Zoo 317 Heredity, Evolution and Society
|Lecture 30||Cummings 15: pp 366-370|
|BLOOD GROUPS; HISTOCOMPATIBILITY|
II. Rh blood groups.
III. Major histocompatibility complex
IV. Organ transplantation.
Page 369, paragraph 4: "...it is rare that anyone will be genetically identical to anyone else for the HLA genes." Except sibs. See III.E.
I. The ABO blood groups were the first antigens to be discovered on red blood cells (1900). Indeed, their discovery was a major landmark in the development of both immunology and genetics and provided the basis for understanding the rules that govern blood transfusions.
2. Landsteiner (1900) and other pioneers proved that there are three alleles: A, B, and O. A and B are codominant with respect to each other; both are dominant to O.
3. There is a corresponding antibody present in plasma for any ABO antigen that is not present on the red cells, e.g. a person with type A cells has anti-B but not anti-A.
C. The ABO blood groups are highly polymorphic among World populations. The frequencies of the three alleles vary considerably different populations. Indeed, it is the existence of polymorphism that allows us to recognize traits such as blood groups. If everyone were identical for a blood group antigen, then everyone would match everyone else. There are, in fact, antigens controlled by genes at other loci for which all but a few persons are identical. These few have been found because of unexpected transfusion reactions or HDN (see II.C).
2. Also in 1939, Al Wiener injected Rhesus monkey red cells into rabbits, leading to formation of antibodies that reacted with all Rhesus red cells and 85% of human red cells.
3. Comparison of the two systems showed them to be the same.
4. The system was named the Rhesus blood group, symbolized Rh.
C. HDN commonly occurs when an Rh mother carries a fetus that is Rh+.
2. Once immunized against Rh+ red cells, the mother's antibodies can cross into the fetal circulation in subsequent pregnancies and agglutinate Rh+ red cells.
3. HDN can be prevented by injecting anti-Rh+ antibodies into the Rh mother soon after she has delivered an Rh+ child.
2. Persons who receive multiple blood transfusions occasionally form antibodies to white blood cells. These human leukocyte antigens (HLA) were traced to variation at a complex locus on chromosome 6. They were shown to involve the same complex that was discovered in mice, and the general name major histocompatibility complex was applied to both.
C. MHC molecules are necessary for immune responses. In order for a T-cell to recognize an antigen, the antigen must be "presented" to it bound to an MHC molecule that is "self". MHC is also thought to play a role in developing immune tolerance.
D. The MHC is the most variable genetic region known. In humans, there are dozens of alleles at each of the three HLA Class I loci, designated A, B, and C. A large number also occur at the Class II loci, designated DP, DQ, and DR. Since recombination is very low within this short region (which is about 2 cM long), the allelic combinations (haplotypes) are transmitted as a unit. There are potentially many hundreds of haplotypes. The likelihood that a person would be homozygous for a particular haplotype is quite small except in the case of inbreeding.
E. Since the allele combination within a haplotype is transmitted as a unit, the haplotype complex can be treated as a single locus for purposes of analyzing transmission in families. For example, the four haplotypes that two parents might have can be represented as ab × cd. There would be four offspring combinations: ac, ad, bc, and bd. The likelihood that two sibs would match for MHC haplotypes is therefore 1/4.
F. Many disorders, expecially those that are thought to have an autoimmune component, occur more frequently in persons with certain MHC alleles than in other persons. The reasons for this are not known. However, the Class I and Class II gene products have important functions in immune response. It is possible that the various MHC alleles respond somewhat differently in the presence of a specific foreign antigen.
B. In the case of transplant of other organs, matching is carried out to avoid organ rejection by the recipient. Some mismatch may be tolerated, especially in the case of kidney transplants.
C. Matching of donors with recipients varies with the organ.
2. For other organs, the likelihood of a match with a relative or a stranger is very small. Nevertheless, heart, liver, and other organ transplants depend on the fortuitous near matches between donors, who are usually accident victims, and recipients.
|ABO blood groups||blood group compatibility||lyse|
|Rh blood groups||hemolytic disease of newborn||major histocompatibility complex|
|isogenic||human leukocyte antigens||glycoproteins|