infection - Allergies

Question 1

what is hypersensitivity?

Answer 1

the antigen-specific immune responses that are either inappropriate or excessive and result in harm to host

Question 2

what are the mechanisms underlying the inappropriate / excessive immune responses?

Answer 2

the mechanisms employed by the host to fight infections

Question 3

what are the phases of hypersensitivity reactions?

Answer 3

sensitisation phase - 1st encounter with antigen

effector phase - re-exposure to same antigen

Question 4

what are the types of hypersensitivity reactions?

Answer 4

type 1 - immediate <30mins - allergies (environmental non-infectious)
type 2: antibody mediated (5-12 hours)
type 3: immune complexes mediated (3-8 hours)
type 4: cell-mediated (24-48 hours) - environmental infectious agents & self antigens

Question 5

which gene means people get allergies?

Answer 5

TH2 phenotype

IgE production

Question 6

which gene means people don’t get allergies?

Answer 6

TH1 phenotype

Question 7

what are the environmental factors which means people are less likely to get allergies?

Answer 7

developing countries
large family size
rural homes, livestock
low Abx use
poor sanitation
intestinal microflora variability
high oralfaecal & helminth burden

Question 8

what are the environmental factors which pre-disposes people to allergies?

Answer 8

westinised countries
small familu size
affluent urban homes
high Abx use
good sanitation

Question 9

what are common allergens?

Answer 9

house dust mite (faeces)
animals (hair)
tree & grass pollen
inset venom - bee stings
medicines - Abx penicillin
chemicals - latex
foods e.g. milk, peanuts, seafood

Question 10

what is clinical cross-reactivity?

Answer 10

if you are allergic to one thing, you have an increased risk of being allergic to another e.g. cow’s milk predisposes to goat’s milk

Question 11

what are some toxic mast cell mediators? function?

Answer 11

histamine & heparin - increase vascular permeability & cause SM contraction

Question 12

what are some mast cell cytokines mediators?

Answer 12

1. TNF-alpha: promotes inflammation, stimulates cytokine production
2. IL-3, IL-5: promote eosinophil production & activation
3. IL-4, IL-13: stimulate & amplify TH2 cell response (extracellular microbes) - eosinophils, B cell, mast cells

Question 13

what are some lipid mediators of mast cell?

Answer 13

1. leukotrienes C4 (released by eosinophils?) - SM contraction, increase vascular permeability, stimulate mucus secretion
   (toxic to epithelium - shedding, asthma)
2. platelet- activating factor

Question 14

what is the immune mechanism of allergic reaction on 2nd exposure?

Answer 14

allergen bind to mast cell, causing degranulation of histamine & chemokines
and synthesis of new mediators: leukotrienes, prostaglandins
(allergen cross-linking on 2nd exposure)

Question 15

what does mast cell degranulation of histamine, chemokines, prostaglandins & leukotrienes lead to?

Answer 15

increased vascular permeability
vasodilation
bronchial constriction (SM)

Question 16

what is the difference between 1st & 2nd exposure (mechanism)?

Answer 16

1st: IgE-mediated triggering of mast cell, plasma B cell finds the antigen-specific IgE which activates the mast cell
2. irritant directly activates mast cell

Question 17

how does mast cells in EPIDERMIS activated manifest itself?

Answer 17

urticaria

Question 18

how does mast cells in face activated manifest itself?

Answer 18

angioedema
mast cells in DEEP dermis
lips, eyes, tongue, upper resp airways

Question 19

what is the systemic manifestations of allergic reaction?

Answer 19

anaphylaxis: systemic activation of mast cells
hypotension
CVS collapse
generalised urticaria
angioedema

breathing problems (broncho SM constriction)

Question 20

what are signs & symptoms of anaphylaxis?

Answer 20

1. CNS: lightheadedness, confusion, loss of consciousness, headache
2. resp: SoB, wheeze (high pitch expiratory), stridor (harsh sound during inspiration), cough
3. swelling of conjunctiva, lips, tongue (throat)
4. skin: hives, itchiness, flushing
5. CVS: tachy/bradycardia, LOW BP
6. GI: D&V

Question 21

what are the 3 rules of anaphylaxis?

Answer 21

1. sudden onset, rapid progression
2. involves at least 2 organs (one is skin / mucosa)
3. 70% CVS involvement, drop in BP enough to make diagnosis

Question 22

what is the treatment of anaphylactic shock? what is it’s MoA?

Answer 22

IM adrenaline:

1. reversis peripheral vasodilation, reduces oedema & alleviates HYPOtension
2. reverses airway obstruction / bronchospasm
3. increases force of myocardial contraction
4. inhibits mast cell degranulation (via ß2-receptor)

Question 23

what are the things you need to monitor for a patient with anaphylactic shock?

Answer 23

pulse, BP, ECG, oximetry

DO NOT DELAY TREATMENT

Question 24

how do you diagnose allergy?

Answer 24

1. history: allergens, seasonal
2. blood tests: serum allergen-specific IgE, serum mast cell tryptase, histamine
3. skin prick test: wheal & flare reaction (>3mm) - mast cell in epidermis
4. challenge tests: food & drug allergy (risk of anaphylaxis - trained personnel)

Question 25

management of allergy?

Answer 25

1. allergen avoidance / elimination
2. education - recognise symptoms & EPIPEN use
3. medic alert identification e.g. wrist-band
4. drugs: anti-histamines, corticosteroids, IM adrenaline
5. allergen desensitisation: specialist hospital based-unit with resus equipmen

Question 26

what is allergen desensitisation / immunotherapy?

Answer 26

involves the administration of increasing doses of allergen extracts over a period of years
given to patients by injection / sublingual

(effective in bee / wasp venom stings)

Question 27

what are the potential mechanisms of desensitisation?

Answer 27

shifts TH2 to TH1
inhibitory anti-inflammatory cytokines
allergen specific blocking IgG
CD4+CD25 regulatory T cells