Allergy and the immune response Flashcards
Define: allergic response
Allergic reactions occur when an individual who has produced IgE antibody in response to an innocuous antigen, or allergen subsequently encounters the same allergen
Innocuous = non harmful antigen = dust, food allergen, medications
Why are IgE response the most beneficial?
They are particularly beneficial in developing countries, because they can provide immunity against parasitic infections
- IgE mounts a greater response compared to IgG but having both against an infection is even more beneficial
What is atopy and how many people suffer?
Atopy: genetic tendency to develop an allergic such as eczema - typically a heightened immune response to common allergens
In US and Europe almost half of the population have responses to one or more environmental allergens
What is a type 1 hypersensitivity reaction?
IgE is the immune reactant and is produced by plasma cells - binds to FcR and cross links them on the mast cells
Soluble antigen
Effector mechanism - mast cells
Examples of reaction: allergic rhinitis, asthma, systemic anaphylaxis
lifespan in the serum is increased from days to months
What is a type 2 hypersensitivity reaction?
Immune reactant: IgG
Antigen:
1) cell or matrix associated antigen
2) cell surface receptor
Effector mechanism:
1) complement , FCR+ cells (phagocytes, NK cells)
2) Antibody alters signalling
Examples:
1) drug allergies - penicillin
2) chronic urticaria (antibody against FCR1 alpha)
What is a type 3 hypersensitivity reaction?
Immune reactant: IgG
Antigen:
soluble antigen
Effector mechanism: complement phagocytosis (opsonisation)
Examples:
serum sickness, Arthus reactions
What is a type 4 hypersensitivity reaction?
Delayed type
Immune reactant: Th1
Antigen: soluble antigen
Effector mechanism: Macrophage activation
Examples: contact dermatitis, tuberculin reaction
Immune reactant: Th2
Antigen: Soluble antigen
Effector mechanism: IgE production, eosinophil activation and mastocytosis
Examples: chronic asthma, chronic allergic rhinitis
Immune reactant: CTL
Antigen: cell associated antigen
Effector mechanism: cytotoxicity
Examples: contact dermatitis
Define: atopy
predisposition to allergic disease, due to high IgE and/or eosinophil levels
What makes an allergen?
Protein- activate Th2 cells which drives IgE
Enzyme action- proteases are often allergens
Low dose- Favours IL-4/IL-13 which activates T cells to produce IgE (whereas high doses tend to induce IgG responses)
Low molecular weight- soluble in mucosa
Stable- can survive in desiccated particle
Can bind MHC - contains peptides that can activate T cells
What cells initiate an allergic response?
DCs in the much initiate an allergic response
1) stimulates naive T cells
2) IL-4 released to induce Th2 cells
3) Th2 cells release more IL-4 which stimulates B cells to release IgE. They also release IL-3, IL-4, IL-5, IL-9, IL-13 which stimulates more Th2 cells, eosinophils, basophils
What is sensitisation?
Repeated allergen exposure can cause sensitisation
What do polymorphisms in the genes, MHC II, IL-4 and Fcepsilon R1 predispose people to?
Autoimmune responses
What happens in IgE mediated reactions?
IgE binds Fcepsilon Receptor 1 on mast cells, activates eosinophils and basophils
Causes degranulation
Releases mediators - histamine
What responses occur during systemic anaphylaxis?
Oedema Increased vascular permeability Laryngeal oedema Circulatory collapse - hypotension Death
What responses occur during acute urticaria?
Local increase in blood flow and vascular permeability
Oedema
What responses occur during seasonal rhinoconjunctivitis (hay fever)?
Oedema of conjunctivitis and nasal mucosa
Sneezing
What responses occur during asthma?
Bronchial constriction
Increased production of mucus
Airway inflammation
What responses occur during food allergy?
Vomitting Diarrhoea Pruritis Urticaria Anaphylaxis
What are some of the mediators released during an allergic response?
Histamine
Cytokines - IL-1, IL-6, TNF-alpha
Leukotrienes, prostaglandins
Th2 cytokines - IL-4, 5, 13, GM-CSF
What are the effects of histamine?
Smooth muscle constriction Bronchiole constriction Intestinal constriction (cramps, diarrhoea) Vasodilation, swelling Enzyme activation to break extracellular matrix and eosinophils
What is the danger of a pre-existing IgE response to an allergen?
Can induce mast cell activation immediately
What is the role of cytokines in terms of antibody production?
Different cytokines induce /inhibit class switching to different isotopes of antibodies
Does environmental pollution increase allergies?
Huge amounts of pollution demonstrated greater lung injury in children but it didn’t demonstrate increased allergic responses
When do allergies to food allergens occur?
They can develop at any age
