This is how I’m going to structure things (at least until I figure out a better way or someone asks a question): I have gotten my hands on a variety of old GRE subject tests, and I have gone through them and read the questions. During my study groups, I have the students take practice tests and we go over the answers. I’m going to post one (or two or three) question(s) that are about a particular subject, then explain the concepts that are involved. How’s that? Good! Let’s get started.
Question: A homozygous, Rh-positive man (RR) marries an Rh-negative (rr) woman. Their first child is normal, but their second child has hemolytic disease (Rh disease). The first child did not have hemolytic disease because….
Alright–this questions is mostly about the Rh factor and its effect on the unborn child. First: the vocab of this question.
Homozygous–the condition of having two identical alleles for a particular gene
Rh-factor–a specific antigen present on the surface of the red blood cell
Hemolytic disease–a condition in which the red blood cells of an Rh-positive fetus or newborn are destroyed by anti-Rh antibodies previously produced in the bloodstream of an Rh-negative mother.
The first thing you need to do when reading a question about biology is to dissect the question itself. This questions has a lot of vocab and parenthesis that may cause confusion. Read the question at least twice to get at the real meat. The question introduces you to a couple with, now, two children. We learn the genotype (genetic makeup) of the parents: both are homozygous for the Rh-factor; dad is homozygous dominant for the Rh-factor, while mom is homozygous recessive.
The question is really testing your knowledge of red blood cells and the antigens present on the cells. An antigen is anything that causes an immune response. Every person has a blood type depending up on the glycoproteins (carbohydrates attached to proteins) attached to the red blood cell membrane. The lucky person who discovered these glycoproteins decided to give each type a letter: A or B. A person who has glycoprotein “A” on his blood cells has type A blood. A person who has glycoprotein “B” has type B blood. A person who has both glycoproteins on his blood cells has type AB blood, and a person with neither of these glycoproteins has type O blood.
What these blood types are missing is that “+” or “-” that you all see on your birth certificate. The positive or negative is called the Rh-factor, and either you have it or you don’t. “Rh” stands for rhesus, and was named for the rhesus monkey, which is where the protein was first noticed. This protein reacts just like the other glycoproteins on your blood cells–if your body recognizes the antigen (glycoprotein) then it will not attack it. If your body doesn’t recognize the antigen, then it will initiate the non specific and specific defenses to attack the perceived threat. If this was the first time your body saw the antigen, the non specific defenses would take care of the problem, while the specific defenses created antibodies to protect the body from future invasions. (Well, actually it’s a bit more complicated than that, but I’ll go into the intricacies of immuno-defense in a later post).
Your blood type becomes important when you need blood from a donor, or you are donating blood to someone who needs it. In the case of an emergency, hospitals use type 0- blood, since these red blood cells have no antigens on them at all, any person will accept this blood into his veins without triggering the immune system. This same idea applies to the transfer of blood from mother to child.
During most of pregnancy, the fetal circulatory system is closed off from the mother’s circulatory system. The fetus produces its own red blood cells, which accept oxygen and nutrients from the mother’s blood stream via capillaries in the placenta. The mother’s red blood cells do not cross over to the fetus, and the fetus’s red blood cells do not cross into the mother’s blood stream. During the trauma of birth, however, blood exchange happens. This usually isn’t that big of a deal, however. Even if the baby’s blood type is different from the mom’s, mom’s immune system will take care of any foreign blood cells quickly (and produce antibodies against future invasion from these blood cells). A problem arises only during the second pregnancy and in relation to the Rh-factor.
If mom is Rh-positive, it doesn’t matter what her child is (Rh-negative or Rh-positive) her body will not react to the child’s blood during birth. Her immune system will recognize the Rh protein, and therefore not attack a cell that is Rh positive. If it encounters a cell without the Rh-factor, it won’t recognize the cell as foreign because it is the protein present on the cell’s membrane that identifies it as foreign. If there’s no protein, there’s no problem. However, if mom is Rh-negative, her body will recognize any Rh-positive blood cell as foreign, and activate her immune system accordingly. The Rh-factor is passed on via normal Mendelian genetics, with Rh-positive being dominant and Rh-negative being recessive. Therefore, it is possible to determine the possible genotypes of the child in regards to the Rh-factor using a simple Punnett square.
r Rr Rr
r Rr Rr
If mom is Rh-negative, as she is in this GRE question, then her first pregnancy will proceed normally. No matter what the blood type of her baby, her blood won’t come in contact with the baby’s blood cells (and therefore any possible antigens) until birth. After birth, the baby is pretty much safe from any antibodies mom’s immune system produces. The problem arises when mom and dad want to give junior a little brother or sister. If mom is Rh-negative and bundle-of-joy #1 is Rh-positive, mom’s immune system gets exposed to the Rh antigen. Her immune system reacts accordingly, destroying the perceived threat, and producing antibodies to protect her against future invasions. If bundle-of-joy #2 is also Rh-positive, mom is already primed and ready to kill off any Rh proteins she sees. Red blood cells don’t cross over the placental barrier, but antibodies do. Can you see the problem? Mom’s antibodies attack the fetus’s red blood cells, causing the fetus to die from lack of oxygen and nutrients, or causing the baby to be born severely anemic. This condition is called “hemolytic disease of the newborn.” Look familiar? Yep! This is the disease to which the question is referring.
So, now that we know the basics, let’s get back to the question:
A homozygous Rh-positive man marries an Rh-negative woman. Their first child is normal, but their second child has hemolytic disease.
This part makes sense, doesn’t it? We know the genotype of both mom and dad, so we can use a Punnett square to predict all the possible genotypes of the children: Rr, Rr, Rr, and Rr.
It appears that all the children will be heterozygous for Rh-positive. Now, we know that there may be a problem between an Rh-negative mother and an Rh-positive fetus due to mom’s immune system. However, mom’s immune system is not exposed to the Rh antigen until the moment of the first baby’s birth, so baby #1 is protected. When mom gets pregnant again, though, the child is afflicted by hemolytic disease. “Hemo” refers to blood, while “lytic” refers to bursting; “hemolytic” is the bursting of red blood cells. Bad! This occurs because mom’s immune system is primed and ready to kill off the Rh-antigen the moment it sees it, so baby #2 is attacked as soon as he begins to make red blood cells.
Good! So there is the main concept behind the question. Let’s get to the actual question part, though:
The first child did not have hemolytic disease because….
Well, can you answer the question? Yep, the first child didn’t have hemolytic disease because mom’s immune system had not yet been exposed to the Rh-antigen and therefore did not have any antibodies capable of crossing the placental barrier and attacking the fetus’s red blood cells.
Here are the multiple choice answers given to this question:
A) the child was heterozygous (Rr)
B) the child lacked the Rh antigens
C) the mother had a previous blood transfusion that protected the child against antibodies
D) anti-Rh antibodies present in the mother were destroyed by the child’s immune system
E) anti-Rh antibodies were not induced in the mother until the delivery of the child
So, given what we know, the answer to this question is E. Yes, the child was heterozygous (Rr), but this does not answer the question, and is not the reason the child did not have hemolytic disease. Because the child was Rr, we know he had the Rh antigens (remember Rh-positive is the dominant trait), so answer B doesn’t even make sense. Answer “C” just seems ridiculous to me, and hopefully to you, too. Blood transfusions don’t change the mom’s immune system, nor what diseases she is protected against. A blood transfusion is primarily used to ensure the presence of adequate red blood cells and blood volume in the circulatory system. It has nothing to do with protecting a fetus against antibodies. The growing fetus is still building its immune system, so he must rely on mom for protection and immunity. He doesn’t yet have the capacity to fight off foreign cells, so he has no defense against mom’s antibodies. Therefore, option “E” is the correct answer!
How is it, then, that Rh-negative moms have more than one child? Why aren’t they all still born? Scientists attacked the problem of hemolytic disease some time ago. One of the first questions a doctor asks a pregnant couple is their blood types. If mom is Rh-negative and dad is Rh-positive, then during the birth (or soon thereafter) mom will be injected with a serum named RhoGAM, which contains antibodies against the Rh antigen. This serum takes care of any Rh-positive red blood cells circulating in mom’s blood, so her immune system doesn’t have the chance to get all annoyed. She doesn’t make any of her own antibodies against the Rh antigen, and her future children are protected.
Questions? Comments? I hope this helped!