Immunology Flashcards
What is an allergy?
An abnormal response to harmless foreign material (allergens) that can lead to tissue damage and death.
What is an atopy?
Tendency to develop allergies.
- Shows strong heritability
- Less in developing countries
What are some allergic diseases/ associated with allergy?
allergic rhinitis (hay fever), allergic asthma, atopic dermatitis, allergic conjunctivitis, oral allergy syndrome, angioedma, urticaria, anaphylaxis
What is anaphylaxis?
A serious allergic reaction that is rapid in onset and may cause death. It arises as an acute, generalised IgE mediated immune reaction involving specific antigen, mast cells and basophils.
- Reaction requires priming by the antigen followed by re-exposure
- To provoke anaphylaxis the allergen must be systematically absorbed - either after ingestion or parenteral injection
What is required for anaphylaxis to occur?
- Reaction requires priming by the antigen followed by re-exposure
- Allergen must be systematically absorbed either after ingestion or parenteral injection
According to the gel and coombes classification, what type of Hypersensitivity is Anaphylaxis?
Type 1:
IgE antibodies to a specific allergen trigger mast cells and basophils to release histamines and other cytokines. This causes an immediate reaction. Typical food allergy reactions, where exposure to the allergen leads to an acute reaction, range from itching, facial swelling and urticaria to anaphylaxis.
What are the classic symptoms/ presentations of Anaphylaxis?
- Widespread uticaria
- Cardiovascular collapse
- Facial and laryngeal oedema
- Airway obstruction
- Respiratory arrest
- Hypotension
- Nausea, vomiting and diorrhoeae
What are the possible trigger agents for anaphylaxis you may encounter in community and hospital settings?
Community:
• Foods – nuts, shellfish, dairy, egg, citrus fruits
• Venoms - wasps, bees, yellow-jackets, hornets
• Medicines – NSAIDs
• Latex -condoms, rubber gloves
• Semen
• Topical disenfectants
Hospital: • Antisera – tetanus diptheria • General Anaesthetic • Contrast dyes • Antibiotics – penicillin etc • NSAIDs – aspirin etc • Opiates • Perioperative medications • Topical benzocaine • Monoclonal antibodies • Hormones – insulin, progesterone
- can also be idiopathic
What is the pathophysiology of Anaphylaxis in general and Anaphylactic shock?
Anaphylaxis is an allergic reaction severe enough to cause shock. Shock = decreased tissue perfusion (hence oxygenation)
Triggering events:
• Anaphylactic and IgE immunologically mediated or
• Anaphylactoid and non-immunoglobulin mediated
Anaphylactic IgE Antibody reactions
• Following previous exposure to an antigen, IgE antibodies are released into circulation by Plasma cells under the influence of helper T cells
• Antibodies bind to glycoprotein receptors on tissue mast cells or blood-borne basophils sensitizing them
Following re-exposure to the antigen:
• Cross-linking of the Fab portions of two surface bound IgE molecules occur activates the cell and releases chemical mediators
Cellular Events
All the signs and symptoms of anaphylaxis may be produced by Histamine:
1. Antigen cross links two surface bound IgE molecules causes transmembrane coupling protein to activate Adenyl Cyclase
2. Increases cAMP activating Protein Kinases catalyse phosphorylation of certain proteins complex reactions that allow the movement of preformed granules towards the cell membrane release of granule associated mediators into the intracellular space
Primary Mediators:
- Histamine
- Chemotactic mediators: Neutrophil Chemotactic factor, eosinophil chemotactic factor
- Enzymes: Tryptase, Chymase, Beta-glucurinidase
- Proteoglycans: Heparin, Chondroitin Sulphate
- Antigen causes receptor perturbation with the simultaneous opening of surface Ca++ channels influx of Ca++ into mast cell Activation of Phospholipase A2
- Phospholipase A2 breaks down membrane phospholipids Arachidonic acid and Lysophospholipid
- Arachidonic acid oxygenated in cyclo-oxygenase pathways/ lipoxygenase pathway Prostaglandins, Thromboxanes or Leukotrienes
Mediators:
- Prostaglandin D2
- Thromboxane A2
- Leukotrienes – LTB4, LTC4, LTD4, LTE4
- PAF
- Cytokines: TNF
- Interleukins: Adenosine, Oxygen free radicals
Effects of Mediators: The signs and symptoms are derived from mediators released by the activation of mast cells and basophils
INFLAMMATORY ACTIVATORS: Histamine, PAF, Tryptase, Bradykinin
SPASMOGENS: Histamine, Prostaglandin D2, LTC4, LTD4
CHEMOTACTIC AGENTS: Neutrophil Chemotactic factor, Eosinophil chemotactic factor, LTB
What causes the signs and symptoms of anaphylaxis?
Effects of Mediators: The signs and symptoms are derived from mediators released by the activation of mast cells and basophils
INFLAMMATORY ACTIVATORS: Histamine, PAF, Tryptase, Bradykinin
SPASMOGENS: Histamine, Prostaglandin D2, LTC4, LTD4
CHEMOTACTIC AGENTS: Neutrophil Chemotactic factor, Eosinophil chemotactic factor, LTB
What is the reason for tachycardia and low BP in anaphylaxis?
- Hypotension: Vasodilation + Increased vascular permeability due to Histamine(and NO) –> causes Hypovolemia –>Low BP
- Tachycardia : Heart compensating for low BP
Circulatory failure
What is the reason for low oxygen sats in anaphylaxis?
- Histamine: severe Bronchospasm and upper airway oedema
What is the pathophysiology for reduced chest expansion and widespread expiratory wheeze on auscultation, shortness of breath in anaphylaxis?
- Histamine – bronchoconstriction (also LTC4, LTD4, LTE4)
- Prostaglandins and Thromboxanes- Prolonged airway hyperactivity
What is the pathophysiology for feeling ‘itchy’ all over in Anaphylaxis?
- Histamine – excites unmyelinated C-fibres which are pruriceptive
Why is there swelling in Anaphylaxis?
- Angioedema due to increase in vascular permeability (via increasing blood flow and endothelial barrier damage) due to Histamine (also LTC4, LTD4, LTE4
