Type II Hypersensitivity

What types of antigens are associated with mediating type II hypersensitivity

• Antigens associated with host cell membrane

• Intrinsic antigens

• Extrinsic antigens

What are intrinsic antigens?

Molecules synthesized by the cell

In what conditions are intrinsic antigens important?

autoimmune diseases & blood transfusion reactions

What are extrinsic antigens?

Molecules that attach to the cell

In what conditions are extrinsic antigens important?

microbial antigens and therapeutic drugs

Mechanisms of IgG in type II

• Target cell death

• Altered cell signaling/function

Mechanisms of target cell death

• opsonization/phagocytosis

• complement activation

• ADCC by NK cells

Mechanisms of altered cell signaling

• Antibody mediated inactivation

• Antibody mediated activation

What is an example of antibody-mediated inactivation?

myasthenia gravis

What is an example of antibody-mediated activation?

Grave’s disease

What is Grave’s disease?

An autoimmune disease of humans in which an antibody to thyroid-stimulating hormone receptor causes excess production of thyroid hormone

Examples of type II hypersensitivity

• immune mediated hemolytic anemia

• transfusion reactions

• neonatal isoerythrolysis

• immune-mediated thrombocytopenia

• myasthenia gravis

What is the most predominant blood group antigen in dogs?

Dog Erythrocyte Antigen (DEA)

Do dogs have naturally occurring antibodies against blood group antigens?

No

DEA in dogs is important for…

transfusion reactions

42% of dogs have what blood group antigen?

DEA 1+

What blood group antigens do felines have?

A, B, & AB

What is the response in a dog with DEA 1+ that receives DEA 1+ from a donor, or that has DEA 1- and receives DEA 1-?

Matched, no reaction

What is the response in a dog that has DEA 1+ and receives DEA 1- from a donor?

reaction unlikely

What would be the first response in a dog that has DEA 1- and receives DEA 1+ from a donor?

sensitization likely

What would be the second response in a dog that has DEA 1- and receives DEA 1+ from a donor?

reaction likely

What is the most prevalent blood group antigen in DSH/DLH felines?

A

In what felines is the blood group antigen B prevalent in?

certain breeds

What is the least prevalent blood group antigen in felines?

AB (<1%)

What antibodies are found in feline A blood?

weak IgM, IgG, anti-B

What antibodies are found in feline B blood?

Strong IgM, anti-A

What is the result of a cat with A blood receiving donor A blood?

Match, no reaction

What is the result of a cat with B blood receiving donor B blood?

Match, no reaction

What is the result of a cat with AB blood receiving donor AB blood?

Match, no reaction

What is the result of a cat with A blood receiving donor B blood?

At first exposure, severe reaction

What is the result of a cat with AB blood receiving donor B blood?

At first exposure, severe reaction

What is the result of a cat with B blood receiving donor A blood?

mild reaction possible

What is the result of a cat with AB blood receiving donor A blood?

mild reaction possible

What type of hemolysis occurs with transfusion reactions?

intravascular hemolysis

Causes of intravascular hemolysis

• complement-mediated lysis of RBCs

• phagocytosis of RBCs

• agglutination of RBCs

• coagulation system activation

Clinical signs of transfusion reactions

fever, restlessness, salivation, incontinence, shock

What is neonatal isoerythrolysis?

hemolytic disease in newborns

What percent of foals have different blood group antigens from the mare?

14%

What increases sensitization and increases chance of neonatal isoerythrolysis in newborns?

The mare having previous pregnancies

When does neonatal isoerythrolysis occur?

Wen maternal antibodies transferred in colostrum destroy neonatal red cells carrying paternal antigens

In what species is neonatal isoerythrolysis common?

horses, cats, mules

Clinical signs of neonatal isoerythrolysis

• depression

• weakness

• neuro signs

• icterus/jaundice

• hemoglobinuria

• acute anemia

What is immune-mediated thrombocytopenia?

Antibody-mediated platelet destruction can lead to spontaneous bleeding

What is myasthenia gravis?

Antibody-mediated blockade of specific cell-signaling pathways

What is Graves’ Disease?

Antibody-mediated stimulation of specific cell-signaling pathways

Diagnosis of type II hypersensitvity

• Laboratory tests for autoantibodies

• Blood group typing

• Compatibility assays

Management of type II hypersensitivity

• immunosuppressive therapy

• safe transfusion protocols

Treatment options for hemolytic anemia or thrombocytopenia

• immunosuppressive drugs

• transfusion of compatible blood or washed maternal red cells (foals)

• replacement therapies (commercial IgG preparations)