Download CHAPTER 8

Veterinary Immunology
Type II
Hypersensitivity
Dr. Chi-Young Wang

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
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

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

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)
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,
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

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
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
Hemolytic Disease of the Newborn
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)
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
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
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
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

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
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

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

Transfusion of A-positive blood into Anegative 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

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
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
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
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
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
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
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)
Type II Hypersensitivity
Reaction to Drugs

Third: cephalosporins may modify
RBC membrane that the cells
passively adsorb antibodies and
then removed by phagocytic cells
Type II Hypersensitivity Reaction
in Infectious Disease

Lipopolysaccharides, viruses such
as equine infectious anemia virus
and Aleutian disease virus,
Anaplasma, trypanosomes, and
Babesia
Type II Hypersensitivity Reaction
in Infectious Disease

Recognized as foreign and lysed by
antibody, complement or
phagocytosed by mononuclear
cells