14-10-22 – Allergies Flashcards
Learning outcomes
- To describe and understand the types of molecules that act as allergens.
- To understand how the route of delivery of allergen influences the symptoms.
- To describe the cells involved in allergic responses
What is the definition of allergy?
Where do allergies reside?
- Allergy is defined as ‘disease following a response by the immune system to an otherwise innocuous antigen’
- Allergies reside within Hypersensitivities, defined as ‘harmful immune responses that produce tissue damage
For the 4 types of hypersensitivity reactions, what is the:
* Immune reactant
* Antigen
* Effector mechanism
* An example
What is allergy mediated by?
When does it occur?
How common are allergies in the West?
- Allergy is IgE mediated (Immunoglobulin E aka Antibody E)
- Allergy always occurs on secondary exposure to an allergen, so an initial exposure event has always taken place
- Allergies very common in West, often between 25 and 50% of population have allergy
When does allergy occur?
What is IgE produced by?
Why is IgE serum level low?
What can certain antigens and routes of delivery favour in terms of IgE production?
Which T-cells favour IgE responses?
What can these T cells force T cells to do?
- Allergy occurs when IgE triggers Mast cell degranulation through IgE receptor FcER1
- IgE is produced by plasma cells in lymph nodes, or locally at the site of inflammation
- Normal IgE serum level is low (0.0003mg/ml), as it is located mostly in tissue bound to Mast Cell surface through high affinity IgE receptor FcER1
- Certain antigens and routes of delivery appear to favour IgE production (Transmucosal at low doses is often a common route)
- CD4+ T cells of the Th2 phenotype that produce IL4 cytokines favour IgE responses
- Th2 T cells also force B cells to switch the isotype of the Ig they secrete from IgM to IgE
What are 4 different common sources of allergens?
What are examples of each?
- 4 different common sources of allergens:
1) Inhaled materials
* Plant pollens
* Dander of domesticated animals
* Mould spores
* Faeces of very small animals e.g house dust mites
2) Injected materials
* Insect venom
* Vaccines
* Drugs
* Therapeutic proteins
3) Ingested materials
* Food e.g nuts or shellfish
* Orally administrated drugs
4) Contacted materials
* Plant leaves e.g poison ivy
* Industrial products made from plants
* Synthetic chemicals in industrial products
* Metals e.g nickel coin
What are 6 different features of some inhaled allergens?
How do they affect the functioning of the allergen/body?
- 6 different features of some inhaled allergens:
1) Protein - only proteins induce T cell responses
2) Enzymatically active - allergens are often proteases
3) Low dose - favours IL4 producing CD4 T cells.
4) Small size - allergens can diffuse out of particle
5) Highly soluble - elutes readily from particle
* Elute - remove (an adsorbed substance) by washing with a solvent
6) Stable - allergen can survive desiccation (drying out)
What is IgE a crucial part in host defence against?
What are many allergens?
Give an example of how a major allergen gains greater access in the host.
How does the host’s immune system respond to this?
- IgE is a crucial part in host defence against parasites, many of which gain access by secreting proteolytic enzymes
- Many allergens are enzymes
- The major allergen in faeces of house dust mites is Der p 1, which can cleave tight junctions between epithelial cells in the airway, thus enhancing access
- Der p 1 can be taken up by dendritic cells of the host’s immune system and presented to CD4+ T cells of the Th2 phenotype, which force B cells to secrete IgE.
What is the most important factor in what symptoms antigens cause?
What will inhaled antigens cause?
What 2 things will this be accompanied by?
How can allergic asthma be caused?
- The location and distribution of the antigen is the most important factor in what symptoms occur
- Inhaled antigens will affect nasal epithelium, causing allergic rhinitis (hay fever) due to seasonal pollens
- This will also be accompanied by:
1) Local oedema
2) Nasal discharge, often containing eosinophils
- Allergic asthma can be cause if there is allergen induced degranulation further down airway
What is allergic asthma?
What does it lead to the increased secretion of?
What is FEV?
How does this affect FEV (forced expiratory volume)?
Why might chronic inflammation ensue?
What is chronic asthma drive by originally?
What can it result in?
- Allergic asthma is bronchial constriction in response to an allergen
- Allergic asthma also leads to acute inflammation and the increased secretion of fluid and mucus, which traps inhaled air
- Forced expiratory volume (FEV) refers to the volume of air that an individual can exhale during a forced breath in t seconds
- This acute response leads to a large decrease in FEV
- Chronic inflammation may ensue with continued presence of Th2 T cells, eosinophils, neutrophils
- Chronic asthma is driven originally by a specific allergen, but may then result in hyperreactive airways to other irritants such as cigarette smoke and other pollutants
What do allergens entering at skin sites cause?
What is the wheal and flare response?
Describe the stages of it
- Allergens entering at skin sites cause rashes
- The wheal and flare response is a descriptor used when talking about a two stage allergic response seen in Type 1 hypersensitivity.
- The first stage, called the wheal, is controlled by substances called acute phase mediators.
- The first stage (wheal) appears within a few minutes as a result of vasodilation after Mast Cell degranulation, which causes localised redness
- The second stage, called the flare, is controlled by substances called late phase mediators
- The second stage occurs around 8 hours later, with more diffuse oedema at site due to influx of lymphocytes and other leukocytes, which are attracted by chemokines.
What are the 3 potential symptoms of ingested allergens?
- 3 potential symptoms of ingested allergens:
1) Activation (degranulation) of GI Mast cells results in transepithelial fluid loss and smooth muscle contraction, leading to diarrhoea and vomiting
2) If allergen enters bloodstream, a generalised disseminated rash is caused, (Urticaria aka hives).
3) In severe cases of food allergy, eg nuts and shellfish, life threatening generalised anaphylaxis and cardiovascular collapse may occur
What 4 groups of inflammatory mediators do mast cell granules contain?
- 4 groups of inflammatory mediators mast cell granules contain:
1) Lipids
2) Toxic mediators
3) Cytokines
4) Enzymes
What 3 lipids do mast cell granules contain?
What is their mechanism of action?
- 3 lipids do mast cell granules contain:
1) Prostaglandins
* Increases vascular permeability, which increases body temperature
2) Platelet activating factor
* Increases adhesion between endothelium and neutrophils
3) Leukotrienes
* attract and activate neutrophils, which increases vascular permeability
What 2 toxic mediators do mast cell granules contain?
What is their mechanism of action?
- 2 toxic mediators mast cell granules contain:
1) Histamine
* Increases vascular permeability, and promotes movement of fluid from the vasculature by constricting vascular smooth muscle
2) Heparin
* Inhibits coagulation
