Antibodies and Vaccination

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Antibodies and Vaccination

Introduction

Antibodies are plasma proteins that are found in the blood of vertebrates. They are a component of the immune system that protects the bodies of living organisms against harmful disease-causing agents. Different foreign organisms enter our bodies while we are performing daily life activities. Antibodies and other components of the immune system protect our bodies against the harmful effects of these foreign organisms.

Antibodies are produced by plasma cells in response to exposure to an antigen. Antigens are the molecules that, once exposed to the immune system, causes the production of antibodies against themselves. One antibody is formed against one specific antigen. When the antigen enters the body, it is recognized by the antibodies directed against it, bound, and is later destroyed by recruiting the other components of the immune system.

Five different classes of antibodies are found in humans. Each class has its own functions and plays a specific role in the protection of the body.

Vaccination is a process by which an agent is injected into the body that stimulates the synthesis of certain antibodies. In some instances, antibodies directly may also be injected into the bodies during the vaccination process.

In this article, we will talk about the synthesis of antibodies, their nature, mechanism of action, types, and functions, as well as clinical conditions associated with them. In addition, we will also talk about vaccination, its types as well as its medical significance.

Synthesis of Antibodies

As stated earlier, antibodies are formed by the plasma cells. These cells arise from B lymphocytes during their processing in the bone marrow and liver. Thus, the synthesis of antibodies involves preprocessing of B lymphocytes, formation and activation of B cell clone, and formation of antibodies by plasma cells.

Processing of B lymphocytes

Like other blood cells, B lymphocytes are also made within the bone marrow during the process of hematopoiesis. It takes place in the yolk sac, liver, and spleen during intrauterine life.

B lymphocytes are preprocessed in the liver during the early fetal life and are in bone marrow during the rest of fetal life as well as after birth.

B lymphocytes have great diversity as compared to the t lymphocytes. Millions of multiple types of antibodies are formed by B cells having different reactivities. Each type of antibody formed requires a specific type of B cells.

After preprocessing, B cells migrate to the lymphoid tissues present in the body, such as lymph nodes and spleen. Here, they form clones that are later activated to form plasma cells that produce antibodies.

Formation and Activation of Clone

When a specific antigen enters the body, it is taken by the blood or the lymph to the nearest lymphoid tissue. When it comes in contact with B lymphocytes, certain specific antibodies are formed that are directed against it.

Millions of multiple types of preformed B cells are present in the lymphoid tissues. Each of these preformed cells is capable of forming only one specific type of antibody. Also, one cell can only be activated by its own specific type of antigen.

Once a B lymphocyte is activated by an antigen in the lymphoid tissue, it reproduces multiple times to form similar copies. All the new cells thus formed are capable of producing and secreting the same specific antibody. All these lymphocytes that are capable of forming one specific type of antibody are collectively called a clone of lymphocytes.

The clone becomes activated when the same antigen again enters the body and comes in contact with the members of the clone.

Formation of Antibodies by Plasma Cells

The clones of B lymphocytes remain dormant in the lymphoid tissues in the absence of the specific antigen. Once a specific antigen enters the body, it is phagocytosed by macrophages that present the antigen to the B lymphocytes and activate the clone. The same antigen is also presented to the T lymphocytes that activate and form helper T lymphocytes. These helper cells assist the process of B lymphocytes.

B lymphocytes activated by the antigen enlarge to form lymphoblast. Some of these lymphoblasts differentiate to form plasmablasts, the precursors of plasma cells.

The cytoplasm of plasmablasts expands to form expand along with the proliferation of rough endoplasmic reticulum. The plasmablasts then undergo mitosis and form multiple small cells called plasma cells. Each plasmablast gives rise to 500 plasma cells.

These plasma cells then produce antibodies by the process of translation. The antibodies thus formed are secreted by plasma cells into the lymph and are later carried into the blood.

Structure of Antibodies

Antibodies are also called immunoglobulins or gamma globulins. Recall that antibodies are proteins in nature. Each antibody is made up of a combination of polypeptide chains, light and heavy chains.

Each antibody is made up of two light chains and two heavy chains. Each heavy chain is paired with one light chain at one of its ends. The two chains are linked together via disulfide bridges between the side chains of component amino acids.

Each light chain and heavy chain has two portions, a constant portion and a variable portion. The variable portion is different for each specific antibody. It is the portion by which an antibody recognizes and attaches to its specific antigen.

The constant portion, on the other hand, is same for all the antibodies present in our blood. It determines the general properties of antibodies like the ability to diffuse through the tissues, adherence to specific structures, etc.

Specificity of Antibodies

Recall that each antibody is specific for one particular antigen. This specificity is due to the specific arrangement of amino acids in the variable portions of light and heavy chains. The specific amino acid arrangement has a steric shape for each different antigen. The specific antigen that binds to the antibody has prosthetic groups that are the mirror image of the amino acid arranged in the variable portions.

The antigen-antibody complex formed between the highly specific antibody and antigen is very strong and is held together by the following types of bonds.

  • Hydrophobic interaction
  • Hydrogen bonding
  • Ionic attraction
  • Van der Waals forces

Mechanism of Action

Antibodies are an important component of the immune system. They perform their action in two different ways. One is the direct method in which antibodies act directly on the invading agent. The other one is the indirect method in which antibodies act by activating the complement system. A brief detail of both these methods is as follows.

Direct Method

The invading agent has multiple binding sites for antibodies to attach. In the indirect method, antibodies get attached to one of these binding sites and inactivate the foreign agent. They do so in one of the following ways.

Agglutination

Some invading agents have multiple binding sites such as bacteria, red blood cells, etc. In this case, antibodies bind to these multiple binding sites and cause these large particles to clump together. This process is called agglutination.

Precipitation

In some cases, antigen molecules are very large. The antigen-antibody complexes thus formed become so large that they are rendered insoluble. These complexes precipitate, and the invading agent becomes inactive.

Neutralization

It is another method of inactivating the invading agent. It takes place in the case of foreign agents having toxic sites. In such situations, antibodies bind and cover the toxic site, thus neutralizing the foreign particle.

Lysis

In some cases, antibodies directly attack the membrane components of foreign cellular particles. Thus, they cause lysis of the cells, inactivating them. It is seen in the case of some highly potent antibodies.

It must be noted that the direct action of antibodies is not that effective in protecting the body against foreign particles. The indirect method is much better in providing protection to the body, as described below.

Indirect Action

The complement system is the most important example of the indirect action of antibodies. It is a system of 20 or more proteins, some of which are activating enzymes that activate the main actor proteins. The proteins of the complement system are normally present in plasma but are in their inactive form. The enzyme precursors that are necessary for the action of these complement proteins can be activated by classical or some other pathways.

Classical Pathway

This pathway of activating the complement system is initiated by the antigen-antibody complex. The complex activates the C1 protein that in turn starts a cascade of reactions, causing activation of other proteins of the complement system. These proteins then perform the action of protecting the body against the harmful invading agents.

Some of the actions performed by these activated complement proteins are discussed below.

Opsonization and Phagocytosis

Opsonization is a process by which certain bacteria or other particles are labelled for phagocytosis. One of the products of the complement system enhances the phagocytosis by neutrophils and macrophages by causing them to engulf cells to which antigen-antibody complexes are attached. This process enhances the number of bacteria that can be phagocytosed by a hundredfold.

Lysis

One of the products of the complement complex is the lytic complex. It is a combination of multiple proteins. This lytic complex has a direct effect on bacteria and other cellular agents and can cause rupturing of cell membranes.

Agglutination

It is different from the agglutination caused by the direct method. In this case, the products of the complement system change the surfaces of the foreign agents, causing them to adhere to one another. In this way, agglutination is promoted.

Neutralization of Viruses

It is the process in which complement enzymes and some other components of the complement cascade attack and disturb some virus structures. In this way, viruses are rendered nonvirulent, and they become inactive. Such viruses cannot cause any disease.

Chemotaxis

Some of the products of the complement system cause chemotaxis of neutrophils and macrophages. They cause the migration of white blood cells to the tissue spaces that are adjacent to the areas invaded by foreign antigen.

Activation of Mast cells and Basophils

Some components of the complement system cause activation of mast cells and basophils. These cells release histamine, heparin, and other substances into the local tissues spaces. This results in increased blood flow as well as leakage of plasma and proteins into the local tissues spaces. They also cause local tissues reaction to immobilize the antigen at its entry site and prevent its further spread.

Inflammatory Effects

Some products of the complement cascade have other inflammatory effects like increased capillary leakage of plasma proteins, increased local blood flow and coagulation of proteins in interstitial fluid.

Classes of Antibodies

Antibodies are classified into five general classes. Each class has some special characteristics that are not found in antibodies belonging to others. The five general classes include IgM, IgG, IgD, IgE and IgA. Ig here stands for immunoglobulins. The respective letters represent the class being discussed.

A brief detail of each of these classes is mentioned below.

IgG

It is the most abundant antibody found in humans. It accounts for more than 75% of total immunoglobulins found in the blood. It is a monomer of a divalent structure. This means that IgG has two heavy chains and two light chains. It exists in the form of a monomer.

IgG is the only antibody that can cross the placenta. It means that maternal IgG can enter the fetal blood and provide immunity even in the absence of an antigen.

The levels of IgG rise during the secondary response that occurs after the second exposure of antigen. It provides long term immunity against the specific antigen.

IgM

IgM antibody exists in the form of monomer or pentamer. In the pentameric form, five antibodies are attached together via a specific protein called J protein. The polymeric IgM have ten binding sites and provides an effective mechanism to protect the body from the invading antigen.

Unlike IgG, the levels of IgM rise during the primary response that takes place immediately after the first exposure of antigen.

IgM cannot cross the placenta. It also has antigen receptors on B cells.

IgA

It is the second most abundant antibody found in normal individuals. This antibody can exist in monomeric or dimeric form. The J protein is present in the dimeric IgA.

IgA is mostly present in the secretions of the body. It causes the opsonization of the foreign particles. It prevents the attachment of viruses and bacteria to the mucus membranes.

IgD

This antibody exists only in monomeric form. It is found on the surface of B cells, where it acts as a receptor for antigens. The rest of the action of this antibody are insignificant.

IgE

It is an important antibody in hypersensitivity and allergic reactions. It is present on the surface of mast cells and basophils, where it acts as a receptor for specific allergen (antigen). Upon exposure to the respective allergen, IgE causes the release of mediators from basophils and mast cells.

IgE is also present on eosinophils. Here it causes the release of enzymes from eosinophils that provide protection against worm infections. IgE is the main defence mechanisms of the body against parasitic infections.

Vaccination

Vaccination is a process of creating immunity in a population against a specific by inoculating them with a vaccine. Vaccination has helped reduce the prevalence of a number of fatal diseases to a very low rate. Some diseases have been eradicated from the globe by an extensive vaccination process. Currently, the covid vaccine is being used worldwide to control the pandemic of the coronavirus.

Once a vaccine has been introduced in the body of an individual, it takes some time to provide immunity against that specific disease. Vaccines may have some side effects and can also produce mild symptoms of a specific disease.

All vaccines do not act in the same way. Different vaccines have different modes of action based on the nature of the vaccine.

Types of Vaccines

As mentioned earlier, all vaccines do not have a similar mechanism of action. Based on the process by which antibodies provide immunity, they are divided into the following categories.

Live Attenuated Vaccine

In these vaccines, alive organisms are used to produce immunity in the host against that pathogen. The organism used in the vaccine is harmless as they have been attenuated. The pathogenicity of these organism has been destroyed. However, they have antigenic surfaces as well as the ability to multiply within the host.

The antigen present on the surface of these attenuated organisms promote the production of antibodies against the specific organism. The antibodies thus produced remain in the blood of the host throughout life.

If the same pathogen enters the body after the person has been immunized, the already present antibodies will recognize it and initiate an immediate response. The harmful pathogen will be removed before it can produce disease.

Example of live attenuated vaccines are the BCG vaccine, oral Polio vaccine, the vaccine for measles and mumps.

Killed or Inactivated Vaccine

In these vaccines, the organism has been killed by a different mechanism like heat, formalization by chemicals, etc. However, the antigenicity of the organism is still preserved. The antigens present on the surface of the pathogens cause production of antibodies against them. These antibodies will provide protection against this organism upon second exposure.

These vaccines are generally safe as compared to live attenuated vaccine.

Examples of killed vaccine are Typhoid, Pertussis, Cholera, Hepatitis B, etc.

Toxoids

These vaccines are prepared from the exotoxins produced by some pathogens. The exotoxin is extracted from the organism and is neutralized to reduce its toxicity. However, the antigenicity of the toxin is maintained during the entire process.

The toxoids induce the production of antibodies directed against that specific toxin. These antibodies do not act directly on the invading organism. Rather, they bind the exotoxin and neutralize its effect.

Examples of toxoid vaccines are tetanus and diphtheria vaccine.

Combinations

As the name indicated, if two or more types of immunizing agents are mixed together to form a vaccine, it is called a combination vaccine. Today, combination vaccines are largely in use throughout the world.

Examples of combination vaccines are the DPT vaccine, DT vaccine, and MMR vaccine.

Polyvalent Vaccine

If a vaccine is prepared from two or more strains of the same species, it is called a polyvalent vaccine. These vaccines provide coverage against different strains of the same organisms.

Examples of polyvalent vaccines are the polio vaccine and influenza vaccine.

Summary

  • Antibodies are plasma proteins that provide immunity against specific organisms by recognizing them and initiating an immune response. They do so by recognizing and binding to the specific antigen.
  • Antibodies are produced and released into the blood by plasma cells. These cells are produced by B lymphocytes. B lymphocytes undergo preprocessing in the liver and bone marrow and are later moved to the lymphoid tissues. Here, they form different clones upon exposure to an antigen. Re-exposure of the antigen causes the B lymphocytes to form lymphoblast, some of which differentiate to form plasmablasts and give rise to plasma cells.
  • Antibodies have a divalent structure consisting of two light chains and two heavy chains. Each chain has a constant portion and a variable portion. Antigen binds to the variable portion of an antibody.
  • Antibodies can perform their action either by direct method or indirect method. In the direct method, they directly act on the foreign organism, while in the indirect method, they perform their action by activating the complement system.
  • Antibodies are divided into five major classes.
  • IgG is the most abundant one that can cross the placenta.
  • IgM is raised in primary response and has a pentavalent structure.
  • IgA is found in secretion on the mucosal surfaces.
  • IgD is found as a receptor on B cells.
  • IgE mediates allergic reactions in the body.
  • Vaccination is a process that induces the body to produce antibodies without developing the disease. Vaccines have a different mechanism of action based on their nature, as described earlier.

References

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  4. Borghesi L, Milcarek C (2006). “From B cell to plasma cell: regulation of V(D)J recombination and antibody secretion”. Immunologic Research. 36 (1–3): 27–32. doi:10.1385/IR:36:1:27. PMID 17337763. S2CID 27041937.
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