Type I hypersensitivity and Anaphylaxis

Question 1

define shock

Answer 1

• Shock: Failure to maintain an adequate cardiac output, or similar definition.

Question 2

name the types of shock and what can cause them

Answer 2

• Hypovolaemic: haemorrhage, or severe fluid loss eg cholera.
• Obstructive: eg the classical causes are pulmonary embolus or tamponade.
• Cardiogenic: Myocardial infarction, valvular disease, myocarditis or cardiomyopathy: heart failure.
• Distributive: septic
• Distributive: anaphylactic
• (Distributive: neurogenic shock)

Question 3

what are three types of distributive shock

Answer 3

• Distributive: septic
• Distributive: anaphylactic
• (Distributive: neurogenic shock)

Question 4

what does innate immunity also include

Answer 4

• Gross anatomical features such as intact skin, normal muco-ciliary escalator, normal emptying of bladder, normal flora

Question 5

describe the differences between innate immunity and adaptive immunity

Answer 5

Innate

• varied receptors that can recognise varied amount of substances
• the antigen receptor is directly encoded
• no memory
• no damage of autoimmunity
• neurotprhils, mast cells, macrophages, eosinophils, basophils, NK cells

adaptive

• one specificity
• each cell randomly mutates genes
• has clonal expansion
• has memory
• there is a danger of autoimmunity but this is why they have clinical deletion
• made out of B and T lymphocytes

Question 6

what is clonal deletion

Answer 6

• Deleted B or T cell if it is a component of a cell that is our own

Question 7

describe B lymphocytes

Answer 7

• Matures in the bone marrow
• Antigen receptor is antibody
• Recognise antigen anywhere
• Secretion of receptor – considerable by plasma cells (antibodies)
• Somatic mutation of the antibodies, class switching – all is initially expressed as IgM and then it changes to what is specified

Question 8

describe T lymphocytes

Answer 8

• Matures in the thymus
• Antigen receptor is not antibody
• Only recognises when presented on surface of another cell
• Has little or non-secretion of receptor

Question 9

what FC receptor is on neutrophils and monocytes in composed on a mast cell

Answer 9

• Matures in the thymus
• Antigen receptor is not antibody
• Only recognises when presented on surface of another cell
• Has little or non-secretion of receptor

Question 10

what does IgG do

Answer 10

• IgG can block pathogen binding, activate complement, & opsonise antigen for phagocytes. It is specially transported across the placenta.

Question 11

what does IgM do

Answer 11

• IgM can block pathogen binding, activate complement

Question 12

what does IgA do

Answer 12

• IgA can block pathogen binding. It is present in many secretions: tears, digestive juices etc.

Question 13

what does IgE do

Answer 13

• IgE activates mast cells. – measured in kilounits, it is all bounded on to mast cells and basophils

Question 14

what does IgD do

Answer 14

• IgD is not secreted, & function is unknown

Question 15

name the ways in which the mast cells and basophils are activated

Answer 15

• via cross linking of the surface IgE by antigen
• via complement C3a AND C5a
• via nerves - axon reflex of sensory nerves, substance P
• directly direct contact with the pathogen

Question 16

describe the ways in which mast cells and basophils are activated

Answer 16

1. Via Cross-linking of surface IgE by antigen. – bound by Fc receptors, if the IgE is cross linked by an antigen then they will activate a mast cell and basophil
2. Via Complement: C3a & C5a – these then activate mast cells and basophils
3. Via nerves: axon reflex of sensory nerves, substance P – nerves can also activate mast cells, sensory nerves set of from the skin to the spinal cord, just after they left the skin there is another little branch, this branch terminates where mast cells are and secretes substance P (a neurotransmitter) which activates mast cells
4. Directly, direct contact with pathogen, ? Innate receptors. – maybe they have innate receptors and thus activated on direct contact with the pathogen

Question 17

what is the alternative complement pathway activated by

Answer 17

inhibited by self molecules recognises and is activated when something is missing, but if a cell comes in that lacks self molecules an alternative pathway activated and continues producing C3a
- classic complement pathway doesn’t need antibodies to activate it

Question 18

name the two complement pathways

Answer 18

• classical

- alterative

Question 19

what is hypersensitivity

Answer 19

this is when the immune system damages itself, it is an immune response against outside stuff or autoimmune but either way it damages you

Question 20

describe hypersensitivity type 1

Answer 20

• Mast cell activation.

- Release of mediators: Histamine, leukotrienes (& prostaglandins).

Question 21

what does histamine do

Answer 21

increase in permeability of post-capillary venules, vasodilatation of arterioles, itch, contraction of some smooth muscle.

Question 22

what does leukotrienes do

Answer 22

Increase in permeability of post-capillary venules, chemotaxis.

Question 23

what do prostaglandins do

Answer 23

arteriolar dilatation, pain, fever.)

Question 24

what is atopy

Answer 24

• the inherited predisposition to make IgE to common environmental antigens

Question 25

what are the clinical manifestations of type I hypersensitivity

Answer 25

1) Local. Allergic rhinitis, asthma, atopic eczema (not sure what is happening here), some urticaria, some angioedema (usually accompanied by urticaria).
2) Systemic: anaphylactic shock. The patient does NOT have to be atopic to get anaphylactic shock

Question 26

what are the clinical manifestations of anaphylactic shock

Answer 26

Drop in Blood pressure because of leak of fluid into interstitial space (redistribution!) & dilation of great veins. Peripheries often warm, unlike other kinds of shock.

Urticaria (hives) raised itchy red rash (inflammation in dermis), & sore red itchy eyes. Erythema. Sudden onset of nasal soreness, secretions, sneezing.

Angioedema, (swelling in subcutaneous tissues): face, lips, hands, feet, pharynx (feeling of lump in throat) larynx (stridor, respiratory obstruction).

Bronchoconstriction (wheeze, respiratory obstruction).

Nausea & vomiting.

Abdominal bloating, diarrhoea. Metallic taste in mouth.

Headache, confusion, loss of conciousness, very rarely fit. Poor perfusion or intracranial angioedema.

Feeling of impending doom.
Cardiac arrest & Death.

Question 27

what are the antigens that trigger anaphylaxis

Answer 27

• Drugs: in a way these are the most important because they are your responsibility. Beta lactams – penicillins, carbapenems, cephalosporins, & monobactams. Significant cross-reactivity between all these. Also aspirin, NSAIDS, insulins (esp non-human), local & general anaesthetics.
• Latex.
• Foods: Peanuts. Also true nuts (walnuts etc), fish, shellfish, milk eggs, others
• Arthropod venoms: bee stings etc.
• Exercise can predispose. Some are idiopathic.

Question 28

what is the acute treatment for anaphylaxis

Answer 28

• Intramuscular adrenaline 500 micrograms in 0.5mls. Can be self-administered as Epipen 300micrograms in 0.3mls. Can give 50micrograms by slow iv infusion if circulation very impaired
• Oxygen high flow.
• Fluids iv: put up a drip. – can give adrenaline through that
• Antihistamines: chlorpheniramine 10mg im or iv
• Glucocorticosteroids: 200mg hydrocortisone

Question 29

how do you prevent anaphylaxis

Answer 29

• take careful history and ask about drug allergies - important to label them as allergic
• • Specific IgE blood tests, & skin prick tests.
• • Desensitisation
• omalizumab, a monoclonal antibody against IgE

Question 30

how does desensitisation work

Answer 30

Antigen is administered sublingually or subcutaneously, under medical supervision. Somehow this induces replacement of IgE response with IgA or IgG, or plain abolition of IgE response.

Question 31

describe the problem with omalizumab

Answer 31

omalizumab, a monoclonal antibody against IgE, is very very very expensive & licensed only for status asthmaticus, and some chronic urticaria. In theory it might work as prophylaxis for anaphylaxis, but is much too expensive & impractical: would require intravenous injections for ever.

Question 32

how is atopy inherited

Answer 32

Not certain. The signals that induce class switching are not fully understood.
Downstream of the initial signal, interleukin 4 (IL4) seems to be involved. This is secreted by CD4 Th2 T-lymphocytes, and is involved in
1.	autocrine stimulation of the T-lymphocytes.
2.	The delivery of help: paracrine activation of the B-lymphocytes that are presenting the antigen.

Somehow, in addition to this general B-lymphocyte activation signal it seems to deliver specific instructions to class switch to IgE, & there is evidence that the inherited genetic factor has to do with the switching on of IL4 secretion.