Transcript 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