Type I hypersensitivity and Anaphylaxis Flashcards
1
Q
define shock
A
- Shock: Failure to maintain an adequate cardiac output, or similar definition.
2
Q
name the types of shock and what can cause them
A
- 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)
3
Q
what are three types of distributive shock
A
- Distributive: septic
- Distributive: anaphylactic
- (Distributive: neurogenic shock)
4
Q
what does innate immunity also include
A
- Gross anatomical features such as intact skin, normal muco-ciliary escalator, normal emptying of bladder, normal flora
5
Q
describe the differences between innate immunity and adaptive immunity
A
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
6
Q
what is clonal deletion
A
- Deleted B or T cell if it is a component of a cell that is our own
7
Q
describe B lymphocytes
A
- 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
8
Q
describe T lymphocytes
A
- 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
9
Q
what FC receptor is on neutrophils and monocytes in composed on a mast cell
A
- 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
10
Q
what does IgG do
A
- IgG can block pathogen binding, activate complement, & opsonise antigen for phagocytes. It is specially transported across the placenta.
11
Q
what does IgM do
A
- IgM can block pathogen binding, activate complement
12
Q
what does IgA do
A
- IgA can block pathogen binding. It is present in many secretions: tears, digestive juices etc.
13
Q
what does IgE do
A
- IgE activates mast cells. – measured in kilounits, it is all bounded on to mast cells and basophils
14
Q
what does IgD do
A
- IgD is not secreted, & function is unknown
15
Q
name the ways in which the mast cells and basophils are activated
A
- 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
16
Q
describe the ways in which mast cells and basophils are activated
A
- 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
- Via Complement: C3a & C5a – these then activate mast cells and basophils
- 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
- Directly, direct contact with pathogen, ? Innate receptors. – maybe they have innate receptors and thus activated on direct contact with the pathogen
17
Q
what is the alternative complement pathway activated by
A
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
18
Q
name the two complement pathways
A
- classical
- alterative
19
Q
what is hypersensitivity
A
this is when the immune system damages itself, it is an immune response against outside stuff or autoimmune but either way it damages you
20
Q
describe hypersensitivity type 1
A
- Mast cell activation.
- Release of mediators: Histamine, leukotrienes (& prostaglandins).
21
Q
what does histamine do
A
increase in permeability of post-capillary venules, vasodilatation of arterioles, itch, contraction of some smooth muscle.
22
Q
what does leukotrienes do
A
Increase in permeability of post-capillary venules, chemotaxis.
23
Q
what do prostaglandins do
A
arteriolar dilatation, pain, fever.)
24
Q
what is atopy
A
- the inherited predisposition to make IgE to common environmental antigens
25
what are the clinical manifestations of type I hypersensitivity
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
26
what are the clinical manifestations of anaphylactic shock
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.
27
what are the antigens that trigger anaphylaxis
- 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.
28
what is the acute treatment for anaphylaxis
- 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
29
how do you prevent anaphylaxis
- 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
30
how does desensitisation work
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.
31
describe the problem with omalizumab
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.
32
how is atopy inherited
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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.
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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.
