12.2 Allergy and anaphylaxis Flashcards
(33 cards)
Define allergy.
Immune responses that are potentially harmful to the host but which are directed against external agents which are themselves not
harmful.
Symptoms and diseases not caused by the allergens themselves, but by the immunological reactions to them.
Define anaphylaxis.
A severe, life-threatening generalised hypersensitivity reaction.
What is a type 1 hypersensitivity reaction?
- IgE mediated
- Allergy
- Atopy, anaphylaxis asthma
Every1 has an allergy
What is a type 2 hypersensitivity reaction?
- IgM, IgG, complement
- Cytotoxic, antibody dependent
- Autoimmmune hemolytic anemia
What is a type 3 hypersensitivity reaction?
- IgG, complement
- Immune complex disease
- Serum sickness, SLE
What is a type 4 hypersensitivity reaction?
- Lymphocytes
- Cell mediated
- Delayed hypersensitivity, contact dermatitis, hypersensitivity in TB, chronic transplant rejection
What are the effector cells in IgE mediated reactions?
- IgE = type 1
- Mast cells and basophils
- Produce 3 important classes of mediators
What mediators are produced by mast cells and basophils?
- Vasoactive amines: histamine
- Lipid mediators: prostaglandins, leukotrienes, PAF
- Cytokines: TNF, IL-4, IL-5
How does IgE bind to mast cells?
Via. IgE Fc receptors (high affinity) on the mast cell surface
Where are mast cells predominantly found?
- In the skin, respiratory and gut mucosa
- Activation of mat cells via IgE binding = degranulation (histamine release)
Name the 5 things released by mast cells.
CLECT
- Cytokines: IL-4/3/5, TNF-alpha
- Lipid mediators: leukotrienes and PAF
- Enzymes: chymase and tryptase
- Chemokines:CCL3
- Toxic mediators: histamine and heparin
Where are histamine receptors found?
Histamine released from mast cells can bind to:
- H1 receptor
- H2 receptor
- H3 receptor
- H4 receptor
What is the role of the vasoactive amines (histamine) and lipid mediators (prostaglandins and leukotrienes) released by mast cells?
- Cause the rapid vascular and smooth muscle reactions seen in immediate hypersensitivity
- E.g. vasodilation, vascular leakage, oedema, bronchoconstriction, gut hypermotility
What is the role of the cytokines released by mast cells and Th2 cells in the late phase/delayed hypersensitivity reaction (4)?
Cytokines released by mast cells and Th2 cells mediate the late-phase reaction, which is an inflammatory reaction involving neutrophil and
eosinophil infiltration.
What is atopy?
The genetic predisposition to producing IgE following exposure to common environmental allergerns.
5-10% of the population show clinical features of 1 or more allergic disorders e.g. Asthma, hay fever.
What is the atopic triad?
Describe atopy at a cellular level.
- Atopy appears to be due to a predisposition toward a T-helper type 2 response
- Th2 cells secrete large quantities of IL-) and IL-13, which promote the production of allergen-specific IgE by plasma cells
Describe the features of the allergens that promote an IgE response.
- Proteins, often proteases
- Low doses
- Low molecular weight
- Stable
- Highly soluble
- Peptides which bind to MHC II
- Mucosal presentation (usual site of parasite entry)
What is sensitisation?
- Sensitization refers to the production of allergen-specific IgE.
- Sensitization to an allergen is not synonymous with being allergic to that allergen, because individuals may produce IgE to allergens in a
given substance, but not develop symptoms upon exposure to that substance.
It is unclear why some individuals demonstrate only sensitization while others have active allergic disease.
Does sensitisation always lead to allergy?
No. Sensitisation won’t always lead to allergy. But people who have allergies would have had sensitisation initially.
Describe type 2 hypersensitivity reactions.
Antibody mediated. Cytotoxic.
IgG and IgM antibodies specific for cell surface or ECM antigens cause tissue injury (often organ specific) by:
- Activating the complement system
- Recruiting inflammatory cells
- And interfering with normal cellular function e.g. antibody mediated stimulation of the thyroid stimulating hormone receptor => Grave’s disease (hyperthyroidism)
Describe type 3 hypersensitivity reactions.
Immune complex mediated.
- Immune complexes form (Ag-Ab)
- These immune complexes may deposit in the BV walls in various tissues, causing inflammation, thrombosis and tissue injury
- E.g. lupus, rheumatoid arthritis
Describe type 4 hypersensitivty reaction.
T-cell mediated
Delayed type reaction
- Tissue injury due to T lymphocytes that induce inflammation or directly kill target cells
- T-helper cells secrete cytokines that promote inflammation and acitvate leukocytes, mainly neutrophils and macrophages
- Cytotoxic T cells also contribute to tissue injury in some diseases
- Reaction 24 to 48 hours after antigen challenge in a previously sensitised individual
- E.g. contact dermatitis
How can allergies be treated?
- Avoidance
- Drugs: antihistamines, inhalers, topical steroids, adrenaline (emergency)
- Desensitisation: currently only available for aeroallergens and venoms
