Lecture 22 - Type 2 hypersensitivity

Question 1

What best describes a type 2 hypersensitivity?

Answer 1

Cytotoxic type

IgG/IgM mediated. Binds to a self antigen on a cell and causes destruction of that cell.

Question 2

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.

Answer 2

Antibody binds to a self cell or cell matrix.

The typical isotype is IgG. Can be IgM in the case of blood transfusions.

Question 3

What is the major difference between type 2 and type 3 hypersensitivities?

Answer 3

In type 2, antibodies bind to cells or cell matrix (not a soluble antigen).

In type 3, antibodies bind to soluble antigens.

Question 4

Name a few examples of type 2 hypersensitivities.

Answer 4

Pemphigus foliaceous

Immune-mediated hemolytic anemia

Hemolytic disease of the newborn

Blood transfusion reactions

Myasthenia gravis

Question 5

This is a type 2 hypersensitivity reaction. What disease do you suspect?

Answer 5

Pemphigus foliaceous

Question 6

Learning Objective 2

Describe how cellular targets are destroyed in type 2 hypersensitivities. Compare and contrast to other killing mechanisms discussed.

Answer 6

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
• Phagocytosis
• 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.

Question 7

What clinical signs would you expect in an animal that is producing IgG against its own erythrocytes?

Answer 7

Anemia from lack of erythrocytes

Jaundice from lysed RBCs

Question 8

How does acquired myasthenia gravis cause disease?

Answer 8

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.

Question 9

How does the Tensilon test work in testing for myasthenia gravis?

Answer 9

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.

Question 10

Which complement pathway would you expect to be activated by binding of auto-antibodies in Pemphigus Foliaceous?

Answer 10

Classical pathway

Question 11

Which complement components are chemotactic for neutrophils and eosinophils?

Answer 11

C3a

C5a

Question 12

What molecules do antibodies attack in the disease pemphigus foliaceous?

Answer 12

An inter-epidermal cell adhesion molecule

(probably desmoglein)

Question 13

What techniques could you use to test for pemphigus foliaceous?

Answer 13

Immunofluorescence

Immunohistochemistry

(might be a good idea to practice drawing these)

Question 14

Describe intravascular and extravascular hemolysis

Answer 14

Intravascular - Occurs in the blood stream. Complement fixation and cellular lysis.

Extravascular - Occurs in the spleen and liver. Opsonization and phagocytosis.

Question 15

Which auto-antibody isotype to RBCs would carry a worse prognosis: IgG or IgM?

Answer 15

IgM

IgM can fix complement through binding of a single antibody to its antigen. This can quickly result in intravascular hemolysis.

Question 16

Describe the Coomb’s test for detecting auto-immune hemolytic anemia (AIHA) in a dog.

Answer 16

1. Take a blood sample from the dog.
2. Add anti-dog IgG (Coomb’s reagent) to the blood.
3. If agglutination occurs, this suggests that IgG was present on the dog’s RBCs.

Question 17

What kinds of molecules are red blood cell antigens?

Answer 17

Glycoproteins and glycolipids

Question 18

Learning Objective 3

Define natural antibodies.

Answer 18

Antibodies against foreign antigens found in an animal’s serum that are present even though the animal has never been exposed to that antigen.

IgM isotype

Question 19

Why are O blood type humans considered the universal donors?

Answer 19

O-type RBCs do not have antigens on their cell surface. Thus, they will not react with natural antibodies present in the blood recipient.

Question 20

If a human has type A blood (like Greg!), what kind of natural antibodies will be present in the serum?

Answer 20

Anti-B antibodies

Question 21

Does hypersensitivity to blood transfusions require a sensitization period (like in type 1 hypersensitivities) if natural antibodies are present?

Answer 21

Nope.

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.

Question 22

You have an exotic cat with type B blood. What would be the major concern with administering type A blood into this cat?

Answer 22

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.

Question 23

What is the difference between acquired antibody and natural antibody?

Answer 23

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.

Question 24

Learning Objective 4

Define cross match and blood typing and explain the tests used to determine each.

Answer 24

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.

Question 25

Why are AB cats considered the universal blood recipients?

Answer 25

AB cats do not have natural antibody against either A or B blood types.

Question 26

Can natural antibodies cross the placenta?

Answer 26

NO

Natural antibodies are IgM isotype, which are too large to cross the placenta.

Question 27

A type B mother cat has a type AB fetus in her uterus. Are you concerned for the health of this fetus?

Answer 27

Meh.

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.

Question 28

Identify the blood types of these cats.

Answer 28

Look for agglutination

Cat 1 - Type B

Cat 2 - Type A

Cat 3 - Type A

Cat 4 - Type A

Question 29

What clinical signs are you seeing in this foal?

Answer 29

Icterus

In this case, the symptoms are the result of hemolytic disease of the newborn. The icterus results from hemolysis and release of hemoglobin.

Question 30

How might a mare become sensitized to the RBC antigens of her foal that has an opposite antigen type?

Answer 30

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.

Question 31

Learning Objective 5

Explain the purpose for cross matching and blood typing and why they are important.

Answer 31

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.

Question 32

Learning Objective 6

Explain why blood typing and cross matching are especially important before a blood transfusion in some exotic breeds of cats.

Answer 32

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.

Question 33

Do dogs have natural antibodies against opposite blood types?

Answer 33

No.

Question 34

Learning Objective 7

Explain why it has been said that in the dog you can do one transfusion without a cross-match.

Answer 34

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.

Question 35

Learning Objective 8

Explain the factors that result in hemolytic disease of the newborn.

Answer 35

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.

Question 36

A mare is producing IgG against the erythrocyte antigens possessed by her foal in utero. SHOULD YOU START PANICKING?!?!

Answer 36

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.

Question 37

Learning Objective 9

Describe the major difference between hemolytic disease of the newborn in humans and in foals

Answer 37

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.

Question 38

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.

Answer 38

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.

Question 39

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.

Answer 39

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!