Immunology and Immunotechnology

Prof. C. Kameswara Rao
(All terms in bold are defined, either at the first mention or in groups of related terms)

INTRODUCTION

In ancient China and India, there was an effective, though highly dangerous, practice of introducing the fluid from the pustules of small pox (variola, variolae) patientsinto healthy individuals, through dermal incisions.   This practice, called variolation, using live smallpox virus, was aimed at protecting the individual from contracting the disease.

In 1796, Edward Jenner, the English Physician, obtained the pus from the pustules of a dairymaid suffering from cowpox and introduced it, through a nick made in the arm, into the system of an eight-year-old boy and demonstrated that it gave the boy immunity against smallpox.   This has opened up a new area in medicine, immunology.      

Immunology is sometimes called serology, as the principal participants of immunological reactions reside in the blood serum, although, strictly speaking, serology is the study of the serum, and the properties and functions of its components.

Rooted in the Latin word vacca for cow, the introduced substance is called the vaccine and the process vaccination.     Vaccination imparts immunity (protection) against the disease, and so, the individual is immunised.

Under the current practices, a killed or attenuated (made less potent) pathogenic organism (viruses, bacteria) or its biological product such as a protein, such as the cholera or tetanus toxin (the inoculum) is introduced into a living being.   This process is inoculation.   In practice, the terms vaccine and inoculum, are virtually synonymous and so are vaccination and inoculation. 

Over the time, immunology has absorbed to an immense benefit, from advances in human physiology, medicine, biochemistry, molecular biology (particularly protein structure and chemistry), and a range of electronic instrumentation including computers.   Today, immunology is a very complex and sophisticated area of biology, which has become one of the most versatile research tools in biology and medicine, as well as a powerful weapon in the armoury of prevention and management of several viral and bacterial diseases.   The significance of immunology in human is amply reflected by the large number of Nobel Prizes awarded to research in this area.   These award winning discoveries (Table) represent the mile stones in the development of modern immunology, and constitute more than 10 per cent of all Nobel awards for Physiology or Medicine, since 1901.

Table

Nobel Prizes awarded for discoveries in immunology or related areas

Immunology helped us to eradicate smallpox.   It has saved millions from polio, cholera, hepatitis, tetanus, rabies, and several other potentially debilitating or fatal diseases.   It is the hope of mankind, to prevent many other diseases such as malaria, tuberculosis, and even certain types of cancer, through appropriate vaccines.      

Immunotechnology, is an important arm of biotechnology, constituting the industrial scale application of immunological procedures to produce vaccines, for mass immunisation to prevent prevalent diseases and/or producing immunological therapeutic agents to cure the afflicted.    Production of protein vaccines has been in large-scale use for a long time and the current trend is to develop the more specific DNA vaccines.

IMMUNOLOGICAL DEFENSIVE RESPONSE

When an infecting organism gains entry into the mammalian system for the first time, the immune system of the mammal reacts, mainly in response to the proteins of the invading organism, generally called antigens, by producing a special class of proteins called antibodies.    This first encounter is very important because the system gains a ‘memory’ template of the three dimensional structural configuration of the epitopes of the antigens.   This memory may last for a few hours or days (common colds), a few months (cholera, tetanus) or the lifetime (smallpox) of the individual. 

Antigens, the molecules that trigger antibody response, fall into three categories, called antigens, immunogens or haptens, which are sourced in the protein coats of viruses, cell walls of bacteria, secretions of pathogenic organisms, proteins from plant or animal parts that were injected, ingested or inhaled, or introduced into the system by some means.

When the same antigen gains entry a second and the subsequent times, the immune system recognises the foreign entity and produces antibodies specific to the antigen, basing on the memory, developed on the first encounter.   This is immune response, which results in  a) the production of antibodies, b) antibody-bearing cells or  c) cell mediated hypersensitivity reaction (allergy).

Each re-entry of the exogenous entities triggers enhanced production of the corresponding antibodies (booster reaction).  

The antibodies recognise their antigens, bind with them, and neutralise them, before they can cause harm to the individual or cause the disease specific to them.   This is immunological defence. 

The antigen-antibody recognition is a highly specific phenomenon of biorecognition at the molecular level.   Such a high degree of specificity is also found between the enzymes and their substrates, and  lectins and their specific carbohydrates.  

Immune response is a selective reaction of a mammalian body to substances that are foreign (exogenous) to it or those that the immune system identifies as foreign.   The three important aspects are:

a)      Memory: the primary response of the formation of the memory template at the first
         encounter,

b)      Distinction between self- and non-self:  distinction between the organism’s endogenous
         proteins and those that are foreign (exogenous), and 

Other animals and even plants have defence mechanisms against diseases, but they are not identical to the mammalian immunological defences.   For this reason, immunology is a mammal centred area of biology.     Mice, rats, rabbits, dogs, horses and monkeys have been instrumental in the advancement of the field of immunology.

Mammalian systems produce a highly specific antibody to each of the pathogens and even their different strains.  The antibody recognises the antigen and binds with it forming an antigen-antibody complex, and neutralise the pathogen’s potential to cause the disease.      The antigen-antibody complex is scavenged by the body, mainly through the lymphatic system and often seen as pus, in dermal eruptions in the form of pustules.   Pus, the fluid from pustules, contains serum, antigen-antibody complexes, expended white blood cells, dead and live pathogens, and debris of tissue.  

COMPONENTS OF THE IMMUNOLOGICAL SYSTEM AND THEIR ROLE

A large number of complex and interconnected components operate in the immune system.   Understanding the role each one of them is essential to manipulating the system to our advantage.

THE FLUID COMPONENTS

Serum:  The liquid part of blood, without the cells and the coagulating factors, but containing antigens and antibodies; it is the storehouse and means of transport of immunological components.

Lymphatic system: is parallel to the blood conducting system and is constituted of the lymph, lymphocytes, lymph vessels, lymph nodes and lymph glands.   The lymph is a watery, transparent or slightly yellow, fluid conducted through the lymph vessels.  Lymph contains only one kind of cells, the lymphocytes, unlike blood that contains several different kinds of cells   including lymphocytes.  The blood and the lymphatic systems come into a sort of confluence in the lymph nodes and the tissues.   The lymph cells that secrete lymph are aggregated into lymphatic   tissue in the form of glands or occur in small groups of cells in different parts of the body.

THE CELLS AND TISSUES

Haemopoiesis (haematopoiesis):  The formation of the cellular components of blood, originating very early in the yolk sac of the egg.  In the foetus the liver performs this function and later the bone marrow takes it over and continues throughout life.   Haemopoiesis originates with the stem cells in the bone marrow.

Stem cells:  Stem cells are the basic cell type with potential to develop different cell components of the mammalian body system.   Stem cells from the foetus are totipotent and can form almost any organ.   The stem cells from the bone marrow are multipotent and form the cellular elements of both the blood and lymphatic systems in addition to the formation of new stem cells.   The stem cells migrate to the thymus and differentiate into T-lymphocytes, in   the microenvironment of the thymus.  

Erythrocytes:  The enucleate discoid cells in the blood with membrane bound haemoglobin, to which oxygen binds reversibly (red blood corpuscles).    Erythrocytes bear antigens on their surfaces that are responsible for the human blood groups in the ABO system.   Blood group antigens also circulate in the blood and hence are responsible for the rejection of transplanted tissues/organs.

Leucocytes:      All the different kinds of cells in the blood (the so-called white blood corpuscles), including the lymphocytes, but with the exception of the erythrocytes.  

Lymphatic tissue/cells:  As explained above, the lymphatic system is also composed of cells and tissue.

Lymphocytes:   The cells of the lymphatic system (lymphoid group) which play the main role in immune responses. 

Role of lymphocytes: The lymphocytes have an important role to play both in humoural and cell-mediated immunity.  The lymphocytes re-circulate in the blood, lymph nodes, spleen and other tissues and back to blood by the lymphatic vessels.

When rats were depleted of lymphocytes, their ability to show the primary response to antigens or to reject skin grafts was very much impaired.   Immunological responses were restored in these rats when lymphocytes from another rat were injected.  This adequately shows the importance of lymphocytes in mounting immune response.

Kinds of lymphocytes:

a) T-lymphocytes, of four subclasses and the B-lymphocytes (T-cells and B-cells) basing on origin, and 

b) Three kinds of lymphocytes, large, medium and small, basing on size.  

When lymphocytes are incubated at 37°C for 24 h, the large and   medium lymphocytes are killed.    The remaining   small lymphocytes can restore immune responses when injected into rats that were previously drained of lymphocytes.

The small lymphocytes are necessary for the primary response to an antigen and they can become 

a)      Antibody synthesising cells called plasma cells, or 

b)      Effector cells called lymphoblasts. 

The lymphoblasts, along with blood group antigens, are responsible for immunological tissue rejection reactions in transplantations.  The small lymphocytes also carry the memory of the first contact with an antigen.   Without this memory mechanism, there can be no secondary response and so no immunological defence.

Hybridoma:  A synthetic cell line (such a myeloma cell and a spleen cell) that can grow in a culture indefinitely, at the same time producing antibodies.

Thymus:  A gland lying behind the breastbone and extending up to the thyroid gland.  The thymus is well developed in the infancy (about 40 g) and reaches its greatest size at about puberty (100 to 120 g) but is reduced by about 50 years of age  (about 20 g), as it is progressively replaced by fatty tissue.   

So long as it is occurring, the thymus mediates the differentiation of the T-lymphocytes, which are concerned mostly with cell-mediated immunity.

When the thymus was removed from mice at birth, they showed a decrease in lymphocyte count, their ability to reject tissue grafts was severely affected, their humoural antibody response was restricted and they soon died.   When mice without the thymus were grown under germ free conditions, they survived showing that the ability to fight infection was impaired due to the removal of the thymus.

When mice were subjected to x-rays, their lymphocytes failed to multiply.   When these mice were injected with bone marrow cells, their lymphocyte count normalised but not in mice without the thymus.   These studies emphasise that the bone marrow cells develop into lymphocytes and that the thymus is necessary for this process.

Children with abnormalities of the thymus suffer from immunological disorders.

Bursa of Fabricius:  In birds, there is a recognisable lymphoid organ called the Bursa of Fabricius, which is similar in structure to the thymus.   The Bursa is responsible for the production of B-lymphocytes that are involved in the humoural immunity.   

When the Bursa was removed, chicken failed in humoural antibody synthesis but not in cell-mediated responses.

The lymphocytes that differentiate in the microenvironment of the Bursa are different from the T-lymphocytes and so are known as the B-lymphocytes.   In man and other mammals, the bursa or its equivalent has not yet been identified.  However, foetal liver and bone marrow cultures provided adequate evidence to consider that the    B-lymphocytes    in   mammals   differentiate    in    the microenvironment of the blood cell producing haemopoietic tissue of the bone marrow. 

Distinguishing T- and B-cells: It is very difficult to distinguish between the T- and B-lymphocytes using a light microscope or even an   electron microscope but certain tests ensure this.   One of the common methods used to recognise human T-cells is to mix them with the red blood corpuscles of sheep when the two kinds of cells form rosettes   (formations resembling roses).    The B-cells   are recognised by using fluorescent dyes along with anti-immunoglobulins   (antithetic antibodies).

Modified T- and B-cells: The populations of both the T- and B-cells are stimulated to proliferate and undergo morphological changes by antigens.   The T-cells become lymphoblasts and participate in cell-mediate reactions.   The B-cells become the plasma cells participating in the humoural antibody synthesis.  There is co-operation between the two populations of lymphocytes.  The mature plasma cell actively synthesises and secretes the antibody.    There are no antibodies in, or secreted by, the T-lymphocytes.     

T-cell dependence of B-lymphocytes:  Certain of the B-lymphocytes in mammals are dependent upon the T-lymphocytes for their function (T-cell dependent) while the others are independent of the T-lymphocytes (T-cell independent).

Monocytes, macrophages and phagocytes:  Monocytes, originate from stem cells, have a   single nucleus and develop into   macrophages--the phagocytic   cells, which engulf particulate matter, in a non-specific defence mechanism.    

Mast cells:  Mast cells occur in the skin and epithelial layers.   They contain histamine in the form of granules bound to membranes.   Explosive de-granulation results in the release of histamine, which increases the permeability of the blood vessels, causing inflammatory reactions.   Mast cells have a key role in allergy.

Eosinophils:  These are cells with granules in the cytoplasm (one kind of granulocytes), also known as polymorphonuclear leucocytes, stainable with the reddish biological stain eosine.    The mast cells and eosinophils have an important role in allergy.  

THE MOLECULES

Antigen: a substance, usually a protein, that stimulates the immune system to produce a set of specific antibodies and that combines with an antibody specific to itself, at a specific binding site; differs from immunogen in that it is not involved in eliciting cellular response and in that it can complex with antibodies.  

Immunogen:  a substance, usually a protein, that elicits a cellular immune response, and/or antibody production; differs from antigen in that it mainly elicits cellular response but does not complex with an antibody.

Hapten: a low-molecular weight non-protein molecule which contains an antigenic determinant but which is not itself antigenic unless it complexes with an antigenic carrier, such as a protein; once an antibody is available, it can readily recognise the hapten, even without the carrier, and bind with it.   To be antigenic, the hapten must bind to an exogenous protein carrier.   

Epitope:  a part of a protein molecule that acts as an immunogenic/antigenic determinant, and so determines specificities; a macromolecule, such as a protein, may contain many different epitopes, each capable of stimulating the production of specific antibodies, each with a correspondingly specific binding site.

Antibodies:  Globulin (roughly spherical in shape and extractable in saline solutions) glycoproteins (proteins with a carbohydrate content ranging from 3 to 13%), produced by the immune system of an organism in response to exposure to a foreign molecule and characterised by its specific binding to a site, related to an epitope of that molecule; induced response proteins.

The antibodies, like all proteins, are formed of chains of amino acids, which undergo very complex packing, giving the proteins a specific and functionally significant final shape (tertiary configuration), which determines most of the characteristics of the protein.  

As globulin proteins are involved   in   immune reactions, antibodies are   called immunoglobulins (abbreviated to Ig).  

Antiserum:  Blood serum containing antibodies arising out of immunisation or after an infectious disease.

Production of antibodies: Antibodies are produced by the lymphocytes.   The process of antibody production and immune response are complex and both the lymphatic and the blood systems are very closely involved.

Autoantibodies:  In certain pathological conditions, the thymus may produce antibodies to the body’s own endogenous proteins (auto-antibodies), which complicates the immune system.

Antithetic antibodies:  Antibodies produced against antibodies; antithetic antibodies have properties similar to those of the antigens.

Polyclonal antibodies: antibodies produced by molecules with several different antigenic determinants (epitopes) and/or several different cell populations.

Monoclonal antibodies: antibodies produced against a single antigenic determinant (epitope) and/or by a single cell population; hence are very specific.

THE IMMUNOGLOBULINS

Immunoglobulin (Ig):  A protein molecule of the globulin-type, found in the serum or other body fluids and that possess antibody activity; there are five classes of immunoglobulins (IgA, IgD, IgE, IgG and IgM), based on antigenic and structural differences.    In addition to these five classes, there are several subclasses  (four in IgG) and other variants of Ig molecules.

Classes of antibodies: There are five classes of immunoglobulins in the human system:  Immunoglobulin G (the gammaglobulins; IgG), IgA,  IgM,  IgD and IgE.

Molecular structure of the antibodies:  The conventional model of the Ig molecules is a ‘Y’ shaped configuration, with two heavy chains and two light chains, with two open arms containing the antigen combining sites, which occur on both the light and the heavy chains.   The two heavy chains are bound together by disulphide bonds.   At any point, the molecule has two chain sections, parallel to each other.  

The modern view of the structure of the Ig molecules is to look at them as containing series of regions activity called domains.  Variable light, variable heavy, constant heavy 1,2,3 and constant light are the domains recognised on Ig molecules.   The constant domains provide for the identity of the molecules and the variable regions are responsible for the diversity in the specificity of the antibodies.

Ig molecules may occur as monomers (IgG and IgA), dimers (IgA) or pentamers (IgM) (Igfig. 4).   Linking monomers by J chains forms higher configurations. 

Immunoglobulin A (IgA):  With a molecular weight of about 1,60,000, IgA molecules are only slightly heavier than the IgG molecules but they can form aggregates of higher molecular weights.   IgA are about 13% of the total Ig with a concentration of 1.4 to 4 mg/ml in the normal serum.   The IgA are the major Ig in the serum and mucous secretions, such as saliva, tears, nasal fluids, sweat, lung and the gastrointestinal tract.  They defend the exposed external surfaces of the body against the attack of microorganisms.   IgA antibodies seem to inhibit adherence   of the microorganisms to the surface of the mucosal cells and thus prevent their entry into the body tissues.   IgA molecules differ from the other Ig classes in having three disulphide bonds holding the two heavy chains, instead of two bonds in the others. 

Immunoglobulin M (IgM): The IgM molecules are the heaviest of all Ig.   They have a molecular weight of 900,000 and so are often known as the macroglobulins.   They form about 6% of the total Ig and occur in a concentration of 0.5 to 2% of the normal serum.   IgM are very efficient agglutinators of bacterial cells and are   effective cytolytic agents.   They form the most immediate and effective first line defence against bacteraemia.   Since they appear in response to infection they are mostly confined to the blood stream.   The anti-A and anti-B haemagglutinins and many antimicrobial antibodies as well as typoid exotoxin   antibodies are all IgM.   During the course of evolution of Ig,  IgM seem to have appeared earliest.

Immunoglobulin G (IgG): IgG molecules are the lightest of all the Ig and have a molecular weight of about 1,50,000 and about 3% carbohydrate content.   They form about 80% of the total Ig of the human body.  In the normal serum their concentration ranges from 8 to 16 mg/ml.   These are the most abundant component of Ig in the body fluids particularly the blood vessels where they combat microorganisms and their toxins.   IgG are the only antibody that can get across the placenta and so provide the major line of defence during the first few weeks of the life of a foetus.    IgG also diffuse very readily from the blood vessels into the body spaces.   When IgG molecules attach to microorganisms, the susceptibility of the   latter for phagocytosis increases.    In a germ   free environment, the IgG concentration of the serum is very low and increases   with infection.    IgG are the   major    antibody synthesised during the secondary response, their synthesis being entirely governed by the antigenic situation.

All the IgG molecules are seemingly identical.   The most fascinating thing is that there are an infinitesimal number of antigens, with each pathogenic organism producing several of them.   During the course of our lifetime we develop immunity against a very large number of infections, some on a long-term basis and some ephemeral but repeated infection renewing our ability to combat the disease.   The key to understanding this versatility of the IgG molecule lies in the fact that the IgG molecule has a part that is invariable and this gives the basic characteristics for it to function as an antibody.  Another part of the IgG molecule is variable in its amino acid content and sequence and this gives the molecule the ability to be a specific antibody against a particular antigen.   This is nothing surprising.   Almost all proteins have variable and invariable regions.

Immunoglobulin E (IgE): The molecular weight of IgE is about 200,000 and they form only 0.002% of the total Ig with a serum concentration of 17 to 450 ng/ml.   IgE protect the external mucosal surfaces of the body through plasma factors.   Pathogens crossing the IgA line combine with IgE molecules specific to them.  This results in the release of amines (eg. histamine) that increase the permeability of the blood vessels causing the symptoms of allergy.   The release of amines is due to a degranulation of the mast cells.  The level of IgE is raised during parasitic infections but the importance of IgE lies with atopic allergy.

Immunoglobulin D (IgD):  IgD have a molecular weight of about 1,85,000 and form only about 1% of the total Ig.   They occur at a concentration of 0  to  0.4% of the normal serum.   They are present only on the surface of the lymphocytes along with IgM.    The IgD are susceptible to enzyme degradation and so have a very short life span (2.8 days) in the plasma.  IgD have the highest carbohydrate content (13%) of all Ig.   The exact function of IgD is not understood.

TYPES OF IMMUNOLOGICAL REACTIONS

Agglutination:  an immunological or chemical reaction leading to the aggregation of particulate matter such as bacteria, erythrocytes or other cells, or synthetic particles such as plastic beads coated with antigens or antibodies.

Precipitin reaction: When an antigen and its antibody are brought together in solution, a precipitate is formed due to the binding of the antigen and the antibody.   If unrelated antigen and antibody are brought together no binding occurs and hence no precipitate is formed.  Antigen-antibody binding occurs when they come   together   in the blood stream or in   the   tissues.  Precipitation occurs because the antigen-antibody complexes form a three-dimensional lattice.   Precipitin reactions are a very useful tool in several areas of biological research.

In the case of both antigen-antibody and enzyme-substrate affinity, there is a complementarity of the molecular shape between the antigen/enzyme and the antibody/substrate and the fit is exact like that of a key in its lock.

In semisolid media, such as bacto agar, the precipitin reaction results in the formation of lines called precipitin lines.   Such reactions are studied by Ouchterlony’s double diffusion method, where the antigen and the antibody diffuse towards each other from two spaced wells cut in semisolid agar.   This method provides only qualitative data.   A variant of this method is single radial diffusion, which helps to quantify the antigen with reference to the antibody.   

Basis of recognition of the antigen by the antibody and their binding:  The overall physical configuration of the antigen seems to be more important than its chemical structure which means that the antigen is recognised by the three-dimensional shape of its outer electron cloud.  Chemical composition and reactivity are less important.

Binding site: a specific region in a molecular entity, such as an antigen, that is capable of entering into a stabilising interaction with another molecular entity, such as the corresponding antibodies.

Forces of antigen-antibody binding: One or more of the following forces appear to be involved in antigen-antibody binding: electrostatic forces, hydrogen bonding, hydrophobic (water repulsion) forces and Van der Waals attractions   between molecules.   What is surprising is that the very same forces also operate between unrelated proteins or other macromolecules in normal chemical reactions.

TYPES OF IMMUNITY

Humoural immunity:  When   microorganisms   enter the body, antibodies   are synthesised and released into the blood and other body fluids.  These antibodies circulate throughout the body.    The free antibodies coat the cells of the organism and enhance their phagocytosis and also neutralise the toxins released by the organisms.   This type of immune response is called the humoural immunity.

Cell-mediated immunity:  In response to the presence of antigens, the body produces lymphocytes with antibodies or antibody-like molecules on their surface.  This is cell-mediate immunity, which offers protection, particularly against organisms, which live and multiply within the host cells.   Tubercle bacteria, small poxvirus, etc., are subject to the action by cell-bound antibodies.

Acquired immunity: Not all antibodies are synthesised in the body.   Some are pre-natal acquisitions from the mother through the placenta and some are post-natal through breast-feeding.   These constitute acquired immunity.    Immunity is also acquired through one’s own body’s experience gained on encountering a pathogen.  

Specific and non-specific defence:  Immunological defence is specific to particular pathogens, and even to their strains.   This is specific defence.   Mammals have also a non-specific defence mechanism.   For example, the macrophages, that are associated with the lumenal side of the walls of the blood vessels and the connective tissue, physically engulf cells of pathogens or complexes of proteins, to remove them from the system.

BODY’S IMMUNOLOGICAL REACTION

Allergy: A hypersensitivity reaction of the body to antigens.   In a sense it is the immunological system that has gone wrong.   An allergen is an antigen that stimulates the production of IgE antibodies, although low titres of IgG molecules are also formed.   The IgE antibodies bind to mast cells resulting in the ‘explosion’ of the mast cells leading to the release of histamine that triggers an inflammatory response in the skin, mucosa or epithelial cells, a syndrome termed allergy.

Allergen: an antigen that can induce an allergic reaction, thorough eliciting IgE antibodies.   Some allergens are haptens, as for example parthenin which is a sesquiterpene lactone.    Some haptens bind to endogenous proteins in the individual, because of which IgG antibodies cannot be produced against such a hapten-carrier complex, a situation that makes it almost impossible to treat the patient through immunisation. 

Anaphylaxis:  a sudden and severe form of IgE based reaction, occurring on the second encounter with the allergen (antigen) that can be fatal.   Penicillin may induce a severe anaphylactic reaction in some individuals sensitive to it.  In fact, purified or synthetic penicillin does not cause anaphylaxis, but the impurities in biologically produced penicillin or protein compounds such as procain added to penicillin injection, are responsible for the reaction.

Inflammatory response: This is the body’s reaction to injury or infection/antigens, in the form of a syndrome constituted of swelling, redness (erythema) and heat (collectively called inflammation), in the affected part of the body.   Inflammation controls the spread of infection.   Uncontrolled inflammation causes tissue damage.

INHIBITION OF IMMUNE RESPONSE

Antigen-antibody completing, phagocytosis, inflammation during immune response, etc., all lead to tissue damage.   Uncontrolled immune reactions can be dangerous to us.   There are some factors that inhibit immune response and some situations where immune responses fail to materialise.

a) Antibody suppressor cells and/or factors are present in our serum or tissues.   Prostaglandins, the compounds secreted by the organs of the human body into the blood stream to perform various functions, such as muscle contraction, may also inhibit immune reactions.    This is the body’s way of controlling immune reactions to minimise tissue damage.

b) While our body prepares for extensive warfare, the pathogens   themselves   would not be idle.    A   number   of immunosuppressive agents like lipopolysaccharides, lipoteichoic acid, dextran, Levan, etc., are produced by bacteria.  They also produce proteinases that denature some Ig classes, particularly IgA.   Modulation of immune responses both by the host and the pathogen ultimately regulates the host-pathogen interaction and the development of disease.

c) The antibodies can be defeated in their function by slight changes in the chemical  (and consequently physical) structure of the antigen.   This happens with the antigens of viruses and bacteria, which grow very rapidly and develop into new strains through mutations and other evolutionary processes depending upon several conditions, particularly environmental. Under   these conditions, the host’s immune defences   become inadequate.   For example, we never seem to acquire immunity from colds.   In fact, we do get immunised to a particular strain of cold causing virus of a given time but in no time the virus modifies itself in some minute way and we have no immediate defence against this modified version of the virus.   Antibody production against the ever-changing organisms is a race between the host and the pathogen.

SECRETORS AND NON-SECRETORS

All of us secrete antigens and antibodies in our body fluids such as sweat, tears, saliva, semen, etc., to some degree or the other.   For example, the IgA in saliva serves as the first line of defence of the oral route.   However, a certain percentage of human populations secrete antigens and antibodies in high titres and are called secretors, the other group being non-secretors.   The status of an individual as a secretor is genetically determined and offers certain advantages to the secretors in terms of body hygiene.   Their surface and first line defences are quite high compared to those of the non-secretors.   The frequency of secretor vs non-secretor alleles in different human populations is of interest to the population geneticist.   The status of an individual as a secretor (or non-secretor) is easily determined by the use of appropriate lectins, a class of proteins that can recognise and bind to cell surface carbohydrates, resulting in agglutination of cells, such as erythrocytes and lymphocytes.