Human Blood Group System


The basis of human blood group system is the antigenic character of the Red cells. Red blood cell of the human being contains lipoprotein or glycoprotein on their surface which constitute the blood group antigens. About 300 blood group system so far discovered and some of the more common are____

  1. Natural           :
    • ABO (A, B)
    • MNS (M, N, S,s)
    • P (P­1, P, PK,P)
    • Lewis (Lea, Leb)
    • Luthern (Lua, Lub)
    • Ii (I, i) etc.
  2. Immune          :
    • Rhesus (C, c, D, d, E,e)
    • Kidd (JKa, JKb)
    • Duffy (Fya, Fyb)
    • Kell (K, k, Kpa, kpb, Jsa, Jsb) etc.

Of these only two blood group system ; ‘ABO’ and ‘Rhesus’ are of major clinical importance and constitute major antigens. Which causes serious complication in blood transfusion, hence they may be tested whenever blood is administrated. The other blood group systems are of less importance because the red cell antigens are weak and naturally occurring antibodies are encountered rarely.

Human Blood Group System :

Antigen (Agglutinogen) :

It is a protein or a carbohydrate which when introduce into the body; induces (evokes) specific immune responds either by producing specific antibody or special Sensitized ‘T’ Cell or both and which reacts specifically with the corresponding antibody in some detectable manner. In the Blood Group System all Antigens are present on the membrane of the Red Blood Cells.

Antibody (Agglutinine) :

Antibodies are define as a specialized serum protein that are formed in response to an antigen and reacts specially with that antigen or one very closely related to it in some observable manner.

They are two types :

  1. Natural Antibody :
    • Present normally in circulating blood (Serum or Plasma) since birth.
    • Does not produce by antigenic stimulation.
    • IgM in nature.
  2. Immune Antibody :
    • Not present in birth, only produce when RBC carrying the antigen are introduce into an individual, who normally lace the antigen. Example : Anti-D antibody.
    • IgG in nature.
    • Best reaction is done in 37°C temperature (body temperature).

Special Note : Immune antibody produce by various infection, Do not interfere with Blood Grouping procedure except Microplasma infection.

Microplasma pneumone, which produces cold agglutinin, responsible for haemagglutination for affected persons RBCs at 4°C.


The ‘ABO’ Blood Group System discovered by Landsteiner’s in 1901. The principle of Blood grouping is based on the Landsteiner’s Law.

Landsteiner’s Law :

   “The corresponding antibody is never present in the serum of an individual when the antigen is manifest on his red cells”. (Same type of antigen and antibody cannot stay together in an individual).

‘ABO’ Blood group system is divided into four major groups and they are ‘A’ group, ‘B’ group, ‘AB’ group and ‘O’ group. This depends on the presence of ‘A’ antigen or/and ‘B’ antigen on the surface of the Red Blood Corpuscles (RBCs) and determined by agglutination reactions obtained by mixing their Red blood cells with two different reagents (corresponding antibodies), known as Anti-A and Anti-B.

‘ABO’ Group is determined by two methods :

  1. Forward Grouping
  2. Reverse Grouping

  The percentage of different group in Indian & Caucasian (US) population as approximately as follows :

PopulationBlood Group
Caucasian (US)41090446

Antisera used in ‘ABO’ test procedure :

  • Purpose : Forward ‘ABO’ Blood Grouping.
  • Type of Antisera and Obtained from :
Type of AntiseraObtained From
Anti-AB‘O’ Group Blood
Anti-A‘B’ Group Blood
Anti-B‘A’ Group Blood
Anti-HLectin (Plant source)
Anti-A1‘B’ Group Blood or Plant lectin (Dolichos Biflorus
  • The titre of Antisera (Anti-A and Anti-B) should be at least 128.
  • The Antisera should not haemolysed red blood cells carring the corresponding antigen.
  • Every Antisera should be carefully tested for potency, avidity, specificity and freedom from rouleaux formation properties.
Human Blood Group Technique :

Antigen and Antibody present in ‘ABO’ Grouping :

 Blood GroupAntigenAntibody
ONoneAnti-A & Anti-B

Sub-group of ‘ABO” Blood Group System

Antigen ‘A’ primarily exists as a strongly reacting A1 antigen while A2 is a weakly reacting antigen found in a few persons.

The majority of Group ‘A’ infants appear to belong in subgroup A2 at birth which later become A1.


About 20% of Group-A / Group-AB are A2 or A2B; where as 80% is A1 or A1B.

The A2 antigen may give only weak reaction with the usual anti-A sera. A special Agglutinine (Ab) obtained from Seeds (Lectin) with the specificity of anti-A1 will agglutinate all A1 Cells but not A2 Cells.

Thus in a Reverse grouping if the serum of an ‘A’ group individual shows the presence of Anti-A; agglutinating A-Cells; the presence of A1 may be suspected. Then treat the ‘A’ Cells of individual with Anti-A1 lectin. If agglutination occurred hence individual’s Blood group A1. If agglutination not occurred then the individual Blood group is A2.

Antigen weaker than anti-A are occasionally encountered – called A3, Ax, Ay etc. These variations in ‘A’ antigen of erythrocytes are due to mutant form the Glycosyl Transferases produced by ‘A’ gene. Which are less efficient at transferring N-acetyl-D-galactosamine to H Substance.

Rhesus Blood Group System

In 1940 Landsteiner and Wiener reported that when the red cells of Macacus Rhesus monkeys were introduce into rabbits and guinea pigs, antibodies were evoked. These caused clumping not only of monkey’s red blood cells but also of the red blood cells of about 85% of human beings. The antigenic factor present on the surface of the human red blood cells called ‘Rh’ antigen.

‘Rh’ Blood group system is the second most important blood group system in human. ‘Rh’ Positive blood cells are antigenic for ‘Rh’ Negative individuals. Introduction of ‘Rh’ Positive cells (antigen) into an ‘Rh’ negative individual will stimulate the production of antibodies (anti-D) which will agglutinate and haemolysed ‘Rh’ Positive cells in 60 -70 cases.

‘Rh’ antibodies are not occurring naturally but develop only after exposure of an individual to antigen which the individuals lacks and the resultant antibody (IgG in nature), is called an immune antibody.

These antibodies act best at 37°C in protein (albumin) medium.

Rh’ Antigen :

  • Currently adopted nomenclature is Fisher-Race because it is easy to follow.
  • The ‘Rh’ blood group system is controlled by five co-dominant, closely linked allelic genes. These genes appear in three pairs – Cc, Dd, Ee.
  • Persons whose red cells possess D antigen are called ‘Rh’ Positive (irrespective of the presence or absence of other ‘Rh’ antigen). ‘Rh’ Negative person lacking the D antigen.
  • The other four antigen C, E, c, e are present in every individual in some combination. These antigen do not frequently produce strong reacting immune antibodies.
  • Rh allelic :
    1. CDE/CDE (Homozygous)
    2. CDE/cde (Heterozygous)
  • According to the Fisher-Race, three pairs of closely linked allelic genes gives rise to eight possible antigenic combinations____ cDe, CDe, cDE, CDE, cde, Cde, cdE, CdE.
  • Inheritance of ‘Rh’ group is independent of the ‘ABO’ group. In India approximately 95% population are ‘Rh’ Positive and 5% are ‘Rh’ Negative. Of ‘Rh’ Negative the frequency of ‘cde’ is higher , while the other pairs (Cde, cdE, cDe) are rare.
  • Anti-d does not exist and the presence of ‘d’ is indicated by the absence of ‘D’.

Rh’ Antibody :

  • Anti-Rh is an IgG immunoglobulin of lower molecular weight (1,70,000).
  • These are capable of crossing the placenta and can causes Haemolytic Disease of Newborn (HDN) in ‘Rh’ Negative mother , bearing an ‘Rh’ positive foetus.
  • Optimum visible immunologic reaction of these antibody with corresponding antigen take place at 37°C in the presence of protein(albumin).
  • About 50-75% of ‘Rh’ negative individual would be capable to produce anti-Rh when immunized with ‘Rh’ Positive cell (antigen), these are called Responder.

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