BLOOD TYPES
Distinct molecules called agglutinogens (a type of antigen) are attached to the surface of red blood cells. There are two different types of agglutinogens, type “A” and type “B”. Each type has different properties. The ABO blood type classification system uses the presence or absence of these molecules to categorize blood into four types.
Another level of specificity is added to blood type by examining the presence or absence of the Rh protein. Each blood type is either positive “+” (has the Rh protein) or negative “-” (no Rh protein). For example, a person whose blood type is “A positive” (A +), has both type A and Rh proteins on the surface of their red blood cells.
Blood types is the common of normal antigens signs, which are combined on immunologic and genetic bases.
There are
§ erythrocytes
§ leukocytes
§ serum blood types
Model of erythrocyte membranes with embedded molecules of different blood group systems. such systems currently known 25 (AB0, Rh, Cromer, Diego, Duffy, MNS, Lewis, etc.), and they include more than 500 different antigens.
History of the discovery of blood groups
In 1900, the Austrian physician Karl Landsteiner published the results of studies, which showed that all people have three blood types. Prague, Jan Jansky doctor found that people are not 3, and 4 blood groups and gave them refer to roman numerals: I, II, III, IV.
Agglutination (latin agglutinatio-adhesive)-this process is irreversible agglutination of red blood cells under the influence of antibodies. it is usually accompanied by hemolysis . the same happens in the bloodstream transfusion of incompatible blood.
Agglutination of red blood cells is the result of antigen-antibody reaction. In the erythrocyte membrane are complexes with antigenic properties. These antigenic complexes called agglutinogens. They interact with specific antibodies dissolved in plasma – agglutinins. Normally, blood is no agglutinins in their own erythrocytes.
The blood of every human individual contains a set of specific erythrocyte agglutinogens. Everyone has only her characteristic set of antigens.
In practice, now we take into account basically two antigenic systems – a AB0 and CDE.
Under this system, human erythrocytes are divided according to the antigenic structure into four groups:
· without antigen (now known that this antigen H), antigens A, B, AB.
Plasma under natural antibodies are conventionally denoted: αβ; β; α and missing.
Thus, people are distinguished combination of antigens and antibodies in the system AB0:
§ 0(I)αβ;
§ A(II)β;
§ B(III)α;
§ AB(IV).
Determination of blood in the System AB0 by standard serum
On clean white plane after their entries for glass, apply a standard serum first, second and third blood group two series. in each of drops of standard serum angle net of glass, make ten times smaller amount of blood, and after 2-3 minutes add one drop of saline. With the advent of agglutination observed within 5 minutes. Install blood type. In the case of four blood groups, conduct additional determination of standard serum group.
Determination of blood in the system AB0 by monoclonal antibodies
Pure white plane for glass divided into 4 sections: anti-a, anti-b, anti-d and control. Put in the relevant sector 1 drop of monoclonal antibodies anti-A, anti-B, anti-D and the control saline NaCl. Angle of glass makes ten times smaller amount of blood in two drops of monoclonal antibodies. Observed reaction on the plate shaking for 2.5 minutes.
System СDE (Rhesus)
At present, there are 6 major Rh antigens. For its designation in Europe adopted the nomenclature of Fisher-Race. According to it, the antigens are indicated by letters:
§ D, C, E, d, c, e.
Sometimes used Wiener nomenclature under which antigens are indicated:
§ Rh0; Rh ‘; Rh “; Hr0; hr’; hr”.
Often the two nomenclatures used simultaneously. Thus the symbols of the signs are in brackets:
§ Rh0 (D); rh ‘(C); rh “(E); Hr0 (d); hr’ (c); hr” (e).
Antigen Rh0 (D) – the main antigen of the Rh-system. It is found in red blood cells 85 % of people.
Based on the presence of erythrocyte antigen Rh0 (D) isolated Rh- positive blood. Human blood, red blood cells are devoid of this antigen relate to Rh-positive group.
antigen Rh0 (D) are unevenly distributed among the various races. In European populations, people with Rh-negative blood type make up 15%, mongoloid race – about 0.5%.
The main six of Rh antigens may often occur in combination:
CDE – 15,85 %;
CDe- 53, 2 %:
cDE- 14 , 58 %,
cde – 12,36%.
Natural antibodies to the Rh blood group system is not there. They can only be acquired, immune.
They are formed under special pregnancy when there is ingestion of Rh-negative women through the vessels of the placenta of Rh positive fetal red blood cells.
Mechanism of Rh-conflict in pregnancy
They can only be acquired, immune (during pregnancy when there is ingestion of Rh (-) women through the vessels of the placenta Rh (+) erythrocytes of the fetus).
Mechanism of Rh-conflict in pregnancy: immune antibodies formed in the body of Rh-negative women pregnant Rh-positive fetus, have the ability to cross the placenta into the body of the fetus, its cause hemolysis of erythrocytes. During labor in the blood of a newborn baby comes many antibodies and developed hemolytic disease. Antibodies can get newborn also with mother’s milk.
Leukocytes Blood Types
§ 1. common antigens of leukocytes (HLA-system)
§ 2. antigens of granulocytes.
§ 3. antigens of lymphocytes.
First data for leukocyte group received the French explorer Dausset in 1954 of open leukocyte antigen entered the science called «MAC».
Now there are more than 40 antigens of leukocytes, which are divided into three antigenic systems:
§ 1. common antigens of leukocytes.
§ 2. antigens granulocytes.
§ 3. antigens lymphocytes.
Common leukocyte antigens (system HLA-Human Leucocyte Antigene).
According to WHO recommendations using letter- numeric designation for antigens, whose existence is confirmed by a number of laboratories in parallel investigated antigens.
Genetically HLA- antigens are 4 subtypes (A, B, C, D), each of which combines allelic antigens. The most studied is A and B. For example:
§ HLA-A1,
§ HLA-A2,
§ HLA-A3,
§ HLA-A5,
§ HLA-A7,
§ HLA-A8.
For the first subspecies amount of antigen is 19, the second-20.
HLA antigens are also found in addition to leukocytes in the cells of various organs and tissues (skin, liver, kidney, spleen, etc.).
Mismatch of donor and recipient antigens after these reactions accompanied by the development of tissue incompatibility. Therefore, the installation of these antigens are used for tissue typing when choosing a transplant donor HLA-phenotype.
Antigens granulocytes
This system antigens characteristic only for cells of myeloid series, as in the bone marrow and blood .
3 known granulocyte antigens:
§ NA- 1;
§ NA- 2;
§ NB- 1,
That can be divided into 3 blood group antigen in this system.
Antibodies against granulocyte antigens cause short-term reduction in the number of neutrophils in the newborn.
If you do not take into account the total leukocyte antigens and antigens of granulocytes, you can post transfusion reactions due to the fact that in the plasma of the recipient it will be antibodies against antigens and as a result of their interaction allocated pyrogenic substances.
Lymphocyte antigens
Lymphocyte antigens present only into cells of lymphoid tissue.
Known until one antigen of the group, which is designated LYD1. It occurs in people with a frequency of about 36%. The value of these group antigens in transfusiology and transplantology is not fully studied.
Serum Group
The highest value among most whey serum proteins has genetic heterogeneity of immunoglobulin.
We know two immunoglobulin, there are: Gm and Inv. The system has more than 20 antigen levels, it means, that it has 20 blood group Gm (1) and Gm (2), etc., and the system Inv has a 3 antigens, it means, that it has 3 blood types : Inv (1), Inv (2), Inv (3).
Alpha -1 globulin.
In the area of alpha -1- globulin observed large polymorphism. Among them, were found 17 phenotypes of the system.
Alpha -2- globulins. In this section distinguish polymorphisms, including ceruloplasmin.
There are 4 types of ceruloplasmin (Cp):
· Cp A;
· Cp AB;
· Cp B;
· Cp DC.
Most commonly found group Cp B. In Europeans found 99 % of this group, and in negroid – in 94 % of cases.
Beta-globulins.
These include transferrin (Tf). It easily enters the compound of iron. The specified property provides the performance of important physiological functions – transport of iron to the bone marrow, where it is used for blood.
There are the following groups: TfC, TfD and others.
Transfusion of blood
We must transfused only blood of one groop with recipient!!!
Before the transfusion we must do the test on individual blood compatibility:
§ in AB0 system
§ in CDE system
§ biological test
The test of the compatibility AB0 system
The test of the compatibility AB0 system aimed at the detection of antibodies in the blood of the recipient to the donor’s RBC.
Sterile syringes collected from the vein of the recipient 1-3 ml of blood and carry it in a test tube containing a solution of citric acid – sodium. The tube is centrifuged. After, takes pipette with the serum of the recipient and shall put 2 drops on a plate. These drops of serum added to 10 times less of donor‘s blood. Shaking the plate 5 min., and then add 1-2 drops of 0.9 % solution of NaCl. The appearance of agglutination indicates that this blood must not be transfused.
Blood donor and recipient are not compatible in the system AB0.
Test of Rh compatibility aimed at detecting anti-erythrocyte Rh-antibodies.
In a Petri dish put the serum of the recipient. Add 10 times less of donor‘s blood. The mixture was stirred and heated in a water bath (temperature 45° C) for 10 min.
Present of agglutination indicating that blood incompatibility of Rh-factor.
The biological sample
Recipient pour 10-15 ml of blood, then stop the infusion and monitor its condition. if no violations of life, then after 3-5 minutes pour 10-15 ml of blood and re-infusion is stopped. Watch 5 minutes. Such manipulation is carried out for the third time. if the health of the recipient is not observed any violations of health, the blood can be transfused.
Physiological effects of transfused blood
§ 1.stimulating – stimulates the functions of various body systems and metabolic processes.
§ 2. hematopoietic – enhances blood.
§ 3. immunologic – strengthens the body’s defenses by introducing antibodies.
§ 4. nutrients effect – with blood enters nutrients.
groups substitutes are:
· hemodynamic – to normalize hemodynamic.
· detoxification- for the treatment of poisoning.
§ 3. preparations for parenteral nutrition:
§ • protein hydrolysates;
§ • solutions of amino acids;
§ • drugs fat emulsion.
§ 4. regulators of water and salt, and acid-base balance:
§ • saline;
§ • osmo diuretic.
§ 5. blood substitutes with the function of carrying oxygen.
§ 6. blood substitutes complex action.
Transfusion reactions resulting from Mismatched Blood Types
If donor blood of one blood type is transfused into a recipient who has another blood type, a transfusion reaction is likely to occur in which the red blood cells of the donor blood are agglutinated. It is rare that the transfused blood causes agglutination of the recipient’s cells, for the following reason: the plasma portion of the donor blood immediately becomes diluted by all the plasma of the recipient, thereby decreasing the titer of the infused agglutinins to a level usually too low to cause agglutination. Conversely, the small amount of infused blood does not significantly dilute the agglutinins in the recipient’s plasma. Therefore, the recipient’s agglutinins can still agglutinate the mismatched donor cells. As explained earlier, all transfusion reactions eventually cause either immediate hemolysis resulting from hemolysins or later hemolysis resulting from phagocytosis of agglutinated cells. The hemoglobin released from the red cells is then converted by the phagocytes into bilirubin and later excreted in the bile by the liver, as discussed in Chapter 70.The concentration of bilirubin in the body fluids often rises high enough to cause jaundice—that is, the person’s internal tissues and skin become colored with yellow bile pigment. But if liver function is normal, the bile pigment will be excreted into the intestines by way of the liver bile, so that jaundice usually does not appear in an adult person unless more than 400 milliliters of blood is hemolyzed in less than a day.
Acute Kidney Shutdown After Transfusion Reactions.
One of the most lethal effects of transfusion reactions is kidney failure, which can begin within a few minutes to few hours and continue until the person dies of
renal failure. The kidney shutdown seems to result from three causes: First, the antigen-antibody reaction of the transfusion reaction releases toxic substances from the hemolyzing blood that cause powerful renal vasoconstriction. Second, loss of circulating red cells in the recipient, along with production of toxic substances
from the hemolyzed cells and from the immune reaction, often causes circulatory shock. The arterial blood pressure falls very low, and renal blood flow and urine output decrease. Third, if the total amount of free hemoglobin released into the circulating blood is greater than the quantity that can bind with “haptoglobin” (a plasma protein that binds small amounts of hemoglobin), much of the excess leaks through the glomerular membranes into the kidney tubules. If this amount is still slight, it can be reabsorbed through the tubular epithelium into the blood and will cause no harm; if it is great, then only a small percentage is reabsorbed. Yet water continues to be reabsorbed, causing
TraNsplantation of tissues and organs
Most of the different antigens of red blood cells that cause transfusion reactions are widely present in other cells of the body as well, and each bodily tissues also has own additional complement of antigens. Consequently, any foreign cells transplanted anywhere in the body of a recipient can produce immune reactions. In other words, most recipients are just as able to resist invasion by foreign tissue cells as to resist invasion by foreign bacteria or red cells.
Autografts, Isografts, Allografts and Xenografts
Autografts, Isografts, Allografts, and Xenografts. A trans-plant of a tissue or whole organ from one part of the same animal to another part is called an autograft; from one identical twin to another, an isograft; from one human being to another or from any animal to another animal of the same species, an allograft; and from a lower animal to a human being or from an animal of one species to one of another species, a xenograft.
Transplantation of Cellular Tissues.
In the case of auto-grafts and isografts, cells in the transplant contain virtually the same types of antigens as in the tissues of the recipient and will almost always continue to live normally and indefinitely if an adequate blood supply is provided.
At the other extreme, in the case of xenografts, immune reactions almost always occur, causing death of the cells in the graft within 1 day to 5 weeks after transplantation unless some specific therapy is used to prevent the immune reactions.
Some of the different cellular tissues and organs that have been transplanted as allografts, either experimentally or for therapeutic purposes, from one person to another are skin, kidney, heart, liver, glandular tissue, bone marrow, and lung.With proper “matching” of tissues between persons, many kidney allografts have been successful for at least 5 to 15 years, and allograft liver and heart transplants for 1 to 15 years.
Attempts to Overcome Immune Reactions in Transplanted Tissue
Because of the extreme potential importance of trans-planting certain tissues and organs, serious attempts have been made to prevent antigen-antibody reactions associated with transplantation. The following specific procedures have met with some degrees of clinical or experimental success.
Tissue Typing—The HLA Complex of Antigens
The most important antigens for causing graft rejection are a complex called the HLA antigens. Six of these antigens are present on the tissue cell membranes of each person, but there are about 150 different HLA antigens to choose from. Therefore, this represents more than a trillion possible combinations. Consequently, it is virtually impossible for two persons, except in the case of identical twins, to have the same six HLA antigens. Development of significant immunity against any one of these antigens can cause graft rejection. The HLA antigens occur on the white blood cells as well as on the tissue cells. Therefore, tissue typing for these antigens is done on the membranes of lymphocytes that have been separated from the person’s blood. The lymphocytes are mixed with appropriate antisera and complement; after incubation, the cells are tested for membrane damage, usually by testing the rate of trans-membrane uptake by the lymphocytic cells of a special dye. Some of the HLA antigens are not severely antigenic, for which reason a precise match of some antigens between donor and recipient is not always essential to allow allograft acceptance. Therefore, by obtaining the best possible match between donor and recipient, the grafting procedure has become far less hazardous. The best success has been with tissue-type matches between siblings and between parent and child. The match in identical twins is exact, so that transplants between identical twins are almost never
rejected because of immune reactions.
Prevention of Graft Rejection by Suppressing
The Immune System
If the immune system were completely suppressed, graft rejection would not occur. In fact, in an occasional person who has serious depression of the immune system, grafts can be successful without the use of significant therapy to prevent rejection. But in the normal person, even with the best possible tissue typing, allografts seldom resist rejection for more than a few days or weeks without use of specific therapy to suppress the immune system. Furthermore, because the T cells are mainly the portion of the immune system important for killing grafted cells, their suppression is much more important than suppression of plasma antibodies. Some of the therapeutic agents that have been used for this purpose include the following:
1. Glucocorticoid hormones isolated from adrenal cortex glands (or drugs with glucocorticoid-like activity), which suppress the growth of all lymphoid tissue and, therefore, decrease formation of antibodies and T cells.
2. Various drugs that have a toxic effect on the lymphoid system and, therefore, block formation of antibodies and T cells, especially the drug azathioprine.
3. 3. Cyclosporine, which has a specific inhibitory effect on the formation of helper T cells and, therefore, is especially efficacious in blocking the T-cell rejection reaction. This has proved to be one of the most valuable of all the drugs because it does not depress some other portions of the immune
system.
Use of these agents often leaves the person unprotected from infectious disease; therefore, sometimes bacterial and viral infections become rampant. In addition, the incidence of cancer is several times as great in an immunosuppressed person, presumably because the immune system is important in destroying many early cancer cells before they can begin to proliferate. To summarize, transplantation of living tissues in human beings has had very limited but important success. When someone does finally succeed in blocking the immune response of the recipient without at the same time destroying the recipient’s specific immunity for disease, the story will change overnight.
