10 Biological properties of Ig

Dr. M. N. Gupta

  1. Objectives
  • To look at the biological functions of Ig
  • To understand how involvement of different classes of Ig in these functions are different
  • To develop a broad overview of the parts played by Ig during complete immune system

2. Concept Map

 

  1. Description

There is a reason why different classes of immunoglobulins exist. Each class, based upon its structure, localization (if any) can participate in a number of biological reactions. These properties also indicate the nature of interactive roles of Igs.

 

Proteins with same or very similar biological specificity are called isoproteins. Thus, we talk of isoenzymes or isolectins. Similarly, Antibodies differing in their structure but having the same specificity in terms of the antibodies are called isotypes.

 

Hence isotypes are essentially the five classes of Ig which we described earlier

 

One can also talk of isotypes in terms of Ig as an antigen itself. Antigenic determinants for a particular isotype are located at the constant region of Ig. Antigenic determinants for a particular isotype are shared by all Ig molecules in that particular class of Ig in a specie. Isotypes differ from specie to specie.

 

If we raise an antisera against an Ig (from an animal) this antibody in that sera will react with the Ig of the same class of all animals of that specie. Thus antibodies in the antisera are said to be isotypes which define Ig of that specie.

 

We have learnt that the five different classes, that is, isotypes differ in the structure of their H-chains. Serologically, these different H-chains constitute different antigens in size, carbohydrate content etc. In any antibody molecule, both chains are identical. The nature of the H-chain determines many biological properties of the antibody such as its half life. All isotypes have similar specificity. These may differ, however, in their properties to bind to receptors on other cells.

 

We have also learnt that IgG has 4 sub classes and IgA has two sub classes. These are also called subisotypes. These subisotypes differ in arrangement of interchain disulfide bridges as well as have difference in other structural features. Consequently there are differences in their functional properties.

The antisera obtained even against a simple antigen is very heterogeneous in terms of its antibody population and antibody specificity. Most antigens have multiple antigenic determinants and each determinant produces antibodies arising from triggering of more than one (many) B-cells. These antibodies will all react with the same epitope/antigenic determinant.

 

The antiserum also contains Ig molecules against past exposures to various antigens

 

Now as we have learnt, corresponding to each antibody, there are subclasses/isotypes and subisotypes (in case of IgG/IgA)

An antigen binding site on an antibody has the ability to bind with two or more diverse epitopes. This property is sometimes called redundancy. This ability of an antibody to cross react has important consequences.

We already know how cowpox scabs protected against small pox as proved by Jenner. So, many vaccines are possible because of this crossreactivity. This results in a less number of different antibodies required by an organism to defend against infections.

Think when you visit a shoe shop. The sizes of shoes are never an absolute fit with the feet of the customer. If that were so, the shoe shops will have to stock much larger number of shoes to cater to customers with different sizes (and shapes!) of feet.

 

Now, we will look at how different isotypes and in some cases subisotypes differ in their biological properties.

 

IgG molecules can agglutinate or clump particulate antigens such as blood cells and microorganisms. So, soluble multivalent antigens form precipitates while insoluble antigens form clumps. In both cases, the insoluble antigen-antibody complexes become the target of phagocytic cells and are destroyed. Hence, Agglutination (apart from a useful technique with many applications which we will learn in later module) serves the purpose of a defence mechanism as a part of the immune system response.

All IgG subisotypes except IgG2 can cross the placental barrier. IgG in fact is the only isotype which can do so. This enables the immune system of the mother to protect the growing foetus. Analysis of fetal immunoglobulins (of maternal origin since the foetus is not synthesizing antibodies) at the 3rd or 4th month of pregnancy shows a rapid rise in the level.

Hence, the foetus and the neonate is protected by the maternal IgG. Fc fragment is the enabler for placental passage as (Fab)2 or Fab are unable to cross placental barrier.

 

Blood ABO Compatibility

Type A blood has „A‟ surface antigen on RBC and plasma has antibodies against „B‟ antigens. Type B blood has „B‟ surface antigen on RBC and plasma with anti A antibodies. Type AB blood has both „A‟ and „B‟ surface antigens on RBC and plasma does not have antibodies against either A or B.

 

Type O blood has no surface antigens on RBC but plasma has both anti A and anti B antibodies.

 

Erythroblastosis fetalis

 

In 1930, Landsteiner observed that RBC from about 85% of humans agglutinated when rabbit antisera raised against rhesus monkey RBC was added. This was traced to the presence of a specific antigen on the surface of RBCs of this population. RBCs of the other 15 % humans did not have this surface antigen. This human RBC antigen was named Rh antigen. Around the sametime, two obstetricians had a case where a woman gave birth to a baby with haemolytic disease of the new born (erythroblastosis fetalis). The woman reportedly earlier had a severe reaction when given a transfusion of her husband‟s blood with the blood type. Luckily a collaboration between Landsteiner and these people ensued and it was found that while the husband had the same blood type under the ABO system, he was Rh+. Mother‟s blood was Rh-. The baby‟s blood was Rh+.

 

Subsequent work showed that in all cases of erythroblastosis fetalis, mother‟s blood was Rh-and baby‟s blood was Rh+. This happened when father had Rh+ blood. It was further found that mother‟s sera in such cases has antibodies against Rh+ antigen. These antibodies were of IgG isotype. So, these IgG crossed the placental barrier and reacted with the Rh+ RBC of the foetus (which had Rh antigen) and caused haemolysis. Small amount of Rh+ RBC from the foetus can cross the placental barrier. Immune system of the mother responds to these. This is normally too low titre to cause a problem. Hence, it is generally not a problem during the first pregnancy. During separation of the placenta, release of the cord blood into the mother exposes her to a large number of Rh+ RBC from the foetus. This produces large number of antibodies against Rh antigen in mother. Hence, during second and successive pregnancies, severe immune reaction occurs.

Rh antigen(s) are encoded by a single locus which has closely linked genes and many alleles. The various Rh antigens are Dce, DCE, DcE, Dce, dCe, dcE and dCE.

 

D antigen among all Rh antigens is the strongest immunogen and majority of the cases of the haemolytic diseases of the neonate are traced to the absence of this antigen in the mother. Administration of human anti-Rh antibodies within 72 h of posturition clears up the Rh+ cells from the mother‟s blood. Human IgG against the D antigen works in most of the cases.

Why similar incompatibility with ABO blood groups does not cause this problem?

 

In case of ABO incompatibility, immunoglobulins primarily are of IgM isotype and do not cross the placenta. IgG even if made are adsorbed by the placental tissues as these contain AB blood group substances. Rh antigen is not present in such tissues as Rh antigen is present only in RBCs.

 

Opsonization

 

Opsonin in Greek language means to prepare for eating! IgG coats the microorganism by recognizing various epitopes via its Fab portion. Many phagocytes including macrophages and PMN phagocytes have receptors for Fc portion and are thus able to recognize “ready for phagocytosis” micro organisms. Whole micro organism is engulfed and destroyed by the phagocytic cell.

Antibody dependant cell mediated cytotoxicity (ADCC)

 

In this case, large granular lymphocytes, macrophages or granulocytes bind to the IgG bound micro organism or a tumour. This binding is again via their receptors for Fc portion of the antibody. The cells destroy the microbe/tumour by releasing various substances (as explained earlier). Macrophages release enzyme and ROIs whereas LGLs use perforin and cytokines. NK cells mediated cytotoxicity operates similarly and is mediated by LGLs.

Neutralization of toxins

 

IgG is the preferred isotype for passive immunization against toxins such as tetanus and botulinus. We have discussed this before while discussing passive immunization

Immobilization of bacteria

 

IgG specific to the flagella and cilia of mobile bacteria cause them to clump. This prevents their ability to spread in the tissue and invade the adjoining tissues

 

Virus Neutralization

 

Both inhibition of viral attachment to the target cell (by IgG against viral coat protein) and inhibition of viral penetration or shedding of the viral coat (so that released DNA/RNA can lead to virus replication) is known.

 

Properties of IgA

 

The biological function of IgA is related to its presence in the secretions such as tears, saliva, colustrum,sweat and mucus. It is part of the mucosa associated lymphoid tissue (MALT). The secretory form is always a dimer. It is the major Ig synthesized in the body. IgA is bactericidal for gram negative bacteria in synergy with lysozyme. It is also antiviral and agglutinating Ig.

 

Properties of IgM

 

Elevated level of IgM reflects recent infection. Similarly, in foetus, these indicate congenital or pre natal infection (IgM is synthesized by the foetus after 5 months of pregnancy). Being pentameric, it is an efficient agglutinating antibody. IgM include natural isohaemagglutins.

 

Bacteria in Gastrointestinal and respiratory tracts have surface antigens. Antibodies formed against these cross react with A and B antigens of the RBCs. Thus, a person with A blood group have isohaemagglutins which cros react with RBCs of B blood group. This means blood transfusion requires ABO compatibility.

 

Properties of IgD and IgE

 

IgD

 

Present in serum in small quantities. It does not have any protective function in serum.

 

IgE

 

This class of Ig is involved in allergy/hypersensitivity. We will look at hypersensitivity in considerable detail in the subsequent modules.

 

Apart from just binding to antigens, antibodies carry out a number of functions. Most of these, of course, follow as a consequence of antigen binding to antibody. So, it sort of marks the antigen so that entire human immune system can focus on that antigen.