Hypersensitivity reactions

Question 1

Define hypersensitivity

Answer 1

exaggerated or inappropriate immune response against a foreign of self antigen

Question 2

What are the 4 types of hypersensitivity reactions?

Answer 2

type 1 = allergic
type 2 = cytotoxic
type 3 = immune complex
type 4 = delayed

Question 3

What diseases are associated with type 1 hypersensitivity?

Answer 3

allergic rhinitis
asthma
atopic dermatitis
anaphylaxis

Question 4

What diseases are associated with type 2 hypersensitivity?

Answer 4

AIHA
myasthenia gravis
Goodpasture’s disease
graft rejection

Question 5

What diseases are associated with type 3 hypersensitivity?

Answer 5

serum sickness
Lupus nephritis
Arthus reaction

Question 6

What diseases are associated with type 4 hypersensitivity?

Answer 6

contact dermatitis
tuberculosis

Question 7

Mediators of type 1 hypersensitivity reactions

Answer 7

antigen/IgE cross-linking on mast cells and basophils

Th2 cells
histamine

Question 8

Mediators of type 2 hypersensitivity reactions

Answer 8

tissue-bound IgG/IgM activates complement or effector cells

Question 9

Mediators of type 3 hypersensitivity reactions

Answer 9

formation of antigen-IgG immune complexes

Question 10

Mediators of type 4 hypersensitivity reactions

Answer 10

memory T cells (not by antibodies like others)

Question 11

What are the key phases of type 1 hypersensitivity reaction?

Answer 11

sensitisation = IgE produced in response to allergen, IgE binds FcR on mast cells/basophils, occurs on first exposure (would not notice this reaction)

activation = re-exposure to allergen, allergen cross-links IgE causing immediate degranulation

causes tissue damage:
- vascular permeability
- mucus secretion
- immune cell infiltration

Question 12

Define asthma

Answer 12

immediate bronchospasm due to mast cell-released spasmogens

Question 13

What are the potentially fatal consequences of anaphylaxis?

Answer 13

laryngeal oedema
bronchial constriction
peripheral oedema

Question 14

Signs and symptoms of anaphylaxis

Answer 14

swelling of conjunctiva
runny nose
swelling of lips, tongue and/or throat
fast/slow HR
low BP
gives, itchiness, flushing
pelvic pain
loss of bladder control
crampy abdominal pain
diarrhoea, vomiting
SOB
wheeze/stridor
hoarseness
cough
lightheadedness
loss of consciousness
confusion
headache
anxiety

Question 15

Tests for type 1 hypersensitivity

Answer 15

skin prick test
blood test (serum IgE levels)
test diet or food challenge (patient placed on diet free from most allergens, foods added over time)

Question 16

Type 1 hypersensitivity treatments

Answer 16

allergen avoidance
desensitisation (repeated injection of small but increasing doses of purified allergen over several months –> modification of Th2 response to increase IgG)
Drugs:
- antihistamines
- corticosteroids
- leukotriene receptor antagonists
- sodium cromoglicate (blocks Ca influx into mast cells)
- salbutamol
- monoclonal IgE (Omalizumab)
- adrenaline

Question 17

What is the hygiene hypothesis?

Answer 17

limiting early life infection impeded natural immune system development and causes predisposition to allergic disease

Question 18

Describe type 2 hypersensitivity reactions

Answer 18

directed against cell surface or extracellular matrix antigens
most common type 2 reactions involve RBCs
activation via IgG or IgM

Question 19

How is an antigenic target lyses in type 2 hypersensitivity reactions?

Answer 19

ADCC (antibody dependent cellular cytotoxicity)
- Ig binding via FcR of NK cells, neutrophils or macrophages (effector cells)
- release of cytotoxic enzymes

Direct complement lysis
- classical pathway

Question 20

What happens as ABO-incompatible donor cells enter the blood stream?

Answer 20

they are lysed
intravascular haemolysis via complement-mediated lysis
leads to renal failure and death
prevent by cross-matching patient serum with donor RBC
blood typing by haemagglutination

Question 21

What causes haemolytic disease of the newborn (rhesus disease)?

Answer 21

rhesus antigens expressed on RBC surface
problems occur in pregnancy after sensitisation (not first baby)

RhD +ve fetus in RhD -ve mother
postpartum sensitisation = anti-RhD antibodies produced
subsequent pregnancy = haemolysis, anti-RhD antibodies attack RhD antigens of fetus causing lysis of RBCs

Question 22

How can drugs induce haemolytic anaemia?

Answer 22

drug/metabolite binds to surface protein on RBC
antibody binds to drug and activates complement
complement causes haemolysis

Question 23

What causes autoimmunity?

Answer 23

IgG directed against self-antigens on tissues

Question 24

Describe type 3 hypersensitivity reactions

Answer 24

similar to type 2 but antibodies directed against soluble antigens leading to formation of immune complexes

damage caused by deposition and build up of complexes in tissues or walls of small blood vessels

Question 25

Which conditions can cause granulomatous type 4 hypersensitivity?

Answer 25

TB
Leprosy
Leishmaniasis
Schistosomiasis

Question 26

What is the most clinically-important form of type 4 hypersensitivity?

Answer 26

granulomatous type 4 hypersensitivity
- develops after 21-28 days
- antigen persistence causing chronic T cell and macrophage activation leading to granuloma formation