11 - Allergy Flashcards
Allergy
- The inappropriate reaction of the immune system to a substance (allergen)
- One of four types of hypersensitivity reactions of the immune system
Examples of allergens
Pollen, animal dander, dust mite, food, stings
Hypersensitivity
- Refers to undesirable immune reactions produced by the normal immune system
- Requires a pre-sensitised (immune) state of the host
- Four types based on the mechanisms involved and time taken for the reaction
Type 1 hypersensitivity reaction
- Allergies
- Mediated by IgE antibodies, with mast cell activation the major final effector
- Individual had to become sensitised to the allergen by producing IgE antibodies against it
- Subsequent exposure leads to symptoms
Type 2 hypersensitivity reaction
- Antibody-mediated destruction of cells by IgG and IgM antibodies through complement activation, Antibody-dependant cellular cytotoxicity (ADCC) and Opsonisation
- e.g. Grave’s disease, Myasthenia Gravis.
Type 3 hypersensitivity reaction
- Immune complexes are formed when antibody
binds with antigen and are usually removed by
macrophages after complement activation - Persisting immune complexes can be deposited
in blood vessels and in a range of tissues and
organs; and cause inflammation – vasculitis,
glomerulonephritis, arthritis, SLE
Type 4 hypersensitivity reaction
- Delayed type
- excessive T cell activation
- Hypersensitivity reactions are mediated by T cells (primarily Th1 subtypes, but also Th17 and CD8)
- Antigens are processed and presented to T cells by APCs (sensitization). This is followed by an effector phase upon re-exposure to the antigen
Symptoms of allergic reaction
hives, swelling of lips eyes or face, vomitingm wheeze
Allergic reactions
- Development of symptoms following exposure to allergen
- Can be IgE or non IgE mediated
- Can range from mild to severe (anaphylaxis)
- Can affect multiple body systems
Anaphylaxis
- Severe reaction of rapid onset, involving multiple organ systems which results in circulatory collapse and drop in BP
- Can be fatal
Development of an allergy
- Requires pre-sensitisation to the allergen
- Once sensitised (immunised), every following exposure to the allergen elicits the allergic reaction
Immunology of an allergic response
- After a B cell comes into contact with an allergen exposed T cell it will differentiate into an antibody secreting plasma cell
- IgE antibodies produced by the plasma cell will bind to the surface of mast cells
- Upon subsequent allergen exposure, IgE antibodies on the surface of mast cells become cross-linked by the allergen
- Mast cells then degranulate –> release of vasoactive amines, lipid mediators, enzymes, cytokines, chemokines
Two phases of allergic response
- Early (minutes): Classic allergic reaction, hypotension
- Delayed (hours): late phase reaction, Eosinophil infiltration, Neutrophil infiltration, late phase reaction, Fibrin deposition
Classification of allergic reactions
- Immediate (<1hour): anaphylaxis hypotension, wheezing - IgE
- Accelerated (1-<72hours): swelling, wheezing - IgE
- Late (>72 hours): rash, cytopenias , hypersensitivity (organ involvement) - non IgE
Common allergic disorders
- Allergic rhinitis (hay fever)
- Asthma
- Food allergy
Allergic rhinitis
- Inflammation of the nasal mucosa due to hypersensitivity to environmental allergens
- Nasal irritation, rhinorrhoea, nasal obstruction are seen
- Mediated by degranulation of mast cells and eosinophils
- Effects felt within minutes of exposure to the allergen
Role of histamine, leukotrienes and prostaglandins in allergic rhinitis
- Immediate phase reaction (few minutes)
- Causes smooth muscle contraction, redness, itching, nasal discharge
Role of cytokines (IL-4, IL-13, etc), chemokines and enzymes in allergic rhinitis
- Last phase reaction (hours)
- Eosinophil –> Leukotriene and enzymes –> edema, induration, bronco-constriction
Role of cytokines, enzymes and radicals
Injury to epithelial cell –> remodelling after a few months
Asthma
- ## Many cell types play a role, in particular mast cells, eosinophils and T-lymphocytes
Airway inflammation
Early event in asthma, primarily allergen mediated, some contribution from other environmental factors (pollution, smoking)
3 components of airway inflammation
- Infiltration of cells
- Change in resident cells
- Changes in the non-cellular components of the airway wall
Cellular infiltration
- Eosinophils and CD4+ lymphocytes infiltrate the airway wall
- Th2 T lymphocytes predominate, secreting IL-4, IL-5 IL-13, etc
- IgE production
Airflow limitation
- Chronic mucus plug formation (persistent airflow limitation in severe intractable asthma)
- Airway remodelling (irreversible)
Mild - moderate symptoms of food allergy
Swelling, skin hives, abdominal pain
Factors affecting symptom severity of food allergy
- Severity of allergy
- Amount eaten
- Form of food (liquid absorbed faster)
- Asthma
- Alcohol
Diagnosis of food allergy
For IgE mediated allergy: skin test (cutaneous test) and blood test
Blood tests in food allergies
- Tryptase level can be elevated due to cell degranulation (can have false negatives)
- Elevated eosinophil count
