Hypersensitivity 2 and 3 Flashcards
Define Type II hypersensitivity.
• In Type II hypersensitivity, IgG or IgM antibodies bind to antigenic determinants on the surface of host cells, leading to host cell destruction by activated complement and/or by cytolytic effector cells
What are the cytolytic effector cells in Type II hypersensitivity?
• NK cells, neutrophils, eosinophils, monocytes, and macrophages.
What is the mechanism for activating the cytolytic effector cells in Type II hypersensitivity?
• Engagement of IgG Fc receptors and/or receptors for activated complement components (C3a, C3b, C5a) can lead to phagocytosis and/or release by the effector cell of
o superoxide anion (O2-)
o hydrogen peroxide (H2O2)
o tumor necrosis factor (TNF)
o or perforins (membrane perforating proteins similar to C9) that lyse the target cell.
What are four examples of Type II hypersensitivity?
- Transfusion Reactions
- Hemolytic Disease of Newborn (HDN) aka erythroblastosis fetalis
- Autoimmune Blood Dyscrasias
- Hyperacute Graft Rejection
What are Isohemagglutinins?
• Antibodies against isohaemagglutinins (wtf?) these are just the A or B proteins on blood vessels. They are called isoantigens because the are antigens from the same species of animal (as opposed to alloantigens from other species)
Explain ABO blood and how antibodies form.
- However, newborns don’t have A B antigens.
- It is still only a theory as to how we get the antigens.
- The theory taught in this class is that we gain exposure to A-like and B-like antigens from bacteria and virus in our GI tract.
- We produce antibodies to them. If we have A blood, we will eliminate the antibodies against A cells, but keep antibodies against B blood.
- From there on, we are sensitive to a foreign blood type. (and vice versa if we have B blood).
- This sensitivity occurs at 3-6 months of age, peaks at 5-10 years, and declines after that.
What happens if a person is infused with a mismatched blood type?
• If ABO mismatched red cells are infused, the serum antibodies will
o immediately agglutinate the red cells (possibly leading to life-threatening ischemia or embolism)
o or cause their destruction by complement mediated lysis
o or by phagocytosis by macrophages in the liver and spleen.
There are more than 30 blood group systems that together comprise more than 200 allogeneic antigenic variants. What happens when we receive a mismatch from other blood group systems?
- Non-ABO blood groups are mainly a problem when people have repeated transfusions.
- Sensitization results from the first encounter with the foreign antigen.
- A hemolytic reaction then occurs when erythrocytes bearing the same foreign antigen are subsequently administered.
Explain Hemolytic Disease of the Newborn aka erythroblastosis fetalis.
- Hemolytic Disease of the Newborn (HDN): HDN or erythroblastosis fetalis is an example of active immunization by exposure to mismatched red blood cells.
- In this case, a mother who is RH(-) (i.e., lacks the RhD antigen) is stimulated to make anti-D antibodies when Rh(+) red cells from the fetus enter her blood stream.
- This happens during pregnancy, and especially at parturition.
- The anti-D antibodies cause the mother no problem since her red cells are Rh-D negative.
- However, in a subsequent pregnancy with an RhD(+) fetus, maternal IgG anti-D antibodies can cross the placenta and destroy the red cells of the fetus leading to serious illness and even death of the newborn.
Thought Question: Explain why HDN is less common when mother and fetus are mismatched for ABO as well as Rh antigens.
- It seems paradoxical that greater antigenic mismatch should lead to a less serious immunological response.
- However, when there is an ABO mismatch, the fetal red cells are rapidly destroyed by naturally occurring ABO antibodies.
- This eliminates the source of D antigen which must be present persistently to induce active immunity and production of anti-D antibody.
- This is the principle for Rhesus prophylaxis, in which anti-RhD antibodies are injected perinatally into Rh(-) mothers who have an Rh(+) fetus.
Explain Autoimmune Blood Dyscrasias.
• Dyscrasias is “an abnormal or disordered state of the body or of a bodily part. Stemming from the Greek root meaning bad mixture.”
• Under abnormal circumstances, autoantibodies may be produced that recognize one’s own red cells, platelets, lymphocytes or neutrophils.
• These antibody-tagged cells can then be eliminated through mechanisms of Type II hypersensitivity, leading respectively to
o Anemia
o Thrombocytopenia
o Lymphocytopenia
o Neutropenia.
Explain how Type II reactions can arise through the production of antibodies to drugs or drug metabolite (e.g. penicillin) that can associate with host cell membrane proteins and in doing so becomes a hapten.
- Drugs such as penicillin can attach to erythrocytes and cause IgG-mediated damage to erythrocytes.
- The complement and Fc receptor-dependent clearance systems then eliminate any host cell to which the particular drug or metabolite has bound.
What is the Coombs’ test? How does it test for Type II hemolytic diseases?
- Basically, in some blood diseases we produce antibodies to our own blood.
- To test for this we do a Coombs’ Test.
- We take a blood sample and “wash it.” Only the blood cells and the antibodies attached to the blood cells are left.
- We test the blood with anti-human antibodies (like from a goat). If there are antibodies attached to the blood cells, the Coombs test is positive, and the sample coagulates.
What is the treatment for patients with autoimmune hemolytic anemia, thrombocytopenia, or similar diseases?
• In patients with these disorders, a splenectomy may be performed to eliminate a major source of macrophages responsible for removing autoantibody-opsonized platelets or red blood cells.
Explain Hyperacute Graft Rejection
- Hyperacute rejection occurs when a transplant recipient has been previously sensitized to antigenic determinants found in the engrafted tissue.
- Preformed antibodies are thus present at the time of transplant, and cause Complement and/or Fc receptor-dependent destruction of the transplanted tissue.
- The most serious reactions were previously due to ABO group antigens (which are expressed on kidney cells as well as erythrocytes), but ABO cross-matching has virtually eliminated this problem (making sure the donor ABO matches the recipient ABO).
