Allergies Flashcards
Define allergy?
- Disease following a response by the immune system to an otherwise innocuous antigen.
Define Hypersensitivity
Harmful immune responses that produce tissue damage
What are the different types of hypersensitivity reactions and the immune reactant involved?
Type 1 - IgE.
Type 2 - IgG.
Type 3 - IgG.
Type 4 - Th1 cells, Th2 cells and cytotoxic T lymphocytes
Describe how allergy is mediated
It is IgE mediated and always occurs on secondary exposure to an allergen. So initial exposure event has always taken place. Allergy occurs when IgE triggers Mast cell degranulation
Describe the production of IgE antibodies
They are produced by plasma B cells in lymph nodes, or locally at the site of inflammation
Where is IgE located?
Mostly in tissue bound to mast cell surface through high affinity IgE receptors
What type of cells favour IgE responses?
CD4+ T cells of the Th2 phenotype that produce IL4 cytokines. Th2 T cells also force B cells to switch the isotype of theduce Ig they secrete from IgM to IgE
What does CD4 Th1 cells produce and what does this cause?
They produce TNF alpha, interfuron gamma and GM-CSF which cause macrophage activation
What does CD4 Th2 cells produce and what does this cause?
IL4 and IL5 which causes B cell activation.
What doe CD8 cytotoxic T cells produce?
Interferon gamma and TNF alpha which target cell lysis
What are some common allergens?
Inhaled materials - Pollen and house dust mites.
Injected materials - Wasps or drugs.
Ingested materials - Food or oral drugs
Contacted materials - Plant leaves, chemicals and metals
Describe the function of Der p and how it triggers an immune response
It is a major allergen in feces of house dust mites and can cleave tight junctions between epithelial cells in the airway. Der p 1 is taken up by dendritic cells, present to T cells which then become Th2 and cause B cells to secrete IgE
Describe what occurs in allergic asthma?
- Bronchial constriction, increased secretion of fluid and mucus, trapping inhaled air.
- Chronic inflammation may then occur with continued presence of Th2 T cells, eosinophils and neutrophils
Describe what occurs with a skin allergy?
- Allergens entering the skin site causes rash. Wheal and flare first appears within mins due to vasodilation after mast cell degranulation. After 8 hours more diffuse oedema at the site due to influx of lymphocytes and leukocytes.
Describe what occurs when you ingest an allergen?
It leads to two main symptoms:
- Activation of GI mast cells results in transepithelial fluid loss from smooth muscle contraction - vomiting and diarrhoea.
- If allergens enter bloodstream then generalised disseminated rash and urticaria.
What are the chemical mediators of an allergic response? Name an example of each
Mast cells which contain a wide range of inflammatory mediators:
- Lipids (Prostaglandins which increase vascular permeability, body temp),
- Toxic mediators (histamine which increases vascular permeability and heparin which inhibits coagulation),
- Cytokines (IL-4 which amplifys the Th2 response and TNF alpha which is pro-inflammatory),
- Enzymes
Describe the treatment of allergy?
There are two men types; desensitisation - Patients injected with escalating doses of allergen which results in a gradual shift from Th2 to Th1 cells (potential risk of anaphylaxis).
Blockade of effector pathways - Anti-histamines (H1 receptor blockers)
How should you treat severe anaphylaxis?
Injection of adrenaline. 0.15mg for child and 0.3mg for adult
Describe the theory’s of why the population are having for allergic reactions
- Hygiene hypothesis, are we not exposed to as many infectious disease in early childhood?
- Pollution, does it increase allergic asthma?
- Infection control, Allergies and asthma is lower in areas of high helminth burdens. IgE is a key defence in helminth expulsion. Data suggests helminth infections induce T cells Tregs which suppress activity of Th2 cells.
DEscribe genetic influences on allergy.
There are many genes that can influence allergy, not just one. Some examples are IL-4 promotor variants and IL-4 receptor variants
