Hypersensitivity reactions Flashcards
Define hypersensitivity
exaggerated or inappropriate immune response against a foreign of self antigen
What are the 4 types of hypersensitivity reactions?
type 1 = allergic
type 2 = cytotoxic
type 3 = immune complex
type 4 = delayed
What diseases are associated with type 1 hypersensitivity?
allergic rhinitis
asthma
atopic dermatitis
anaphylaxis
What diseases are associated with type 2 hypersensitivity?
AIHA
myasthenia gravis
Goodpasture’s disease
graft rejection
What diseases are associated with type 3 hypersensitivity?
serum sickness
Lupus nephritis
Arthus reaction
What diseases are associated with type 4 hypersensitivity?
contact dermatitis
tuberculosis
Mediators of type 1 hypersensitivity reactions
antigen/IgE cross-linking on mast cells and basophils
Th2 cells
histamine
Mediators of type 2 hypersensitivity reactions
tissue-bound IgG/IgM activates complement or effector cells
Mediators of type 3 hypersensitivity reactions
formation of antigen-IgG immune complexes
Mediators of type 4 hypersensitivity reactions
memory T cells (not by antibodies like others)
What are the key phases of type 1 hypersensitivity reaction?
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
Define asthma
immediate bronchospasm due to mast cell-released spasmogens
What are the potentially fatal consequences of anaphylaxis?
laryngeal oedema
bronchial constriction
peripheral oedema
Signs and symptoms of anaphylaxis
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
Tests for type 1 hypersensitivity
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)
Type 1 hypersensitivity treatments
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
What is the hygiene hypothesis?
limiting early life infection impeded natural immune system development and causes predisposition to allergic disease
Describe type 2 hypersensitivity reactions
directed against cell surface or extracellular matrix antigens
most common type 2 reactions involve RBCs
activation via IgG or IgM
How is an antigenic target lyses in type 2 hypersensitivity reactions?
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
What happens as ABO-incompatible donor cells enter the blood stream?
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
What causes haemolytic disease of the newborn (rhesus disease)?
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
How can drugs induce haemolytic anaemia?
drug/metabolite binds to surface protein on RBC
antibody binds to drug and activates complement
complement causes haemolysis
What causes autoimmunity?
IgG directed against self-antigens on tissues
Describe type 3 hypersensitivity reactions
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
Which conditions can cause granulomatous type 4 hypersensitivity?
TB
Leprosy
Leishmaniasis
Schistosomiasis
What is the most clinically-important form of type 4 hypersensitivity?
granulomatous type 4 hypersensitivity
- develops after 21-28 days
- antigen persistence causing chronic T cell and macrophage activation leading to granuloma formation
