Factors That Influence Immunogenicity

To protect against infectious disease, the immune system must be able to recognize bacteria, bacterial products, fungi, parasites, and viruses as immunogens. In fact, the immune system actually recognizes particular macromolecules of an infectious agent, generally either proteins or polysaccharides. Proteins are the most potent immunogens, with polysaccha-rides ranking second. In contrast, lipids and nucleic acids of an infectious agent generally do not serve as immunogens unless they are complexed with proteins or polysaccharides. Immunologists tend to use proteins or polysaccharides as immunogens in most experimental studies of humoral immunity (Table 3-1). For cell-mediated immunity, only proteins and some lipids and glycolipids serve as immunogens. These molecules are not recognized directly. Proteins must first be processed into small peptides and then presented together with MHC molecules on the membrane of a cell before they can be recognized as immunogens. Recent work shows that those lipids and glycolipids that can elicit cellmediated immunity must also be combined with MHC-like membrane molecules called CD1 (see Chapter 8).

Molecular weight of some common experimental antigens used in immunology

Molecular weight of some common experimental antigens used in immunology

Antigen Approximate molecular mass (Da)

Bovine gamma globulin



Bovine serum albumin



Flagellin (monomer)


Hen egg-white lysozyme



Keyhole limpet hemocyanin



Ovalbumin (OVA)


Sperm whale myoglobin



Tetanus toxoid (TT)


Immunogenicity is not an intrinsic property of an antigen but rather depends on a number of properties of the particular biological system that the antigen encounters. The next two sections describe the properties that most immunogens share and the contribution that the biological system makes to the expression of immunogenicity.

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