Allergies Flashcards
What is an allergy?
disease following a response by the immune system to an otherwise innocuous antigen
what is a hypersensitivity?
harmful immune responses that produce tissue damage
What is the immun reactant in type I hypersensitivity?
IgE
Describe the antigen in in type I hypersensitivity
Soluble
What is the effector mechanism in in type I hypersensitivity?
Mast cell activation and degranulation
What is an example of in type I hypersensitivity
Allergy
Asthma
Describe the mediation of allergy by antibodies
IgE mediated and always occurs on secondary exposure to an allergen, so an initial exposure event has always taken place
Describe the normal serum levels of IgE and the reason for this?
very low
sticks to mast cells
When does allergy occur?
When IgE triggers mast cell degranulation
Where is IgE produced?
produced by plasma B cells in lymph nodes or locallat sites of inflammation
Where is IgE located?
in tissue, bound to mast cell surface due to high affinity of IgE receptor FceRI
What cells fabour IgE responses>
CD4+ T cells of the Th2 phenotype that produce IL4 cytokines favour IgE responses
What do CD8 cytotoxic cells produce?
- IFNgamma
- TNFalpha
Target cell lysis
What do CD4 Th1 cells produce?
- IFNgamma
- GM-CSF
- TNFalpha
macrophage activation
What do CD4 Th2 cells produce?
- IL4
- IL5
B cell activation
What are some common sources of allergens?
- inhaled material
- plant pollens
- house dust mite
- injected material
- venoms
- vaccines
- drugs
- ingested material
- food
- orally administered drugs
- contacted materials
- plant lkeaves
- industrial products from plants
- synthetic chemicals in industrial products
- metals
What are the main features of inhaled allergens?
- protein - T cell response
- Enzymatically active
- Low dose - IL4 response = CD4 T cells
- small size
- highly soluble
- stable - survive dessication
What is IgE thought to be cruical against?
host defence against parasites
What is the major allergen in house dust mite?
Der p 1
How does Der p 1 work?
can cleave tight junctions between epithelial cells allowing access
taken up by dendritic cells, presented to T cells, which becomes Th2 and cause B cells to secrete IgE
What is the most important factor in determining the symptoms of an allergen?
location and distibrution
What is allergic asthma?
- bronchial constriction
- increased secretion of fluid and mucus trapping inhaled air
- chronic inflammation may follow with the continued presence of Th2 cells, eosinophils and neutrophils
Draw a graph showing the FEV (air expulsion capacity) in an asthmatic response
What usually occurs in a skin allergy?
rashes
What is wheal and flare a result of?
vasodilation after mast cell degranulation causing localised redness
What happens approx. 8 hrs after a skin allergy occurs?
oedema at the site due to influc of lymphocytes and other leukocytes attacted by chemokines
What do ingested allergens cause?
- Activation of GI Mast cells results in transepithelial fluid loss and smooth muscle contraction: diarrhea and vomiting
- If allergen enters blood stream, generalised disseminated rash, Urticaria, (hives).
- In severe cases of food allergy, eg nuts and shellfish, life threatening generalised anaphylaxis and cardiovascular collapse may occur
What are the main chemical mediators involved in allergic response?
- lipids
- toxic mediators
- cytokines
- enzymes
What is the effect of lipids in allergic response?
- Prostaglandins; increased vascular permeability, increased body temperature.
- Platelet activating Factor; increased adhesion between endothelium and neutrophils.
- Leukotrienes, attract and activate neutrophils, increased vasc permeability
What is the effect of toxic mediators in allergic response?
- Histamine; increased vascular permeability, and promotes movement of fluid from the vasculature by constricting vascular smooth muscle.
- Heparin, inhibits coagulation
What is the effect of cytokines in allergic response?
- IL-4, IL-13; amplify Th2 response
- IL-3, IL-5, GM-CSF; promote eosinophil activation and production
- TNF-alpha; pro-inflammatory, activates endothelium
- Chemokine MIP-1alpha; attracts macrophages and neutrophils
What are the enzymes involved in allergic response?
- Tryptase
- Chymase
- Cathepsin G
- Carbopeptidase
- Remodel connective tissue matrix
What are the two main types of treatment currently used for treatment of allergy?
densensitisation and blockade of effector pathways
How does desensitisation and blackade work?
- Aim to shift response from IgE dominated to IgG dominated
- Patients injected with escalating doses of allergen, gradual shift from Th2 to Th1 T cells.
- Potential risk of inducing anaphylaxis!
- Anti-histamines, H1 receptor blocking.
- Topical or systemic corticosteroids to supress chronic inflammation in asthma and rhinitis
What should severe anaphylaxis be treated with?
epinephrine (adrenaline) injection
What is a key defence in helminth expulsion?
IgE
