper 2 cells to be produced
What do T Helper 2 cells produce?
B cells that make IgE and IgG
Eosinophils
Mast cells
What T helper cell is importnat in allergies?
T helper 2 cell
What immunoglobulin is the main immunoglobulin in Type I hypersensitivity (allergic) reactions?
IgE
How long do immediate type I hypersensitivity (allergic) reactions take to work?
Less than 30mins
What are allergens?
Environmental non-infectious antigens that wouldn’t normally lead to an immune repsonse
What is the brief process of Type I hypersensitivity reactions (allergies)?
Abnormal adaptive immune response (T helper 2 response leading to IgE production)
Mast cell activation (sensitised by IgE)
What are some seasonal allergens?
Tree
Grass
Pollens
(Cause allergic rhinitis)
What are some perennial exposures to allergens?
House dust mite
Animal dander
Fungal spores
What are some accidental exposures to allergens?
Insect venom
Penicillin (medicines)
Chemicals (latex)
Foods - milk, nuts and shell fish
What groups of people are allergens most common in?
More developed urban homes
What type of adaptive immune response is most common in populations in developing countries, withi large family sizes, rural homes, low Abx use and poor sanitation?
TH1 response
What type of immune response is more common in developed countries, with small family homes, high antibiotic use and good sanitation compared to its poor counterparts?
Abnormal abnormal TH2 repsonse leading to type 1 hypersensitity
What is the hygiene hypothesis for allergies?
Being exposed to microbes in early life decreases risk of allergies
Children exposed to animals, pets and microbes int he early postnatal period appear to be protected against certain allergic diseases
What is the biodiversity hypothesis for allergies?
Western lifestyle devices alteration of the symbiotic relationships with parasites and bacteria leading to dysbiosis of the micro biome at the gut
What is the main cell following T helper 2 cells in allergic reactions?
Mast cells
What are the steps to sensitisation of mast cells in allergic reactions?
Antigen penetrates mucosal barrier
DENTRITIC cell engulfs and presents to T helper 2 cells via MHC class II cells
Leads to production of antigen specific IgE
IgE binds to mast cells so theres now primed mast cells
What happens once IgE have cross linked to mast cells?
Mast cells degranulate releasing:
-histamines
-chemokines
-leukotrienes
-prostaglandins
What are the 3 main effects of granule contents like histamines, chemokines, leukotrienes and prostaglandins?
Increased vascular permeability
Vasodilation
Bronchial constriction
Where are mast cells located?
Most mucosal and epithelial tissues (GI, skin, resp epitehlium)
Connective tissue surrounding blood cells
What are sine examples of mast cell mediators?
Tryptase
Histamine
Leukotrienes
Platelet-activating factor
What causes urticaria?
Mast cell activation within the epidermis
What mediators are released by mast cells in urticaria?
What effect does this have?
Histamine
Leukotrienes/cytokines
Vasodilation
Inc vascular permeability (fluid int he wheels)
What can prolonged exposure to allergic reactions leading to urticaria cause?
Atopic dermatitis
Eczema
What is angiodema?
Mast cell activation/degranulation in the deep dermis or subcutaneous/submucosal tissue
What mediators are released by mast cells in angioedema?
What effect to these have?
Histamine
Bradykinin
Inc vasc permeability
Vasodilation
Why can angioedema be very dangerous?
Angiodema in the upper airways can be deadly
What is anaphylaxis?
Most serious form of Type 1 hypersensitivty reaction
Systemic activiation of mast cells leading to increased vascular permeability, vasodilation and bronchiole constriction
How can a patient present with angiodema?
Hypotension (vasodilation)
Cardiovascular collapse
Generalised urticaria
Angiodema (vasodilation)
Breathing problems (bronchial constriction)
What are the 2 methods of treating type 1 hypersensitivity reactions?
Treat the abnormal immune response to the allergen (TH2 repsonse)
Mast cell activation interruption
What are some drugs that can be used to treat type I hypersensitivity reactions?
Omalizumab (anti IgE)
Mepolizumab (anti-IL5)
What are some drugs to that act against mast cells?
Antihistamines (Block H1 receptors)
Leukotriene receptor antagonists
Corticosteroids
What is an example of leukotriene receptor antagonist?
Monteleukast
What is the definition of desensitisation or immunotherapy?
Administration of increasing doses of allergen extracts over a a period of Years given too patients by injection or drop/tablets under the tongue
How do you treat anaphylactic shock?
Intramuscular adrenaline injection
How does intramuscular injection of adrenaline treat anaphylactic shock?
Reverses peripheral vasodilation and reduces oedma and alleviates hypotension
Reduces airway obstruction/bronchospams
Binds to SAN icnnrneasing force of myocardial contraction
Inhibts mast cell activation
Where is an IM of adrenaline get administered in anaphylactic shock?
Lateral aspect of thigh
May need to be administered multiple times
