Biology 250 Lecture: “Talking Points” about Antigens, Antibodies, Agglutination, and Blood Typing
The entire idea of Antigen/Antibody complex formation (aka Agglutination) is at the root of the concept of Blood
Typing. So, let’s look at a few facts to help us clarify the inter-related nature of all of the above:
1) An antigen is a substance, usually a membrane (ie “surface”) protein, that has the ability to provoke an immune
response and the ability to react with the ANTIBODIES (or cells) that result from the immune response.
In fact, the term antigen comes from combining the two words that describe its function: that is, an antigen is
any substance which is “antibody generating”, hence antigen. (An alternate name for an antigen is agglutinogen).
2) ANTIBODIES are protein molecules produced by certain cells, as part of the immune response, against a
specific antigen. The ANTIBODIES combine with (they “latch onto”) that specific antigen to neutralize, inhibit,
or otherwise destroy it. (Another term for ANTIBODIES is IMMUNOGLOBULINS, or Ig’s) The combination of an ANTIBODY with the antigen for which it is specific is called an antigen/ANTIBODY complex ….
and the process of antigen/ANTIBODY-complex-formation is called agglutination. (An alternate name for an
ANTIBODY is agglutininin.)
3) Once antigen/ANTIBODY complexes form, they now “stick out” quite a long ways from the cell’s surface and
make the cells hang-up on each other as they pass by. This causes bunches of these similar cells to “clump-up”,
or agglutinate. Agglutination renders cells useless and easier for macrophages to come along, engulf large
quantities of them, and destroy/digest them.
4) An interesting biological factoid is that among most species, organisms possess antibodies to antigens they DO
NOT possess. Example: If you have antigens A, C and E – but NOT antigens B, D or F….then you would have Antibodies b, d, and f. You would NOT, of course, have antibodies a, c nor e….because you would NOT want to agglutinate
your own cells!! Organisms may be born with many of these antibodies; they may acquire some from nursing, or
they may manufacture many more upon exposure to various antigenic agents. (It is the activated B-lymphocytes,
maturing into plasma cells, that manufacture these antibodies or Igs ). Note: we will deal with the four types of ac-
quired immunity (Naturally acquired active and Naturally acquired passive; Artificially acquired active and
Artificially acquired passive) when we get to the Lymphatic/Immune System.
5) Before blood cells can be transfused, they must be typed and cross-matched so that transfusion reactions are
avoided. People have different blood types and transfusion of incompatible blood can be fatal. RBC cell
membranes, just as do ALL body cells, bear highly specific glycoproteins (antigens) on their external surfaces,
which identify each of us as unique from all others. One person’s RBC proteins may be recognized as foreign if
transfused into someone with a different RBC type, and the transfused cells may be agglutinated and destroyed.
At least 30 varieties of naturally occurring RBC antigens are common in humans. Besides these, perhaps 100
others occur in individual families (“private antigens”) rather than in the general population. The presence or
absence of each antigen allows each person’s blood cells to be classified into several different blood groups.
Antigens determining the ABO and Rh blood groups cause vigorous transfusion reactions (destroying foreign
erythrocytes) when they are improperly transfused. Thus, blood typing for these antigens is always done before
blood is transfused. Additional antigens (such as the M, N, Duffy, Kell, and Lewis factors) are mainly of legal
or academic importance. Because these factors cause weak or no transfusion reactions, blood is not specifically
typed for them unless the person is expected to need several transfusions, in which case the many weak transfusion reactions could have cumulative effects. The most important blood groups for RBC’s must be typed are
the ABO and Rh groups which will be described now.
6) As shown in Table 19.6 (P. 687) the ABO blood groups are named based on the presence or absence of two antigens: type A and type B. A person has blood type A if there are A antigens present on the RBCs membranes; blood type B if there are B antigens present on the RBCs membranes, blood type AB if there are BOTH
A antigens and B antigens on the RBCs membrane, and type O if there are NEITHER A antigens nor B antigens
on the RBCs membranes. (Note: this is read “O”, as in the letter “O”; but there is NO SUCH THING AS “O”
antigens. Hence, this really stands for “zero”, “zilch”, “nada”, “none” NO ANTIGENS!!)
7) The other “half” of the blood typing story involves the ANTIBODIES present in the plasma. Again, as shown in
Table 19.6, a person has the ANTIBODIES opposite of the antigens he/she possesses. That is, someone with
type A blood has anti-B antibodies; while someone with type B blood has anti-A antibodies; persons with type
AB would have neither antibody, those with type O blood would have BOTH anti-A and anti-B antibodies.
8) As for the Rh blood groups: there are at least eight different types of Rh antigens, each of which is called an Rh
factor. Only three of these, the C, D, and E antigens , are fairly common. The Rh blood typing system is so
named because one of the Rh antigens (antigen D) was originally identified in rhesus monkeys. Later, the same
antigen was discovered in humans. (If a person’s RBCs possess the Rh antigens, then he/she is “Rh-positive” (Rh+); if a
person’s RBCs lack the Rh antigens, then he/she is “Rh-negative” (Rh-). Most Americans (about 85%) are Rh+, meaning that their RBCs membranes carry the Rh antigen. As a rule, a person’s ABO and Rh blood groups are reported together: ie, O+, A-, AB+, and so on.
9) It should be added that unlike the ABO system, anti-Rh antibodies are not spontaneously formed in the blood of
Rh- individuals. (Refer back to #4 above that discussed the interesting fact that individuals form antibodies opposite the
antigens they possess, such that you might predict that Rh- individuals WOULD form Rh antibodies.) However, if an Rhperson receives Rh+ blood, the immune system becomes sensitized and begins producing anti-Rh antibodies
against the foreign antigen soon after the transfusion. Hemolysis does not occur after the first such transfusion
because it takes time for the body to react and start making antibodies; but the second time, and every time thereafter, a typical transfusion reaction occurs in which the recipient’s antibodies attack and rupture the donor RBCs.
10) An important problem related to the Rh factor occurs in pregnant Rh- women who carry an Rh+ fetus. The first
such pregnancy usually results in the delivery of a health baby. But, when bleeding occurs as the placenta detaches from the uterine lining, the mother may be sensitized by her baby’s Rh+ antigens that pass into her bloodstream. (Remember, during the course of the pregnancy itself, there is NO DIRECT CONTACT between Mother’s blood
and the fetus’ blood – this is because the PLACENTA is the “common organ” across which O2 + nutrients diffuse from
Mother’s blood to the fetus’ blood and across which CO2 + waste products diffuse from the fetus’ blood to the Mother’s
blood. It is only when there is bleeding in utero during the pregnancy or during delivery that the Mother may become sensitized to the Rh antigen and begin producing anti-Rh antibodies.) This is why Rh- women (A-, B-, AB-, O-) are
treated with a substance known as RhoGAM before or shortly after they have given birth (or if they have miscarried or aborted a fetus). RhoGAM is a serum containing anti-Rh antibodies. Because it agglutinates the Rh
factor, it blocks the mother’s immune response and prevents her sensitization to the Rh antigen (that she was exposed to via her Rh+ baby’s blood); thus her body does not produce any Rh antibodies. If the mother is NOT
treated with RhoGAM and becomes pregnant again with another Rh+ fetus, her anti-Rh antibodies will cross
the placenta from her blood into the fetus’ blood and destroy the fetus’s RBCs, producing a condition known as
hemolytic disease of the newborn (HDN) or erythroblastosis fetalis. (Remember, maternal and fetal bloods do NOT
come into contact with one another during a normal, uneventful pregnancy….but antibodies in the blood are small enough
to diffuse across the placenta ….and ATTACK the antigen for which they are specific! )
Why don’t Rh+ women have to concern themselves with being affected by erythroblastosis fetalis? Because
Rh+ women (and men, for that matter) NEVER form anti-Rh antibodies!! (If they did, their RBCs would agglutinate!)
11) When mismatched blood is infused, a transfusion reaction occurs in which the donor’s RBCs are attacked by
the recipient’s plasma antibodies. (Note: the donor’s plasma antibodies may also be agglutinating the host’s RBCs, but
they are so diluted in the recipient’s circulation that this does not usually present a serious problem.) The initial event,
agglutination of the foreign RBCs, clogs small blood vessels throughout the body. During the next few hours,
the clumped RBC’s begin to rupture or are destroyed by phagocytes, and their hemoglobin is released into the
bloodstream…when the rxn is exceptionally severe, the RBCs are lysed almost immediately. These events lead
to two easily recognized problems: (1) the O2 carrying capability of the transfused blood cells is disrupted, and
(2) the clumping of RBCs in small vessels hinders blood flow to tissues beyond those points. Less apparent,
but more devastating, is the consequence of hemoglobin escaping into the bloodstream. Circulating hemoglobin passes freely into the kidney tubules where it may precipitate, blocking the kidney tubules and causing
renal shutdown. If shutdown is complete (aka acute renal failure), the person may die! (Transfusion rxns can also
cause fever, chills, low blood pressure, rapid heartbeat, nausea, vomiting, and general toxicity; but in the absence of renal
shutdown, these rxns are rarely lethal. Tx of transfusion rxns is directed toward preventing kidney damage by infusing
alkaline fluids to dilute and dissolve the hgb and flush it out of the body. Diruretics, which ↑ urine output, are also given.)
12) Know how to work through a “Mystery Blood Type Typing” exercise. We go over these in 251-Lab.