Allergies Flashcards
Define allergy.
Disease following a response by the immune system to an otherwise innocuous antigen
What is the difference between an allergy and a hypersensitivity ?
Allergies reside within Hypersensitivities, defined as ‘harmful immune responses that produce tissue damage’
Identify the four types of hypersensitivity reactions.
Type 1- IgE–mediated release of histamine and other mediators from mast cells and basophils (due to soluble antigen, i.e. in plasma or serum)
Type 2- IgG-mediated, either due to cell surface receptor antigen (in which case, results in altered signalling by antibody) or as a result of cell or matrix associated antigen (in which case results in complement activation and Fcr mediated phagocytosis)
Type 3- IgG-mediated due to soluble antigen (i.e. in plasma or serum), results in complement activation.
Type 4 (no antibody involvement)- If TH1 cells-mediated, antigen is soluble (i.e. in plasma or serum) and results in macrophage activation.
If TH2 cells-mediated, antigen is soluble and results in eosinophil activation.
If CTL-mediated, antigen is cell-associated, and results in cytotoxicity (due to cytotoxic T lymphocytes)
Give examples of each kind of hypersensitivity reaction.
Type 1: Allergy, asthma
Type 2: Drugs (cell or matrix associated antigen), Chronic urticaria (cell surface receptor antigen)
Type 3: Arthus reaction
Type 4: Contact dermatitis and Tuberculin reaction (TH1 cells-mediated), chronic asthma and allergic rhinitis (TH2 cells-mediated), contact dermatitis (CTL-mediated)
Briefly explain how Type I hypersensitivity occurs.
Initial exposure event to allergen, resulting in insignificant response. This is sensitization, at which point the IgE antibodies (produced by B-cells (stimulated by CD4+TH2 cell following T cell activation)) to the antigen bind to FcR receptors on the surface of tissue mast cells (strategically placed at mucosal surfaces) and blood basophils.
Secondary exposure to the same allergen “cross-links the bound IgE on sensitized cells, resulting in” mast cell degranulation , also basophil and eosinophil involvement.
What proportion of the population has an allergy in the West ?
25-50% of the population
Identify the main kinds of antibodies in blood. Which is the most common in blood ? What is the serum level of IgE in blood ?
IgE IgG (most common in blood) IgM IgA IgD
Serum IgE levels very low (lowest level out of all antibodies)
How is IgE produced ? Where is IgE located
in the body ? What factors favor IgE production ?
How is IgE produced ? IgE is produced by plasma B-cells in local lymph nodes or locally at site of inflammation
Where is IgE located in the body ? IgE located mostly in tissue (hence low serum concentration), bound to Mast Cell surface through high affinity IgE receptor FcRI
What factors favor IgE production ?
a) Certain antigen exposure and dose levels and routes of delivery appear to favor IgE production, e.g. transmucosal at low doses
b) CD4+T cells of the Th2 phenotype that produce IL4 cytokines favour IgE responses
c) Th2T cells also force B cells to switch the isotype of the Ig they secrete from IgM to IgE
Identify the molecules and effector action produced by different types of T cells.
CD8 cytotoxic (i.e. cytotoxic T cell): IFNγ, TNFα. Targets cell lysis.
CD4 TH1 (i.e. helper T cell): IFNγ, TNFα, GM-CSF. Targets macrophage activation (useful in chronic inflammatory response)
CD4 TH2 (i.e. helper T cell): IL4, IL5. Targets B cell activation (drives cells to release IgE)
Identify common allergens.
1) Inhaled materials
- Plant pollens
- Feces of very small animals (e.g. house dust mites)
2) Injected materials
- Insect venoms
- Vaccines
- Drugs
3) Ingested materials
- Food
- Oral drugs
4) Contacted materials
- Plant leaves
- Industrial products made from plants
What are the main features of some inhaled allergens ?
- Proteins, and only proteins induce T cell responses.
- Enzymatically active (allergens are often proteases)
- Low dose (favours IL4 producing CD4 T cells)
- Small size (allergens can diffuse out of particle)
- Highly soluble (elutes readily from particle)
- Stable (allergen can survive dessication)
Explain how enzymes can act as allergens. Give an example of an enzyme functioning as an allergen.
Many allergens are enzymes
IgE is thought to be crucial in host defense against parasites, many of which gain access by secreting proteolytic enzymes. Hence, an enzyme allergen will result in IgE response.
E.g. Major allergen in feces of house dust mite is Der p 1, which can cleave tight junctions between epithelial cells in airway, thus enhancing access. Der p 1 then taken up by Dendritic Cells, presented to T cells, which become Th2, and cause B cells to secrete IgE.
Explain the significance of route of allergen delivery.
Route of allergen delivery is crucial to symptoms (most important factor in what symptoms occur).
For instance, inhaled antigens will affect nasal epithelium, causing allergic rhinitis (i.e. hay fever) due to seasonal pollens. This will result in local edema, nasal discharge, often containing eosinophils. Then, allergen induced degranulation further down airway results in allergic asthma.
Describe the main symptoms and signs of allergic asthma.
- Bronchial constriction
- Increased secretion of fluid and mucus, trapping inhaled air
- Chronic inflammation may ensue with continued presence of Th2 T cells, eosinophils, neutrophils
- Chronic asthma driven originally by specific allergen, but may then result in hyperreactive airways to other irritants such as cigarette smoke and other pollutants
Explain the effect of allergic asthma on FEV1. Graph this.
As initial asthma type response occurs, dramatic reduction in FEV1 (due to degranulation and bronchial constriction) but this resolves quickly.
However, 5-6 hours later, secondary response occurs (due to other immune cells and edema) reducing FEV1 again.
Refer to graph on slide 17 of lecture on “Allergies”
