Type II Hypersensitivities: 13th lecture لتحميل المحاضرة اضغط على الرابط التالي https://app.box.com/folder/0 Disorders in Immunity 3 Type II Hypersensitivities: Reactions Dr. Talib Hassan College of Medicine ThiQar University

13th lecture Type II hypersensitivities are a complex group of syndromes that involve complement-assisted destruction (lysis) of cells by antibodies (IgG and IgM) directed against those cells’ surface antigens. This category includes transfusion reactions and some types of autoimmunities. The cells targeted for destruction are often red blood cells, but other cells can be involved.

13th lecture HUMAN BLOOD TYPES RBCs receptors play essential roles in transport, recognition, and development, but they become medically important when the tissues of one person are placed into the body of another person. Blood transfusions and organ donations introduce alloantigens (molecules that differ in the same species) on donor cells that are recognized by the lymphocytes of the recipient. The immune system is in fact working normally, but it is not equipped to distinguish between the desirable foreign cells of a transplanted tissue and the undesirable ones of a microbe.

The basis of human ABO antigens 13th lecture The basis of human ABO antigens Karl Landsteiner, in 1904 found that the serum of one person could clump the red blood cells of another and he identified four distinct types, called the ABO blood groups. Like the MHC antigens on white blood cells, the ABO antigen markers on red blood cells are genetically determined and composed of glycoproteins. These ABO antigens are inherited as two (one from each parent) of three alternative alleles: A, B, or O. Their inheritance gives rise to four blood types (phenotypes), depending on the particular combination of genes. Thus, a person with an AA or AO genotype has type A blood; genotype BB or BO gives type B; genotype AB produces type AB; and genotype OO produces type O.

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Some important points about the blood types are: 13th lecture Some important points about the blood types are: (1) They are named for the dominant antigen(s). (2) The RBCs of type O persons have antigens, but not A and B antigens. (3) Tissues other than RBCs carry A and B antigens. The A and B genes each code for an enzyme that adds a terminal carbohydrate to RBC receptors during maturation. RBCs of type A contain an enzyme that adds N-acetylgalactosamine to the receptor; RBCs of type B have an enzyme that adds D-galactose; RBCs of type AB contain both enzymes that add both carbohydrates; and RBCs of type O lack the genes and enzymes to add a terminal molecule.

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ANTIBODIES AGAINST A AND B ANTIGENS 13th lecture ANTIBODIES AGAINST A AND B ANTIGENS The serum can contain antibodies that react with blood of another antigenic type, even though contact with this other blood type has never occurred!!!!!. Type A blood contains antibodies (anti-b) that react against the B antigens on type B and AB red blood cells. Type B blood contains antibodies (anti-a) that react with A antigen on type A and AB red blood cells. Type O blood contains antibodies against both A and B antigens. Type AB blood does not contain antibodies against either A or B antigens. What is the source of these anti-a and anti-b antibodies? It appears that they develop in early infancy because of exposure to certain heterophile antigens that are widely distributed in nature (surface molecules on bacteria and plant cells) that mimic the structure of A and B antigens. Exposure to these sources stimulates the production of corresponding antibodies.

Clinical Concerns in Transfusions 13th lecture Clinical Concerns in Transfusions The individual blood types of donor and recipient must be determined before giving blood transfusions. The general rule of compatibility is that the RBC antigens of the donor must not be agglutinated by antibodies in the recipient’s blood. Also blood samples must be cross-matched before the transfusion because other blood group incompatibilities can exist. This test involves mixing the blood of the donor with the serum of the recipient to check for agglutination.

13th lecture Interpretation of blood typing. In this test, a drop of blood is mixed with a specially prepared antiserum known to contain antibodies against the A, B, or Rh antigens. (a) If that particular antigen is not present, the red blood cells in that droplet do not agglutinate and form an even suspension. (b) If that antigen is present, agglutination occurs and the RBCs form visible clumps.

13th lecture Under certain circumstances (emergencies, the battlefield), type O blood lacks A and B antigens and will not be agglutinated by other blood types, so it could theoretically be used in any transfusion. Hence, a person with this blood type is called a universal donor. Because type AB blood lacks agglutinating antibodies, an individual with this blood could conceivably receive any type of blood. Type AB persons are consequently called universal recipients. conceivably تصوريا

13th lecture The severest reaction of blood incompatibility is massive hemolysis when the donated red blood cells react with recipient antibody and trigger the complement cascade. The resultant destruction of red cells leads to systemic shock and kidney failure brought on by the blockage of glomeruli (blood-filtering apparatus) by cell debris. Death is a common outcome. Other reactions caused by RBC destruction are fever, anemia, and jaundice. A transfusion reaction is managed by immediately halting the transfusion, administering drugs to remove hemoglobin from the blood, and beginning another transfusion with red blood cells of the correct type.

13th lecture Microscopic view of a transfusion reaction. (a) Incompatible blood. The red blood cells of the type A donor contain antigen A, while the serum of the type B recipient contains anti-a antibodies that can agglutinate donor cells. (b) Agglutination particles can block the circulation in vital organs. (c) Activation of the complement by antibody on the RBCs can cause hemolysis and anemia. This sort of incorrect transfusion is very rare because of the great care taken by blood banks to ensure a correct match.

THE RH FACTOR AND ITS CLINICAL IMPORTANCE 13th lecture THE RH FACTOR AND ITS CLINICAL IMPORTANCE The Rh factor (or D antigen) was first discovered when they found that rabbits inoculated with the RBCs of rhesus monkeys produced an antibody that also reacted with human RBCs. This monkey antigen (termed Rh for rhesus) was present in about 85% of humans and absent in the other 15%.

Rh inheritance in simplified as, a person’s Rh type results from a combination of two possible alleles a dominant one that codes for the factor and a recessive one that does not. A person inheriting at least one Rh gene will be Rh+; only those persons inheriting two recessive genes are Rh-. However, unlike the ABO antigens, exposure to normal flora does not sensitize Rh- persons to the Rh factor. The only ways one can develop antibodies against this factor are through placental sensitization or transfusion.

13th lecture Several patterns and their interpretations. Anti-a, anti-b, and anti-Rh are shorthand for the antiserum applied to the drops. (In general, O" is the most common blood type, and AB# is the rarest.)

Hemolytic Disease of the Newborn and Rh Incompatibility The placental sensitization occurs when a mother is Rh- and her unborn child is Rh+. The obvious intimacy between mother and fetus makes it possible for fetal RBCs to leak into the mother’s circulation during childbirth, when the detachment of the placenta creates avenues for fetal blood to enter the maternal circulation. intimacy الالفة

The mother’s immune system detects the foreign Rh factors on the fetal RBCs and is sensitized to them by producing antibodies and memory B cells. The first Rh+ child is usually not affected because the process begins so late in pregnancy that the child is born before maternal sensitization is completed. However, the mother’s immune system has been strongly primed for a second contact with this factor in a subsequent pregnancy.

13th lecture In the next pregnancy with an Rh+ fetus, fetal blood cells escape into the maternal circulation late in pregnancy and elicit a memory response. The fetus is at risk when the maternal anti-Rh antibodies cross the placenta into the fetal circulation, where they affix to fetal RBCs and cause complement-mediated lysis (hemolytic disease of the newborn (HDN) called erythroblastosis fetalis ). The immature nucleated RBCs are released into the infant’s circulation to compensate for the massive destruction of RBCs by maternal antibodies. Additional symptoms are severe anemia, jaundice, and enlarged spleen and liver elicit تظهر للعيان

13th lecture Maternal-fetal incompatibilities are also possible in the ABO blood group, but adverse reactions occur less frequently than with Rh sensitization because the antibodies to these blood group antigens are IgM rather than IgG and are unable to cross the placenta in large numbers. In fact, the maternal-fetal relationship is a fascinating instance of foreign tissue not being rejected, despite the extensive potential for contact. fascinating جذاب

Preventing Hemolytic Disease of the Newborn 13th lecture Preventing Hemolytic Disease of the Newborn If the mother Rh- and the father is Rh+, the probability that the child will be Rh+ is 50% or 100%, depending on the exact genetic makeup of the father. If there is any possibility that the fetus is Rh+, the mother must be passively immunized with antiserum containing antibodies against the Rh factor (Rho [D] immune globulin, or RhoGAM). This antiserum, injected at 28 to 32 weeks and again immediately after delivery, reacts with any fetal RBCs that have escaped into the maternal circulation. It is ineffective if the mother has already been sensitized by a prior Rh+ fetus or an incorrect blood transfusion, which can be determined by a serological test.

13th lecture Prevention of erythroblastosis fetalis with anti-Rh immune globulin (RhoGAM). Injecting a mother who is at risk with RhoGAM during her first Rh" pregnancy helps to inactivate and remove the fetal Rh-positive cells before her immune system can react and develop sensitivity.

13th lecture OTHER RBC ANTIGENS About 20 other red blood cell antigen groups have been discovered. Examples are the MN, Ss, Kell, and P blood groups. Because of incompatibilities that these blood groups present, transfused blood is screened to prevent possible cross-reactions. The study of these blood antigens (as well as ABO and Rh) has given rise to other useful applications. For example, they can be useful in forensic medicine (crime detection), studying ethnic ancestry, tracing prehistoric migrations in anthropology. Many blood cell antigens are remarkably hardy and can be detected in dried blood stains, semen, and saliva. Even the 2,000-year-old mummy of King Tutankhamen has been typed A2MN! remarkably لافت للنظر