412 Chapter 13
type AB (with both A and B antigens), or type O (with nei-
ther A nor B antigens). Each person’s blood type—A, B,
or O—denotes the antigens present on the red blood cell sur-
face, which are the products of the genes (located on chromo-
some number 9) that code for these antigens.
Each person inherits two genes (one from each parent) that
control the production of the ABO antigens. The genes for A or
B antigens are dominant to the gene for O. The O gene is reces-
sive, simply because it doesn’t code for either the A or the B red
blood cell antigens. The genes for A and B are often shown as I A
and I B , and the recessive gene for O is shown as the lower-case i.
A person who is type A, therefore, may have inherited the A
gene from each parent (may have the genotype I A I A ), or the A
gene from one parent and the O gene from the other parent (and
thus have the genotype I A i). Likewise, a person who is type B
may have the genotype I B I B or I Bi. It follows that a type O per-
son inherited the O gene from each parent (has the genotype ii),
whereas a type AB person inherited the A gene from one parent
and the B gene from the other (there is no dominant-recessive
relationship between A and B).
The immune system exhibits tolerance to its own red blood
cell antigens. People who are type A, for example, do not pro-
duce anti-A antibodies. Surprisingly, however, they do make anti-
bodies against the B antigen and, conversely, people with blood
type B make antibodies against the A antigen ( fig. 13.5 ). This is
believed to result from the fact that antibodies made in response
to some common bacteria cross-react with the A or B antigens.
People who are type A, therefore, acquire antibodies that can
react with B antigens by exposure to these bacteria, but they do
not develop antibodies that can react with A antigens because tol-
erance mechanisms prevent this.
People who are type AB develop tolerance to both of these
antigens, and thus do not produce either anti-A or anti-B anti-
bodies. Those who are type O, by contrast, do not develop tol-
erance to either antigen; therefore, they have both anti-A and
anti-B antibodies in their plasma ( table 13.3 ).Transfusion Reactions
Before transfusions are performed, a major crossmatch is made
by mixing serum from the recipient with blood cells from the
donor. If the types do not match—if the donor is type A, for
example, and the recipient is type B—the recipient’s antibod-
ies attach to the donor’s red blood cells and form bridges that
cause the cells to clump together, or agglutinate ( figs. 13.5
and 13.6 ). Because of this agglutination reaction, the A and B
antigens are sometimes called agglutinogens, and the antibod-
ies against them are called agglutinins. Transfusion errors that
result in such agglutination can lead to blockage of small blood
vessels and cause hemolysis (rupture of red blood cells), which
may damage the kidneys and other organs.
In emergencies, type O blood has been given to people
who are type A, B, AB, or O. Because type O red blood cells
lack A and B antigens, the recipient’s antibodies cannot cause
agglutination of the donor red blood cells. Type O is, therefore,
a universal donor —but only as long as the volume of plasmaIron in food is absorbed in the duodenum (first region of
the small intestine) and passes into enterocytes (intestinal epi-
thelial cells), where it can be either stored or secreted into the
plasma through ferroportin membrane channels. Similarly,
the iron derived from the heme in old red blood cells that were
destroyed by macrophages can be stored in the macrophages or
released into the blood through ferroportin channels. Iron trav-
els in the blood is bound to a plasma protein called transferrin,
where it may be used by the bone marrow in erythropoiesis or
stored, primarily in the liver. Iron is eliminated from the body
only by the shedding of intestinal epithelial cells and through
menstruation. Thus, the intestinal absorption of iron must be
highly regulated so that only the amount needed to maintain
iron homeostasis is absorbed.
The major regulator of iron homeostasis is hepcidin, a
polypeptide hormone secreted by the liver. Hepcidin acts on the
enterocytes of the small intestine and the macrophages where
iron is stored to cause the ferroportin channels to be removed
from the plasma membrane and destroyed. Hepcidin thereby
inhibits the intestinal absorption of iron and the release of iron
from cellular storage, lowering the plasma iron concentration.
This completes a negative feedback loop in which the liver’s
production of hepcidin is decreased by iron deficiency and most
anemias, and increased by excessive iron intake.
Because the dietary requirements for iron are quite small,
iron-deficiency anemia in adults is usually due not to a dietary defi-
ciency but rather to blood loss, which reduces the amount of iron
that can be recycled. The normal dietary requirement for men is
about 10 mg/day, whereas women with average menstrual blood
loss need about 15 mg/day and pregnant women require about
30 mg/day.
Red Blood Cell Antigens and Blood Typing
There are certain molecules on the surfaces of all cells in the
body that can be recognized as foreign by the immune system
of another individual. These molecules are known as antigens.
As part of the immune response, particular lymphocytes secrete
a class of proteins called antibodies that bond in a specific fash-
ion with antigens. The specificity of antibodies for antigens is
analogous to the specificity of enzymes for their substrates,
and of receptor proteins for neurotransmitters and hormones. A
complete description of antibodies and antigens is provided in
chapter 15.
ABO System
The distinguishing antigens on other cells are far more varied
than the antigens on red blood cells. Red blood cell antigens,
however, are of extreme clinical importance because their types
must be matched between donors and recipients for blood trans-
fusions. There are several groups of red blood cell antigens, but
the major group is known as the ABO system. In terms of the
antigens present on the red blood cell surface, a person may be
type A (with only A antigens), type B (with only B antigens),