Veterinary Immunology

1. Veterinary Immunology Type II Hypersensitivity Dr. Chi-Young Wang

2. Most red cell-surface antigens are either glycoproteins or glycolipids • The ABO antigens are anion and glucose transporter proteins • If blood is transfused from one animal to another, the red cells

3. Type II Hypersensitivity antigens will stimulate an antibody response in the recipient • The rapid elimination of transfused red cells due to intravascular hemolysis by complement and extravascular destruction through mononuclear phagocyte system

4. The complexity of erythrocyte blood group system: L system to complex B system (cattle) • Some are soluble molecules in serum, salivia, blood fluids: J antigen (cattle); R antigen (sheep); dog erythrocyte antigen (DEA) 7

5. Animal make antibodies against foreign blood group antigens (this natural antibody) are derived from contact with foreign red cells or cross-reacting epitope (plants, bacteria, protozoa, and helminths)

6. Incompatible Transfusions • The recipient posses preexisting IgM antibodies to donor red cell antigens • Agglutination, hemolysis, or stimulate opsonization and phagocytosis of transfused cells • If no preexisting antibody,

7. Incompatible Transfusions circulate red cells induce antibodies later • Serious illness: mild febrile to death, hemoglobinemia, hemoglobinuria, blood clotting, DIC, anaphylatoxin production, mast cell degranulation, the vasoactive molecules, shock

8. Cross-matching test: blood cells from donor (without serum) are washed three times with saline. 2-4% suspension of red cells is made. These donor red cells are mixed with recipient serum and then incubated at 37 ℃ for 15-30 min • If lysed or agglutination: NO transfusion

9. Hemolytic Disease of the Newborn • Female animals become sensitized by incompatible blood transfusion or leakage of fetal red cells through the placenta • These anti-red cell antibodies are concentrated in colostrum • When the newborn suckles… destruction of RBC→HDN

10. Hemolytic Disease of the Newborn

11. Four Conditions for HDN • Young animal must inherit a red cell antigen from its sire that is not present in its mother • The mother must be sensitized to this RBC antigen • The mother’s response must be boosted (transplacental or repeated pregnancy) • Colostrum ingestion (high titers)

12. Sheep • Six blood group systems (A, B, C, D, M, and R) • B contains 52 alleles • R system: two soluble antigens, R and O, which are coded by alleles R and r • This R and O is controlled by gene I and its recessive allele I • If a homozygous I → neither R nor O

13. Epistatic Effect • The interaction between the I/i genes and the R-O system is called an epistatic effect; R and O are soluble antigens in the serum of II or Ii sheep

14. and are passively adsorbed onto red cells • Natural anti-R antibodies may be founded in R-negative sheep • M blood group (Mb antigen): an inhibitor of potassium transport

15. and are passively adsorbed onto red cells • Natural anti-R antibodies may be founded in R-negative sheep • M blood group (Mb antigen): an inhibitor of potassium transport

16. The antigen expressed on the surface of red blood cells-blood group antigens or erythrocyte antigens (EAs) • The expression of blood group antigens is controlled by genes located at different alleles

17. Pig • Sixteen pig blood systems (EAA-EAP) • The EAA system controls the expression of A and O antigens • Expression is regulated by S (secretor) with alleles S and s

18. In homozygous recessive state (ss) this gene can prevent the production of A and O • The amount of these antigens bound to red cells is undetectable • Not true antigen but soluble molecules in serum which absorbed onto red cells

20. Transfusion of A-positive blood into A-negative pigs leads to transient collapse and hemoglobinuria • HDN as a result of use of hog cholera vaccine containing pig blood • This vaccine consisted of pooled blood from viremic pigs activated with the dye crystal violet

21. Affected piglets may show rapidly progressive weakness and pallor of mucous membranes….longest survivors…show hemoglobinuria and janudice • EAE is also a complex system related to HDN

22. Dogs • Eight red cell antigens are recognized (DEA 1.1, 1.2, 3, 4, 5, 6, 7, and 8) • DEA1 is clinically important; 60% dogs express • No naturally occurring antibodies to DEA1.1 and 1.2 • Canine donors be negative for DEA1.1, 1.2, 3, 5, and 7

23. Dogs • A universal donor be negative for all the DEA except DEA4 • Unless the recipient is known, only universal donor can be used and a cross-match performed on all recipients

24. Dogs • A DEA 1.1-negative bitch is transfused with DEA 1.1-positive blood and subsequent bred to a DEA 1.1-positive male. The puppies develop a hemolytic anemia • The DEA 7 system is a soluble antigen like sheep R antigen

25. Dogs • A DEA 1.1-negative bitch is transfused with DEA 1.1-positive blood and subsequent bred to a DEA 1.1-positive male. The puppies develop a hemolytic anemia • The DEA 7 system is a soluble antigen like sheep R antigen

26. Parenting Testing • Examining the blood group antigens of an animal and its alleged parents • Since blood group antigens are inherited, they must be present on the red cells of one or both parents • Only exclude but never prove parentage

27. Type II Hypersensitivity Reaction to Drugs • First: the drug and antibody can activate complement, and RBC will be destroyed in a bystander effect • Second: penicillin, L-dopa, sulfonamide, and aminosalicylic acid may adsorb onto the surface of RBC; they may be recognized and eliminated (may be antibody)

28. Type II Hypersensitivity Reaction to Drugs • Third: cephalosporins may modify RBC membrane that the cells passively adsorb antibodies and then removed by phagocytic cells

29. Type II Hypersensitivity Reaction in Infectious Disease • Lipopolysaccharides, viruses such as equine infectious anemia virus and Aleutian disease virus, Anaplasma, trypanosomes, and Babesia

30. Type II Hypersensitivity Reaction in Infectious Disease • Recognized as foreign and lysed by antibody, complement or phagocytosed by mononuclear cells