What best describes a type 2 hypersensitivity?
IgG/IgM mediated. Binds to a self antigen on a cell and causes destruction of that cell.
Learning Objective 1
List the components of the Type II reaction and describe their role in a Type II hypersensitivity reaction. Highlight the antibody that most commonly mediates this reaction.
Antibody binds to a self cell or cell matrix.
The typical isotype is IgG. Can be IgM in the case of blood transfusions.
What is the major difference between type 2 and type 3 hypersensitivities?
In type 2, antibodies bind to cells or cell matrix (not a soluble antigen).
In type 3, antibodies bind to soluble antigens.
Name a few examples of type 2 hypersensitivities.
Immune-mediated hemolytic anemia
Hemolytic disease of the newborn
Blood transfusion reactions
This is a type 2 hypersensitivity reaction. What disease do you suspect?
Learning Objective 2
Describe how cellular targets are destroyed in type 2 hypersensitivities. Compare and contrast to other killing mechanisms discussed.
The same mechanisms used to kill pathoges, but antibodies are directed against self cells and matrices.
- Complement fixation and MAC formation leading to cell lysis
- Antibody dependent cell-mediated cytotoxicity (ADCC) mediated by NK cells, neutrophils, and macrophages. Release of granule contents.
- NK cells initiating apoptosis through activation of the caspase cascade.
What clinical signs would you expect in an animal that is producing IgG against its own erythrocytes?
Anemia from lack of erythrocytes
Jaundice from lysed RBCs
How does acquired myasthenia gravis cause disease?
Body produces auto-antibodies against acetylcholine receptors (AChR), which block the receptor. Act as receptor antagonists.
ACh signaling cannot occur, resulting in muscle weakness that worsens with exercise. Pelvic limbs are often most affected.
Can cause megaesophagus.
How does the Tensilon test work in testing for myasthenia gravis?
In myasthenia gravis, autoantibodies inhibit the function of acetylcholine receptors.
Tensilon is an acetycholinesterase inhibitor. ACh secreted into the synaptic cleft will hang around longer when Tensilon is administered.
The animal will temporarily lose the symptoms of muscle weakness until the Tensilon wears off.
Which complement pathway would you expect to be activated by binding of auto-antibodies in Pemphigus Foliaceous?
Which complement components are chemotactic for neutrophils and eosinophils?
What molecules do antibodies attack in the disease pemphigus foliaceous?
An inter-epidermal cell adhesion molecule
What techniques could you use to test for pemphigus foliaceous?
(might be a good idea to practice drawing these)
Describe intravascular and extravascular hemolysis
Intravascular - Occurs in the blood stream. Complement fixation and cellular lysis.
Extravascular - Occurs in the spleen and liver. Opsonization and phagocytosis.
Which auto-antibody isotype to RBCs would carry a worse prognosis: IgG or IgM?
IgM can fix complement through binding of a single antibody to its antigen. This can quickly result in intravascular hemolysis.
Describe the Coomb's test for detecting auto-immune hemolytic anemia (AIHA) in a dog.
- Take a blood sample from the dog.
- Add anti-dog IgG (Coomb's reagent) to the blood.
- If agglutination occurs, this suggests that IgG was present on the dog's RBCs.
What kinds of molecules are red blood cell antigens?
Glycoproteins and glycolipids
Learning Objective 3
Define natural antibodies.
Antibodies against foreign antigens found in an animal's serum that are present even though the animal has never been exposed to that antigen.
Why are O blood type humans considered the universal donors?
O-type RBCs do not have antigens on their cell surface. Thus, they will not react with natural antibodies present in the blood recipient.
If a human has type A blood (like Greg!), what kind of natural antibodies will be present in the serum?
Does hypersensitivity to blood transfusions require a sensitization period (like in type 1 hypersensitivities) if natural antibodies are present?
If natural antibodies are present in the serum, they will react immediately to transfused blood of a foreign antigen type. This is why it is important to blood type a blood recipient and cross-match donor blood with patient serum.
You have an exotic cat with type B blood. What would be the major concern with administering type A blood into this cat?
Type B cats have a strong hemolysin natural antibody against type A blood.
Administering A blood into a B cat will result in rapid hemolysis, shock, and death.
What is the difference between acquired antibody and natural antibody?
Natural antibody is present in an animal's serum withouth the animal ever having been exposed to that antigen. (They probably form as a result of immune system interactions with bacteria with similar antigens).
Acquired antibodies are formed after primary immune responses resulting from contact with an antigen.
Learning Objective 4
Define cross match and blood typing and explain the tests used to determine each.
Blood typing is used to determine the antigen type on the RBCs of an animal. Adding antibody against the antigen type will cause the cells to visibly agglutinate.
Cross matching insures that donor blood is compatible with recipient serum. Mix donor RBCs with patient serum. If hemolysis occurs, the two are incompatible.
Why are AB cats considered the universal blood recipients?
AB cats do not have natural antibody against either A or B blood types.
Can natural antibodies cross the placenta?
Natural antibodies are IgM isotype, which are too large to cross the placenta.
A type B mother cat has a type AB fetus in her uterus. Are you concerned for the health of this fetus?
The mother's natural antibodies against the A component of the fetus's RBCs will not cross the placenta.
The only concern might be when the baby suckles colostrum, in which case some anti-A antibody could be absorbed through the gut.
Identify the blood types of these cats.
Look for agglutination
Cat 1 - Type B
Cat 2 - Type A
Cat 3 - Type A
Cat 4 - Type A
What clinical signs are you seeing in this foal?
In this case, the symptoms are the result of hemolytic disease of the newborn. The icterus results from hemolysis and release of hemoglobin.
How might a mare become sensitized to the RBC antigens of her foal that has an opposite antigen type?
The placenta is torn during parturition. The mother is exposed to the foal's antigens at this point and will start producing antibodies.
This is not a problem for the current foal, but can be problematic with subsequent foalings.
Learning Objective 5
Explain the purpose for cross matching and blood typing and why they are important.
Cross matching insures that donor blood will be compatible with recipient serum.
- Major cross match - Will recipient serum destroy donor RBCs? Mix recipient with serum with donor cells and look for lysis.
- Minor cross match - Will donor serum harm recipient cells? Mix donor serum with recipient cells and look for lysis. Less clinically important.
Learning Objective 6
Explain why blood typing and cross matching are especially important before a blood transfusion in some exotic breeds of cats.
Type B cats have a strong hemolytic natural antibody against type A blood antigens.
Transfusing A type blood into a B type cat will cause rapid lysis of RBCs, resulting in shock and death.
Do dogs have natural antibodies against opposite blood types?
Learning Objective 7
Explain why it has been said that in the dog you can do one transfusion without a cross-match.
Dogs do not possess natural antibodies against opposite blood antigen types. So, you can transfuse a mismatched blood type into a dog without any concern for hemolysis.
After this, the dog will become sensitized to those RBC antigens. Transfusion of a mismatch a second time can be fatal.
Learning Objective 8
Explain the factors that result in hemolytic disease of the newborn.
Fetus has an antigen that the mare does not possess on the erythrocytes. If the mother has never been exposed to the antigen before, this is not a problem. She will be sensitized and will make IgG against the antigen.
In subsequent pregnancies, the antibody can cause problems when the foal suckles colostrum.
A mare is producing IgG against the erythrocyte antigens possessed by her foal in utero. SHOULD YOU START PANICKING?!?!
Keep your cool, bro.
Remember that no antibody can cross the placenta in horses. You should withhold the mother's colostrum from the foal to insure that the IgG is not absorbed systemically.
Provide the foal with a compatible colostrum instead.
Learning Objective 9
Describe the major difference between hemolytic disease of the newborn in humans and in foals
In humans, IgG against Rb antigen can cross the placenta and harm the fetus.
In the foal, IgG against erythrocyte antigens cannot cross the placenta. The problem occurs when the foal suckles colostrum and absorbs the IgG systemically. This results in hemolysis.
Learning Objective 10
Explain how Rhogam, in human medicine, prevents erythroblastosis fetalis in humans and how we prevent hemolytic disease of the newborn (HDN) in veterinary medicine.
Rh factor in humans is an erythrocyte antigen. There is no natural antibody agaisnt it, but it is strongly immunogenic. An Rh negative mother can become sensitized and produce IgG against an Rh positive fetus.
Rhogam is an antibody to the maternal IgG that prevents the fetus from being harmed.
In veterinary medicine, simply withhold colostrum from the foal and administer replacement colostrum. Once the gut closes, the foal can drink the mother's milk.
Learning Objective 11
For HDN in horses, explain what the best source for RBCs would be if a blood bank was not an option and what preparation (in general terms) would be required before giving the RBCs to the foal.
The best choice for a transfusion is the mare's RBCs. Her cells do not have the antigen that the IgG is reacting to, so will not be lysed by the absorbed antibody in the foal. The sire's cells would be a bad choice because they possess the reactive antigen.
Make sure to wash the mare's cells well to remove any serum. You don't want to infuse any more damaging antibody!