RH- System
The Objective : To give information about : 1- What RH blood group system means . 2- The inheritance of RH- system by two closely linked genes RHD and RHCE which located on chromosome 1 . 3- The importance of RH- system because RHD antibody of RH- system can cause disease called Erythroblastosis fetalis . 4- What Erythroblastosis fetalis means and how it is occur in first and second pregnancy . 5- Genetic transfer and recombination in bacteria through : * Transformation * Transduction : generalized and specialized . * Conjugation 6- How bacteria acquired new traits such as resistance to antibiotics .RH- System
RH blood types ( Rhesus factor ) were discovered in 1940 by Karl Landsteiner and Alexander Wiener . Like the ABO system , the RH system is defined on the basis of antigens that are present on erythrocyte surfaces . Rh factor is a protein found on most peoples RBCs .Inheritance : The RH locus is located on the long arm of chromosome 1 . It contains two closely linked genes RHD and RHCE . ( Table 1 ) . RH D gene codes for a single protein which contains the RH D antigen ( figure 1 )
Person with the DD or Dd genotype have the RH antigen ( D antigen) on their erythrocytes and are termed RH-Positive . ( Figure 1) . The recessive homozygotes , with genotype dd , are RH-Negative and do not have the RH antigen . Frequency in population RH Positive 85% , RH_Negative 15% .
Importance of RH system :
RH D antigen is the most immunogenic red cell antigen after A and B antigen . RH D antibody can cause hemolytic transfusion reactions and hemolytic disease of newborn or erythtoblastosis fetalis .Unlike the ABO system , in which antibodies normally are formed in response to antigens presented by other organisms , anti RH antibody production requires a stimlus by the human RH antigen itself . An RH-Negative person does not begin to produce anti-RH antibodies unless he or she is exposed to the RH antigen , usually through an incompatible blood transfusion or during pregnancy . Other important antigens in the Rh system are C, c , E , and e . These antigens are not usually tested for in routine blood typing tests , however , testing for the presence of these antigens is useful in paternity testing and when a technologist tries to identify unexpected Rh antibodies or find matching blood for a person with antibodies to one or more of these antigens .
RH-Maternal-fetal incompatibility : Results when an RH-Positive man and RH-Negative women produce RH-Positive children. Since RH+ father can have either a DD or Dd genotype , there are 2 mating combination possible . If the mans genotype is DD , all of their children will be RH-Positive and will have RH antigens on their erythrocytes . If the man is a heterozygote , with genotype Dd , half of their children will be RH-Positive , on average .
RH-Maternal-fetal incompatibility :
RH-Mother RH+father Children 1- dd ( homozygous ) DD Dd Dd all RH+ all at risk 2- dd ( heterozygous ) Dd Dd Dd dd dd . 1 RH+ : 1 RH-Only the RH+ children ( Dd ) are likely to have medical complications . When both the mother and her fetus are RH-Negative ( dd ) the birth will be normal .
Erythroblastosis fetalis ( Hemolytic Disease of Newborn HDN)
Type of anemia in which the RBCs of afetus are destroyed in a maternal immune reaction resulting from ablood group incompatibility between the fetus and its mother . This incompatibility arises when the fetus inherits a certain blood factor gene from the father that is absent in the mother .In the First Pregnancy with RH Positive child : This usually isn’t a problem, because very few of the fetus RBCs cross the placental barrier during pregnancy . At birth, or after an abortion or miscarrage RH positive RBCs from the baby enter the mothers blood stream . The mother immune system recognizes the cells as foreign and develops anti RH+ antibodies against them .
Figure (9)
In Subsequent Pregnancy with RH Positive baby : There is the risk that it will develop RH disease . anti RH antibodies in mother system can cross the placenta, bind antigen on RBCs of fetus and fetus RBCs are killed or ( hemolysis ) . The resulting anemia may be so profound that the fetus may die in utero . Reacting to the anemia, the fetal bone marrow may release Erythroblasts ( immature nucleated RBCs ) into the fetal peripheral circulation, causing Erythroblastosis fetalis. ( figure 2) In the fetus bilirubin, a breakdown product of RBCs accumulates, damaging the brain and turning the skin and whites of the eyes yellow, lead to jaundice
Peripheral blood film of fetus with Rh-Hemolytic disease of newborn showing large numbers of : Erythroblasts ( immature nucleated red blood cells ) Polychromasia Creneated cells .
Symptoms : Newborn jaundice Anemia Heart failure Enlarged Liver and Spleen . Generalized swelling Respiratory distress The infant may be stillborn or die shortly after birth .
Preventing Hemolytic Disease of Newborn (HDN):RH negative mother is givin injections of anti-RH D antibodies D gamma globulin called ( Rhogam ) around the 28 th week of pregnancy and again with in 72 hours after the delivery of the RH Positive baby . This must be done for the first and all subsequent pregnancies . The injected antibodies quickly agglutinate any fetal red blood cells as they enter the mother’s blood before they stimulate production of anti- RH antibodies .
ABO Hemolytic Disease of Newborn : :
ABO incompatibility disease is almost always limited to babies with A or B antigens whose mothers have type O blood . Approximately one third of these babies show evidence of the mothers antibodies in their blood stream but only a small percentage develop symptoms of ABO incompatibility disease . Group A and group B mothers usually have only IgM ABO antibodies . The majority of case of ABO HDN are caused by immune Ig G antibodies in group O mothers . ( Ig G which cross placenta while Ig M cannot cross the placenta ) . In contrast to Rh HDN , ABO disease may be found in the first pregnancy and may or may not affect subsequent pregnancies . Examination of the blood film of infants cells shows autoagglutination and spherocytosis . Polychromasia and erythroblastosis .Genetic Transfer and Recombination in Bacteria Genetic Transfer is a process whereby genetic material from one bacterium ( donor cell ) is transferred to a nother bacterium (recipient cell ) . Like sexual reproduction in eukaryotes, genetic transfer in bacteria is thought to enhance the genetic diversity of bacterial species . For example, a bacterial cell carrying a gene that provides antibiotic resistance may transfer this gene to another bacterial cell, allowing that bacterial cell to survive exposure to the antibiotic . In bacteria there are three different mechanism for transfer of genetic material : 1- Transformation 2- Transduction 3- Conjugation as in ( figure 1) and ( table 1 )
Figure 1-a
Figure 1-b
1- Transformation : The recipient cell takes up free DNA fragment released from donor cell . Transformation known to occur naturally and also used in genetic engineering in recombinant DNA study . and example of genes transferred by transformation the genes for polysaccharide capsule . Transformation Steps : 1- Donor DNA fragments binds to a cell surface receptor . (figure2) 2- An extracellular endonuclease cuts the DNA into smaller fragments . 3- One of the DNA strands is degraded and the other which contains the gene enters the bacterial cell . 4- The DNA strand is incorporated into the bacterial chromosome via homologous recombination ( crossing over ) .2- Transduction : Occur when bacterial genes are carried from a donor cell to a recipient cell by a bacterial virus ( bacteriophage ) . Facilitating subsequent recombination of the genetic markers of the two cells . Phage attaches to host cells receptors and injects DNA leaving the capsid outside . Inside the cell, viral DNA can either : a- Replicate to form phage and lyse the host to release the phage progeny ( process called lytic cycle ) . Or b- Integrate into the bacterial chromosome ( process called lysogenic cycle ) . Prophage : the viral DNA that integrates into the bacterial chromosome . ( figure 3 ) .
Some phage progeny released from the lytic may contain host DNA ( transducing phage ) which is transferred into a new host in the next infection cycle . The foreign host DNA can integrate by homologous recombination the process is called Generalized Transduction . The prophage may be exits from the bacterial chromosomes carrying small segment of host genes with it and enter the lytic cycle . Transducing phages infect anew host cells where recombination ( crossing over ) occur , the process is called Specialized Transduction . ( figure 4 )
Therefore there are two types of transduction : 1- Generalized Transduction : Each gene of the bacterial chromosome has equal chance to be transferred . ( randomally ) . 2- Sprcialized Transduction : Only genes adjacent to the prophage attachment site on the bacterial chromosome could be transferred . Genes transferred by transduction : Genes of toxins such as ( botulinum, diphtheria , cholera ) , genes of enzymes for sugar fermentation and genes of drug resistance .
3- Conjugation : Requires direct cell contact and involves the transfer of donor DNA to recipient cells through a conjugation tube that forms between the two cells .
Conjugation Steps :
1- F- plasmid carries tra genes which code for the production of a sex pilus ( a protein thread ) . ( figure 5 ) 2- When the tip of the sex pilus adhere to the cell wall of another cell, it pulls till the two cell, become bound together . 3- The F- plasmid nicked in one strand, where one parental strand passes to the recipient cell and the other remains in the donor cell . 4- Complementary strands are synthesized in both cells simultaneously during transfer .
Plasmid :is an extrachromosomal DNA molecule that can replicate independently of the main cellular chromosome , plasmid is a circular form of DNA .Types of Plasmids : 1- F- plasmid : the F factor responcible for DNA transfer during conjugation . 2- R- plasmid : DNA molecules carrying genes for resistance to various antibiotics and bacterial drugs . ( figure 6 ) 3- Col – plasmids : plasmid that code for proteins called colicine which kill sensitive E.coli cells . All known plasmids are circular molecule of DNA .
Genes transferred by Conjugation : Genes for drug resistance , resistance to metals , toxins production, enzymes, adherence molecules , degredation of toxic substances , uptake of iron . Some bacteria may also possess Trasposons or Jumping genes: that means genes or DNA segment that moves to a nother chromosome .