Antigen and Factors Affecting Immunogenicity

The substance that induces a specific immune response and subsequently reacts with the products of specific immune response is called an antigen (it is more appropriately called an immunogen). In the case of infectious diseases, antigens are components of invading microorganism structures that are usually composed of proteins or polysaccharides.

Ag has to be recognized by the

  • Immunoglobulin receptor of B cells or
  • By the T cell receptor, when complexed with MHC

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 immunogens.

For cell-mediated immunity only proteins and some lipids/glycolipids serve as immunogen.

Properties of an Immunogen

  • Immunogenicity
  • Antigenicity

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

  • B cells + Ag   =           effector B cells (plasma cells) + memory B cells
  • T cells + Ag    =           effector T cells (e.g., CTLs, THs) + memory T cells

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.

A hapten is antigenic but incapable by itself of inducing a specific immune response, i.e., it lacks immunogenicity.


  • Immune cells do not interact with or recognize an entire immunogen instead, they recognize discrete sites on the macromolecule called epitopes. 
  • Epitopes are immunologically active regions of an immunogen that bind to antigen-specific membrane receptors on lymphocytes or to secreted antibodies.
  • B cells and T cells recognize different epitopes on the same antigenic molecule.
  • B cell bind epitopes that are present in highly accessible sites on the exposed surface of the immunogen.
  • T cells recognize only peptides combined with MHC molecules on the surface of APCs or altered self cells.


  • A substance that is non-immunogenic but which can react with the products of a specific immune response.
  • Haptens are small molecules that could never induce an immune response when administered by themselves but can when coupled to a carrier molecule.
  • Haptens have the property of antigenicity but not immunogenicity.

Factors influencing Immunogenicity

  1. Nature of the Immunogen
  • Foreignness
  • Molecular size
  • Chemical composition and heterogeneity
  • Ability to be  processed and presented with an MHC molecule on the surface of Antigen Presenting Cells (APCs) or altered self-cell

2. The biological system that the antigen encounters

  1. The genotype of the recipient animal
  2. Dosage and route of administration

Ⅰ. Foreignness

Antigens must be recognized as non-self by the biological system

The 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 (BSA) is injected into cow, rabbit, and chicken, the order of Immunogenicity will be:

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

This property is governed by Tolerance to self (specific unresponsiveness to self-antigens)

Ⅱ.  Molecular Size

A correlation exists between the 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

  • Chemical complexity contributes to immunogenicity
  • Copolymers composed of different amino acids or sugars are usually more immunogenic than homopolymers of their constituents.
  • All four levels of protein organization contribute to the structural complexity of a protein and hence affect its immunogenicity.

IV. Susceptibility to Ag Processing and Presentation

The development of both humoral and cell-mediated immune responses requires the interaction of T cells with Ag that has been processed and presented together with MHC molecules.

  • Large, insoluble macromolecules are generally more immunogenic than small, soluble macromolecules because of the ease of phagocytosis and processing.
  • Macromolecules that can not be degraded and presented are poor immunogens. For example, polymers of D-amino acids.

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

  • The genetic constitution of an immunized animal influences the type of immune response the animal manifests and the degree of response.
  • Genetic control of immune responsiveness is primarily confined to genes within MHC.
  • MHC gene products play a central role in determining the degree to which an animal responds to an immunogen.
  • Some substances are immunogenic in one individual but not in others (i.e.responders and non-responders).

Immunogen Dosage and Route of Administration

A: Amount of Immunogen 

  • An optimum dose is necessary to mount a good immune response.
  • An insufficient dose will not stimulate an immune response (fails to activate enough lymphocytes or can induce a state of immunologic unresponsiveness or tolerance).
  • Excessively high dose induces tolerance.

B: Times

  • Single-dose will not induce a strong response.
  • Repeated administration (boosters) increases clonal proliferation of antigen-specific T cells or B cells and thus increases the lymphocyte populations specific for the immunogen.
Primary Vs. Secondary Immune Response

C. Routes of Administration

  • Generally, the subcutaneous route is better than the intravenous or intragastric routes.
  • Route of administration strongly influences which immune organs and cell populations will be involved in the response. e.g., intravenous  (spleen); subcutaneous (local lymph nodes)


  1. Kuby Immunology, 8th Edition
  2. Roitt’s Essential Immunology, 13th Edition

Acharya Tankeshwar

Hello, thank you for visiting my blog. I am Tankeshwar Acharya. Blogging is my passion. As an asst. professor, I am teaching microbiology and immunology to medical and nursing students at PAHS, Nepal. I have been working as a microbiologist at Patan hospital for more than 10 years.

3 thoughts on “Antigen and Factors Affecting Immunogenicity

  1. Hello Assistance professor ! I need you to allow me to print this Note for due reason to Down load and print out , why is not printable ?

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