Antigen: Structure, Types and Factors Affecting Immunogenicity

The substance that induce a specific immune response and subsequently react with the products of a specific immune response is called antigen (it is more appropriately called as immunogen).

In the case of infectious diseases, the antigens are components of invading microorganism’s structure that are usually composed of proteins or polysaccharides.

Ag has to be recognized by the

Among the biological macromolecules, protein is the most potent immunogen followed by the polysaccharide. Other macromolecules such as lipids and nucleic acids do not serve as immunogen.


For Cell Mediated immunity only proteins and some lipids/glycolipids serve as immunogen.

Properties of an Immunogen

Immunogenicity: Ability to induce a humoral and/or cell mediated immune response.

Antigenicity: The ability to combine/react specifically with the final products of the above responses (i.e., antibodies and/or cell-surface receptors).

All molecules that have the property of immunogenicity also have the property of antigenicity but Reverse not true. Remember: All Immunogen are Antigen but all Antigen are not Immunogen e.g. Hapten.

Hapten are antigenic but incapable by themselves of inducing a specific immune response, i.e., they lack immunogenicity




The substances that are least immunogenic are

a) Proteins

b) Polysaccharides

c) Nucleic acids

d) None of the above

Factors influencing Immunogenicity

Nature of the Immunogen

  1. Foreignness
  2. Molecular size
  3. Chemical composition and heterogeneity
  4. Ability to be  processed and presented with an MHC molecule on the surface of APC or altered self-cell

Biological system that the antigen encounters

  1. Genotype of the recipient animal
  2. Dosage and route of administration

Factors influencing Immunogenicity

Ⅰ. Foreignness

Must be recognized as non-self by the biological system

Degree of immunogenicity depends on the degree of foreignness    i.e. The greater the phylogenetic distances between two species, the greater the structural (and therefore the antigenic) disparity between them.

e.g. If Bovine serum albumin is injected in Cow, Rabbit and Chicken, the order of Immunogenicity will be:

        Cow < Rabbit < Chicken (least for cow and most for chicken)

This property is govern by: Tolerance to self (specific unresponsiveness to self antigens)

Concept of tolerance

During lymphocyte development immature lymphocyte are exposed to self-components.

  1. Those that reacts with self antigen are killed (clonal deletion)
  2. Antigens that have not been exposed to immature lymphocytes during this critical period may be later recognized as nonself, or foreign, by the immune system.

Exceptions: Conserved macromolecules across species (e.g. Collagen, Cytochrome C:  no immunogenicity)

Remember: Sequestered Antigen are treated as foreign (eg. Corneal tissue, sperms) e.g. aspermatogenesis


Ⅱ.  Molecular Size

Correlation  exists between size of the macromolecule and its immunogenicity

1.Molecular Mass  ≥ 1,00,000 Da:  Active Immunogens
2. Molecular Mass 5000-10,000 Da: Poor immunogen

Exceptions: Few substances with molecular mass less than 1000 Da have proven to be immunogenic.

III. Chemical Composition and Heterogeneity

Susceptibility to Ag Processing and Presentation

Contribution of the Biological System

1.Age: Usually the very young and the very old have a diminished ability to mount an immune response in response to an immunogen.

2.Genotype of the recipient animal:

Immunogen Dosage and Route of Administration

A: Amount of Immunogen 

B: Times

Primary Vs. Secondary Immune Response

C. Routes of Administration:

e.g. intravenous  (spleen); subcutaneous (local lymph nodes)

Use of Antigen with or without Adjuvants


Freund’s Adjuvant

Main disadvantage: it can cause granulomas, inflammation at the inoculation site and lesions.


Freund’s incomplete adjuvant

Freund’s complete adjuvant

Types of antigens

T Dependent Antigen (Td-Ag)

T Independent Antigen (Ti-Ag)

Super Antigen (SAg)

Examples of superantigens include:


Heterophilic Antigen

1.An antigen that is possessed by a variety of different phylogenetically unrelated species. Antibodies induced by these antigens cross-react with individual heterophilic antigens.
This antigen type is involved in the pathogenesis of certain diseases, e.g. infectious mononucleosis, rheumatic fever, glomerulonephritis.

e.g. Antigen of Group A beta hemolytic streptococci (Streptococcus pyogenes) and antigens of the human myocardium are heterophilic

Examples of Heterophile antigens

Antigen in disease Diagnosis


Paul-Bunnell test is based on sharing of antigens between: