T2: Blood Physiology (Lecture 7)

Karl Landsteiner

-Observed human blood causes a severe reaction of hemolysis when randomly transfused

-Led him to discover that blood can be grouped into different types, A, B, AB and O.

2 systems for classifying blood

ABO and Rhesus

blood types determinant

antigens carried on the surface of red blood cells

ABO system Blood Types

Types A, B, AB and O

ABO class of antigens

carbohydrate molecules

Blood Antibodies

-found in blood (plasma)

-part of IgM class (Immunoglobin m): large & pentameric structure

-naturally occurring

-recognizes a unique molecule called an antigen; they combine to form an antigen-antibody complex

-A person does not make the same antibody type as the antigen they carry on their RBCs because an antigen-antibody complex would form, destroying their own antigens

Blood Type A Antigens & Antibodies

-antigen type A on the surface of the red blood cells

-anti-B antibodies

Blood Type B Antigens & Antibodies

-antigen B on the surface of the red blood cells

-anti-A antibodies

Blood Type AB Antigens & Antibodies

-both antigens A and B on the surface of the red blood cells

-no antibodies (no anti-A or anti-B antibodies)

Blood Type O Antigens & Antibodies

-no surface antigens of the ABO type on the surface of the red blood cells

- both anti-A and anti-B antibodies

Expression of ABO Antigens

ABO genes code for enzymes (proteins) of the ABO system which add on the specific carbohydrate molecules to the surface proteins of RBC

ABO hierarchy

genes A and B are dominant over O in heterozygous individuals

Blood Type A genotype

homozygous AA or a heterozygous AO

Blood Type B genotype

homozygous BB or a heterozygous BO

Blood Type AB genotype

AB genotype

Blood Type O genotype

- homozygous OO

Method of Determining Blood Type

-unknown sample separated into RBC & plasma fractions

-mixture of a sample of RBCs with a solution containing either anti-A or anti-B antibodies is observed for RBC agglutination (clumping)

Explain how each blood type could be observed

-Blood Type A: RBCs clump when anti-A antibody is added (have surface antigen A), but will not clump when anti-B antibody is added (no surface antigens B present)

-Blood Type B: Anti-B antibodies will clump RBCs (surface antigen B present), but there will be no clumping when anti-A antibodies are added

-AB blood type: clumping observed when either anti-A or anti-B antibodies added (surface antigens A & B present on RBCs)

-Blood type O: no clumping observed when either anti-A or anti-B antibodies are added (no surface antigens)

agglutination

process in which the surface antigens on RBCs are bound to antibodies to form a clump followed by hemolysis, or the rupture or destruction of the red blood cells

-when antigen & antibody aren't compatible (ex. antigen A + anti-A antibody)

When is blood transfusion essential?

During severe blood loss during surgical emergencies, trauma, or bleeding ulcers

Can blood be transferred from one person to another randomly?

-No, mismatched combinations of antibodies and antigens would result in agglutination of RBCs and hemolysis

-Now donors and recipients are matched before blood is transfused

What component of blood is transfused?

-In most blood banks, components are separated into packed RBC & platelet-rich plasma which is separated into PLT (platelet) concentration and FFP (fresh frozen plasma)

-In emergencies, whole blood can be used

Major cross match

a test in which a donor's red blood cell antigens are matched with the recipient's plasma antibodies; usually done when a donor's red blood cells are separated from the plasma fraction

Minor cross match

- done when whole blood is transfused where the red blood cells are not separated from the plasma, which contains antibodies

- the donor's plasma antibodies must also be matched with the recipients red blood cell antigens to prevent agglutination

best donor

one whose red blood cell antigens match with the recipients blood type

universal donors

-Blood donors with blood type O can donate blood to recipients with blood type A, B and AB in emergency situations

-Donors of blood type O do not possess any RBC antigens that can cause clumping by reacting with a recipient's plasma antibodies

universal recipients

-Blood recipients with blood type AB

-A donor of blood type AB can receive blood from all other ABO blood types in emergency situations

-Recipients of blood type AB do not possess any plasma antibodies that can cause clumping of the donor's red blood cell antigens

Mismatched blood transfusion (of the ABO Blood Types)

a transfusion reaction characterized by agglutination, or clumping of the red blood cells, and hemolysis (rupture of red blood cells) occurs

Classification of Rhesus (Rh) Blood Types

-Rh positive and Rh negative

- based on presence or absence of a protein on the surface of RBCs known as the D antigen

World-wide distribution of Rh Blood Types

Rh + is predominant

D-antigens

-found on RBC membranes

-protein molecules that form an integral part of the RBC membranes

-coded for by the dominant D genes

anti-D antibodies

-IgG class (Immunoglobin G)

-formed in the same manner by which our immune system reacts to exposure to a foreign bacterial antigen in developing antibodies

-only occur when an Rh negative individual is exposed to Rh+ blood with the D antigen

Dominant D gene

-codes for D antigens on red blood cell membrane

-Rh+ ve

No Dominant D gene

- absence of D antigen on red blood cell membrane

- Rh- ve

Rh+

- homozygous dominant genotype (DD) or heterozygous genotype (Dd)

- have D antigens on the surface of RBCs

- no anti-D antibodies in plasma

Rh-

- homozygous recessive (dd)

- lacks D antigens

- no anti-D antibodies in plasma

Exception of Lacking anti-D antibodies

-Rh- person develops anti-D antibodies when they are accidentally exposed to D antigens during a blood transfusion or during pregnancy, in the case of an Rh- woman.

Rhesus Mismatched Blood Transfusion

-Rh- person with no anti-D antibodies is exposed accidentally to Rh+ blood

-Rh- person develops anti-D antibodies

-When Rh- person is exposed by mistake to another transfusion of Rh+ blood, Anti-D antibodies will bind to Rh+ RBC and cause clumping and hemolysis

Rhesus Mismatch Between Mother and Child

-Rh- woman conceives a child with an Rh+ man, she will carry an Rh+ baby in her pregnancy

-During first pregnancy, mother's body is not exposed to baby's Rh antigen as the baby grows; baby is healthy

-During delivery, rupture of placental blood vessels causes fetal Rh+ RBCs to enter maternal blood, exposing baby's Rh+ blood to mother's immune system

-mother is sensitized to the Rh antigen and produces anti-D or anti-Rh antibodies

What occurs if a Rh- mother now producing anti-D/anti-Rh antibodies, becuase of her first pregnancy, becomes pregnant with a second Rh+ child

-circulating anti-D antibodies in the mother's blood pass through the placenta into the baby's body and bind to the baby's RBCs to cause rupture and hemolysis

- baby is born w hemolytic disease of the newborn (HDN)

hemolytic disease of the newborn (HDN)

- born with high levels of ruptured RBCs w enlarged spleens and jaundice due to breakdown of hemoglobin

Prevention of HDN

- by treating the mother immediately after her first delivery with anti-Rh antibodies which will bind to all the RBCs from the Rh+ newly delivered baby that are circulating in the mother's blood

- the baby's RBCs carrying D antigens are bound and blocked by anti-D antibodies and are not exposed to the mother's immune system to sensitize her