Hypersensitivity Type 2 Flashcards
What is a type 2 hypersensitivity reaction?
Direct cell killing as antibodies are bound to cell surface antigens leaving the heavy chain region exposed to interact with other cells and Fc receptors.
What is the pathophysiology of type 2 hypersensitivity reactions?
1) An antibody (IgG) produced by a self reactive B cell binds to a cell surface antigen (own cell) which results in:
a) activation of compliment: cell lysis and opsinisation
b) opsinisation: antibody mediated phagocytosis
2) IgM and IgG trigger activation of the classical pathway => complement activation
3) Opsinisation => effective phagocytosis because phagocytes express PRR and Fc receptors on their surface
What is type 2 hypersensitivity also known as?
Cytotoxic hypersensitivity
Why is type 2 hypersensitivity tissue specific?
Because the antibodies are specific to one type of tissue or organ
What is ADCC and why does if happen?
Antibody dependent cellular cytotoxicity
NK cells and eosinophils are activated
How does activation of the complement system lead to cell death?
1) C3b causes direct killing by grouping with other complement molocules to form the membrane attack complex MAC
2) Opsinisation using C3b, CRP and IgG enhances phagocytosis of macrophages and neurtophils
Give an example of type 2 hypersensitivity?
Autoimmune haemolytic anaemia s
1) Acute haemolytic transfusion reaction
2) Drug induced haemolysis
How is AHTR (acute haemolytic transfusion reaction) managed?
1) Stop transfusion and manage airway
2) Plasmapheresis- remove pathogenic antibody. Only 50% of plasma removed in one go
3) Immunosupression- rebound antibody production will limit the efficacy of plasmapheresis so given immunosupressant to switch off B cell production of antibody
What is AHTR (acute haemolytic transfusion reaction)?
ABO incompatibility. The lysis of donor erythrocytes by preformed recipient IgG.
Incompatabilit => complement mediated haemolysis of transfused RBCs
If you are blood group A, what antigens do your RBCs express and what antibodies are naturally in your serum
RBC’s express A antigen and your serum naturally contains the B antibody
What are the symptoms of AHTR?
Increased RR, HR but a decreased SaO2
Kidney problems => haemoglobin in the urine
What is drug induced haemolysis?
1) Penacillin is too small to induce antibodies but penicillin binds to a protein on RBCs
2) Protein-peniillin omplex acts as an antigen => immune response
3) Although the patient has anti-penacillin antibodies, they willnot react with normal red cells but if the patient takes penicillin again, the antibodies will react with the protein penicillin complex
4) The antibody also binds to an Fc receptor on splenic macrophages => lysis of RBCs
How is drug induced haemolysis managed?
1) Stop drug delivery and manage airway
2) Plasmapheresis- remove pathogenic antibody. Only 50% of plasma removed in one go
3) Immunosupression- rebound antibody production will limit the efficacy of plasmapheresis so given immunosupressant to switch off B cell production of antibody
What are C3a and C5a used for?
Chemotaxins to attract other immune cells
Anaphylotoxins which increase the permeability of blood vessels.
What are the 3 pathways that activate the compliment pathway?
1) Classical pathway triggered by IgM and IgG
2) Alternative pathway- spontaneous C3 cleavage
3) Manose-lectin binding pathway- no antibody but pathogen present
