Immunology - Anaphylaxis

Question 1

Anaphylaxis

Answer 1

an acute type I hypersensitivity reaction that can be systemic and is sometimes so overwhelming that it is life -threatening, results from a response to an allergen that is present throughout the body

Question 2

Substances that can cause anaphylaxis

Answer 2

Those that can pass freely around the body (penicillin (especially if given previously intravenously), certain other drugs (ie local anaesthetics, X-ray contrast agents), venom in bee/wasp stings, peanuts (Allergen can be absorbed fast enough to cause systemic effects))

Question 3

What type of cell causes symptoms?

Answer 3

Mast cell, released as a progenitor from bone marrow, homes to connective and mucosal tissue where it matures, noted for its many granules

Question 4

What is the signalling molecule involved?

Answer 4

Histamine

Question 5

Mast cells

Answer 5

widely distributed throughout the body both in connective tissue (ie under skin) and in association with epithelial mucosae (ie respiratory and intestinal epithelia), contain prominent granules which contain a number of mediators of inflammation (notably histamine and leukotrienes) which act principally on blood vessels and smooth muscle which express specific histamine receptors (GPCRs, G-protein-coupled receptors)

Question 6

Inflammatory mediators

Answer 6

Released by mast cells, act principally on blood vessels and smooth muscle

Question 7

histamine in connective tissue

Answer 7

causes vasodilation with increased blood flow to the surface and increased movement of fluid out of the blood stream (oedema)

Question 8

histamine in mucosae

Answer 8

opposite to connective tissue, airway constriction and contraction of smooth muscle in the walls of the interstines

Question 9

Acute allergic reaction

Answer 9

Allergen specific IgE is pre-bound to the FcεR1 receptor on mast cells, circulatinf allergen binds the IgE causing receptor cross-linking and mast cell degranulation (histamines, lipid mediators, cytokines), ie wheezing + urticaria + sneezing/rhinorrhea + conjunctivitis

Question 10

Chronic allergic reaction

Answer 10

Recruitment and activation of allergen specific T cells and other cells by mast cell derived mediators, ie further wheezing + sustained blockage of the nose + eczema

Question 11

Net effect of histamines depends on

Answer 11

Whether stimulation is local or systemic

Question 12

Immunoglobulin E

Answer 12

Histamine and leukotrienes are secreted following antigen binding to the cell surface IgE, IgE response thought to be important in defence against certain parasitic infections (ie nematodes) but inappropriately = allergic reactions, binds with high affinity to Fc receptors of mast cells, present at extremely low levels in blood, cross linking by antigen triggers mast cell activation and histamine release

Question 13

Normal pathway of lymphocyte activation

Answer 13

occurs where antigen binds to the surface IgM on lymphocytes to stimulate proliferation and antibody secretion, usually the antibody initially secreted is IgM and switches to IgG as immune response progresses

Question 14

Lymphocyte activation in type I hypersensitivity

Answer 14

After normal pathway, CD4+ T helper cells (TH2) causes a switch to IgE production

Question 15

Immunoglobulin involved in anaphylaxis?

Answer 15

IgE

Question 16

What causes rashes and puffy skin?

Answer 16

If the patient has a skin allergy stimulation of connective tissue mast cells causes vasodilation leading to the red color of the skin rash and oedema leading to its raised appearance (this type of rash = urticaria (raised by lump or wheal), familiar as the pattern of rash caused by stinging nettles), localised skin reaction used in allergy testing (small amounts of possible allergens are injected by pin-prick to see if they cause wheal-and-flare reaction), can be caused by animal hair+ proteins in natural latex+certain chemicals+ substances in insect and plant stings

Question 17

Hay fever

Answer 17

If allergen is inhaled principal site of action will be mucosal mast cells of the respiratory system, if this is principally in the nasal passages the effect will be oedema in the epithelia lining the nose and a consequent general irritation including stimulation of mucus secretion (allergic reaction which causes hay fever, allergic rhinitis), caused by pollens + feces of dust mites + proteins of animal hairs

Question 18

Asthma

Answer 18

If allergen is inhaled principal site of action will be mucosal mast cells of the respiratory system, if allergen reaches bronchioles there will be contraction of smooth muscle reducing the diameter of the airways as well as inflammation and increased mucus production (difficulty breathing in and especially breathing out), caused by pollens + feces of dust mites + proteins of animal hairs

Question 19

Food allergies

Answer 19

If the allergen is ingested then it will act at mucosal mast cells in the intestinal tract, the stimulation of the associated smooth muscle leads to the vomiting and diarrhea typical of a food allergy, if the allergic substance can be absorbed and pass into the bloodstream it may also cause skin symptoms (rashes or itching), substances: peanuts+other nuts and legumes (ie soya)+ shellfish+milk+eggs+wheat

Question 20

Why should adrenaline have been given?

Answer 20

Anaphylaxis results from a systemic response to the allergen causing immediate responses throughout the body, though not common it is potentially fatal and must be treated as a medical emergency, dilatation of peripheral blood vessels causes symptoms of rashes and edema, results in a dramatic drop in blood pressure which can affect organ function (shock, constriction of bronchi causes breathing difficulty in breathing, the patient will respond with an increase in both respiratory and heart rates, there may also be symptoms of nausea+abdominal cramps+diarrhea from effects on the intestines), emergency treatment is aimed initially at hypotension and then at the underlying inflammation, the patient is lain down with feet raised in order to improve blood supply to the head and trunk, an injection of adrenaline will act to constrict peripheral blood vessels and redirect blood to the organs

Question 21

What sort of drugs might have been in the injections after adrenaline?

Answer 21

Antihistamines (ie diphenhydramine and anti-inflammatory corticosteroids ie hydrocortisone), if breathing problems persist oxygen may be necessary and bronchodilators may be given via an inhaler (ie salbutamol), long term treatment is largely by avoiding known allergens, for those difficult to avoid completely (ie wasp stings or nuts where small traces may contaminate apparently innocent foods) the patient may be given adrenaline in a self-injection pen (ie epipen, emerade)

Question 22

Why do patients feel faint?

Answer 22

Due to hypotension, syncope is a temporary loss of consciousness usually related to insufficient blood flow to brain

Question 23

Why was blood pressure monitored in hospital?

Answer 23

Reliable indication of recovery, occasionally symptoms return (usually within hours of initial reaction, biphasic anaphylaxis), patients with moderate respiratory or cardiovascular compromise should be observed fro up to 8-10 hrs before discharge