Antigens (Ag): Meaning, Nature and Features | Immunology

In this article we will discuss about: 1. Meaning of Antigens 2. Nature of Antigens 3. Classification 4. Features 5. Factors.

Meaning of Antigens:

Classically, an antigen is defined as an orga­nism, a molecule, or part of a molecule or substance which may be self or non-self, can evoke noticeable immune response and can bound distinctively with antibodies. Antigenicity is the ability of antigen to combine speci­fically with the final products of immune system i.e., either with antibodies or with cell surface receptors.

Antigens, which are able to induce adaptive immunity, are called immunogens. All immuno­gens are antigens unless their ability to stimulate an immune response is significant.

Nature of Antigens:

Any foreign agent can act as an antigen, so antigen is of numerous type which is really end­less. Antigen may be a chemical substance like a protein or a polysaccharide. It may be a biological entity like, Bactria, bacterial products, fungi, para­sites, viruses, different microbes, or a larger para­sites.

Immune system can recognize any macro- molecules of an infectious agent, either proteins or polysaccharides. Proteins are recognized as a potent immunogens whereas polysaccharides are second in position. Sometimes lipids and nucleic acids may be treated as infectious agent when these are attached with proteins or polysaccha­rides.

Besides these, different biological products— milk, egg albumin, bee venom, snake venom, pollen grains may be a good source of antigen. Different parts of bacterial cells like flagella, pili, lipopolysaccharides of outer membrane of Gram- negative bacteria, the capsular polysaccharides of the cell membrane, cytoplasmic proteins, exotoxins, endotoxins etc. can have antigenic property and can evoke immune response against them.

Sometimes (normally very rare); self-protein can be recognized as non-self by body and can be treated as foreign substances against which body will take necessary steps to control the annomeles (called as auto-immune disease).

Classification of Antigens:

Antigens can be classified under two major categories, called:

(1) Exogenous and

(2) Endo­genous antigens.

1. Exogenous antigens:

Exogenous antigens are those antigens which enter within the host body from their surroun­dings or external environments. These are basically of pollutants, microorganisms, pollens, drugs etc. Different infectious diseases, are caused by these type of introduced or foreign external agents are normally called communicable diseases, e.g., influenza virus, malarial protozoa etc.

2. Endogenous antigens:

These types of antigens are located within the individual itself.

Endogenous antigens are again classified under three sub-categories named as:

i. Xeno-genic or Heterogenic antigens

ii. Allogenic or Idiotypic antigens

iii. Autologous antigens.

i. Xeno-genic antigens:

Xeno-genic antigens are those groups of foreign items which are related with tissue transplanta­tion and serology. Normally, these are called heterogenic antigens as they are related with phylogenetically unrelated species.

When a piece of tissue or graft is transplanted to an individual, it may be treated as foreign, then those molecules are considered as xeno-antigens. Similar foreign recognition may be resulted in serology. Cross-reactions are very common in between antisera to certain erythrocytic surface antigens or some bacterial antigens.

Antisera is formed against surface antigens. Produced anti­sera cross-react with cells or body fluids of animals belonging to different species due to presence of mucopolysaccharide and lipid based chemical determinants.

ii. Allogenic antigens:

Allogenic antigens are those antigens which are genetically determined, polymorphic in nature and help to differentiate one individual of one species from another individual belonging to the same species. When an individual (recipient) receives a blood transfusion or undergoes trans­plantation operation (like plastic surgery, kidney etc.)

These phenomena lead to incompatibility, agglutination and graft rejection. In case of human beings these types of anti­genic determinants are located on erythrocytes, leukocytes, platelets, cell surface markers, serum proteins and histocompatibility antigens.

iii. Autologous antigens:

This group of antigens is very rare and unnatural. In normal condition, self-components are non-immunogenic in nature, but in an abnor­mal condition self-body components are started to be considered as non-self or antigenic component.

Antigens can also be classified into two broad categories:

1. Comparison of T-independent and

2. T-dependent antigens.

Essential Features of Antigens:

There are two essential features found within the antigenic molecules:

1. The molecules must be recognized as foreign by the host.

2. After antigen processing, antigens must undergo some physical and chemical changes that can stimulate the immune system.

Factors that influence Immunogenicity (Antigenicity):

Immunogens play a pivotal role in deter­mining the status of immune system. Immune system always try to recognize foreign invaders and also try to get rid of antigenic effect.

Somehow, the body must recognize a foreign substance in order to evoke an immune response:

There are some essential factors which influ­ence the power of antigen (Fig. 4.1).  

Those are:

i. Molecular size,

ii. Structural stability,

iii. Degradability,

iv. Foreign­ness,

v. Chemical composition and heterogeneity,

vi. Antigen processing and presentation,

vii. Confor­mation and

viii. Accessibility.

i. Molecular size:

In general, large molecules are better antigens than small molecules. There is a direct correlation between the size of molecules and immunogenicity (Fig. 4.2 and Table 4.2).

As for example, hemocyanin is an inverte­brate blood protein with (6.7 x 10³)kDa molecular size, is a potent antigen in nature. Serum albumin from other mammals (69 kDa) is a fairly good anti­gen but may also provoke tolerance, whereas the hormone angiotensin (1031 Da) is a poor antigen.

Sometimes, very small molecules may bind to large proteins and resulting in formation of active antigen which can evoke an immune system. The best immunogens tend to have a molecular mass approaching 100000Da.

ii. Structural stability:

The recognition of a molecule or part of a molecule as foreign is possible by the cells of the immune system due to its specific shape. Those molecules are recognized as poor antigens which lack a specific or fixed shape. As for example gelatin is recognized as a poor protein due to its structural instability. This is being stabilized by cross-linking of the peptide chain with tyrosine or tryptophan.

The major protein of bacterial flagellum called flagellin is a weak antigen due to its unsta­ble structure; it is being enhanced by polymeriza­tion. Proteins are much more stable antigens than starch (polysaccharide), lipids, carbohydrates and nucleic-acids.

iii. Degradability:

Easy degradation of an antigenic molecule is considered as an important factor with respect to their antigenicity. The cells of the immune system recognize small molecular fragments and soluble antigens. When a molecule does not undergo breakdown process, it can not be considered as antigen.

For e.g., stainless steel pins and plastic joints are commonly implanted in the body with­out triggering an immune response. Different metals or organic polymers, plastic cannot be frag­mented and processed to form suitable for trig­gering an immune response.

Conversely, since immune responses are antigen driven, foreign molecules are very rapidly destroyed on entering the body may not provide sufficient stable antigen fragments to stimulate an immune response.

iv. Foreignness:

The first and foremost criteria for a molecule to function as an immunogen is that it must be or act as non-self to the host. The cells, whose func­tion is to respond to antigen (antigen-sensitive cells) are selected in such a way that they do not usually respond to normal body components.

The degree of immunogenicity depends upon the degree of foreignness of the immunogen. When an antigen is introduced into an organism, greater the phylogenetic distance between two species, the greater the genetic (i.e. antigenic) disparity between them. But all foreign substances do not elicit immune response.

As for e.g. carbon gra­nules evoke phagocytosis but not antibody pro­duction. But the bovine serum albumin (BSA) is an excellent immunogen when it is injected into a rabbit or other mammals but not at all an immunogen when it is introduced within the blood of cow itself.

A kidney graft from an identi­cal twin will be readily accepted but a graft from an unrelated human will be rejected in about two weeks and a graft from a chimpanzee to a human will be rejected within a few hours due to dispari­ty of protein structure and firmness with respect to evolutionary stand point view.

v. Chemical composition and heterogenity:

Not only molecular size, structural stability and foreignness but also chemical composition of an immunogen is an effective factor which affects its immunogenicity. As for e.g. artificial or syn­thetic homopolymers tend to lack immunogeni­city regardless of their size. Copolymers of suffi­cient size, containing two or more different amino acids are immunogenic.

The addition of aromatic amino acids, such as tyrosine or phenylalanine has immense effect on the immunogenicity of these synthetic polymer. As for e.g. a synthetic copolymer of glutamic acid and lysine requires a minimum molecular wt. of 30,000-40,000 for immunogenicity.

Besides chemical compositions, structural complexicity and heterogeneity of protein affect immunogenicity. Starting from nascent to final stage, proteins undergo four levels of organization called primary, secondary, tertiary and quarter- nary protein, which gradually add their structural complexity and impose effect on their immuno­genicity (Fig. 4.3).

vi. Antigen processing and presentation:

There is a great variety of antigens found within the body. Some antigens are readily be recognized by immune system (mainly by B-cells) and some require to be processed and presented in a presentable manner so that they can be recog­nized by immune cells (T-cells usually). There are intracellular (endogenous) and extracellular (exogenous) antigens which present different challenges to the immune system.

A foreign protein (antigen) to be recognized by a T-cell must be degraded into small antigenic peptides that form physical complex with Class I or Class II Major Histocompatibility Complex (MHC) molecules. This conversion of proteins into MHC associated peptide fragments is called antigen processing and presentation. This process­ing of antigens is mediated by different antigen cells of the body (Table 4.3).

Whether a particular antigen will be pro­cessed and presented together with Class I or Class II MHC, MHC is to be determined by which the antigen enters within a cell (Fig. 4.4).

Exogenous pathway (Cytosolic pathway):

Exogenous antigens are ingested by endocytosis or phagocytosis and then enter into the endocytic processing pathway. Antigen presenting cells (macrophages, dendritic cells, B-cells) degrade most of the ingested exogenous antigens into pep­tide fragments within the exogenous processing pathway.

Here, due to an acidic environment anti­gens are degraded into small peptides which then bind to the leaf within the Class II MHC molecules and MHC II bearing the peptide are then transpor­ted to the cell surface. The fragments of ingested antigens are presented with Class II MHC mole­cules on the membrane of antigen presenting cells.

T-cells displaying CD4⁺, recognize antigens asso­ciated with Class II MHC molecules and are thus said to be Class II MHC restricted. These cells are generally act as a T_H (T-Helper) cells (Fig. 4.5).

Endogenous pathway (Endocytic pathway):

Endogenous antigens are produced within the host cell itself (e.g., in a virus infected cell), is degraded within the cytoplasm into peptides which then move into the endoplasmic reticulum where they bind with Class I MHC molecules.

The peptide Class I MHC complexes then move to the surface of the cell via Golgi complex. T-cell displaying CD8⁺ recognize antigen associated with Class I MHC molecules and are thus said to be Class I MHC restricted. These cells are gene­rally act as Tc (T-Cytotoxic) cells (Fig. 4.5 and 4.6).

vii. Conformation:

Molecular conformation is another factor in determining the immunogenicity of a substance. Most of the substances having their particular conformation in which that can be specifically identified by specific antibody.

An effective anti­gen may turn into an ineffective one due to their changed or altered form as because recognition by an antibody is a very specific feature. An antigenic determinant is denoted by a particular stretch of amino acids derived from different parts of a folded polypeptide sequence.

viii. Accessibility:

An immune response is highly dependent upon the accessibility of determinant group to the recognition arm of the immune system.