Hypersensitivity reactions: from basics to clinic Flashcards
What does the term hypersensitivity describe?
- The antigen-specific immune responses that are either inappropriate or excessive and result in harm to hist
What are the mechanisms underlying hypersensitivity reactions?
- The same as the mechanisms employed by the host to fight infections
What are some triggers of hypersensitivity reactions?
- Exogenous antigens
- Intrinsic antigens
Give some examples of exogenous antigens that trigger hypersensitivity
- Non-infectious substances (innocuous)
- Infectious microbes
- Drugs (penicillin)
Give some examples of intrinsic antigens that trigger hypersensitivity
- Infectious microbes ((mimicry)
- Self0antigens (auto-immunity)
What are the different types of hypersensitivity reaction?
- Type I or immediate (Allergy)
- Type II or antiBody mediated
- Type III or immune Complex mediated
- Type IV or cell mediated (Delayed)
What are the different phases of a hypersensitivity reaction?
- Sensitization phase
- Effector phase
Outline the sensitization phase
- First encounter with the antigen
- Activation of antigen presenting cells and memory effector cells
- A previously exposed individual to the antigen is said to be sensitized
Outline the effector phase
- Pathologic reaction upon re-exposure
- To same antigen and activation of the memory cells of the adaptive immunity
Outline a type II hypersensitivity reaction
- Usually develops within 5-12 hours
- Involves IgG or IgM antibodies
- Targets cell bound antigens
- Induces different outcomes such as tissue/cell damage and physiological change
What are the cell bound antigens targeted by type II hypersensitivity reactions?
- Exogenous: blood group antigens, rhesus D antigens
- Endogenous: self antigens
What are the immune mechanisms of type II hypersensitivity reactions associated with tissue/cell damage?
- Complement activation - cell lysis, neutrophil recruitment (C3a/C5a), opsonisation (C3b)
- Antibody-dependent cell cytotoxicity (NK cells)
Give some clinical examples of complement activation in type II hypersensitivity reactions
- Haemolytic disease of the newborn
- Transfusion reactions
Give some clinical examples of antibody-dependent cell cytotoxicity in type II hypersensitivity reactions
- Autoimmune haemolytic anaemia
- Immune thrombocytopenic purpura
- Goodpasture’s syndrome
What causes haemolytic transfusion reactions?
- Errors in patient identification
- Improper labelling of blood specimen
- Testing errors
What is the immune mechanism behind haemolytic transfusion reaction?
- Incompatibility in the ABO antigens on RBCs
- Donor RBC lysis induced by type II hypersensitivity
- Involves recipient’s IgM
What is the clinical outcome of haemolytic transfusion reaction?
- Shock
- Respiratory distress
- Kidney failure
- Death
Outline the immune mechanism behind haemolytic disease of the newborn
- Father is rhesus +
- Mother is rhesus -
- Baby is rhesus +
- Rh antigens from developing foetus enter mother’s blood during delivery
- Mother is sensitized and produces anti-Rh antibodies
- If woman becomes pregnant with another Rh+ foetus, her anti-Rh antibodies cross the placenta
- Foetal RBCs are damaged
What are the symptoms of haemolytic disease of the newborn?
- Severe life-threatening condition
- Hydrops fetalis (drop in albumin - fluid in tissues not in blood)
- Hepato/splenomegaly
- Severe hyperbilirubinemia
- Kernicterus
Outline the immune mechanisms behind type II hypersensitivity reactions associated with physiological changes
- Receptor stimulation
- Receptor blockade
- Protein blockade
Give some clinical examples of type II hypersensitivity reactions associated with physiological changes
- Grave’s disease - increased thyroid activity
- Myasthenia gravis - impaired neuromuscular signalling
- Pernicious anaemia
What are the therapeutic approaches of type II hypersensitivity reactions that cause tissue/cell damage?
- Corticosteroids - anti-inflammatory
- Plasmapheresis - circulating antibodies and inflammatory mediators
- Splenectomy - opsonisation/phagocytosis
- Intravenous immunoglobulin - blockage of Fc receptor
What are the therapeutic approaches of type II hypersensitivity reactions that cause physiological change?
- Correct metabolism e.g. anti-thyroid drugs/ thyroidectomy in Grave’s disease
- Replacement therapy e.g. vit B12 in pernicious anaemia
Which diseases can be treated by plasmapheresis?
- Myasthenia gravis
- Goodpasture’s syndrome
- Grave’s disease
- Short term relief and allows healing of damaged tissue
