ANTIGEN (IMMUNOGEN)

Prepared by: Victor B. Perlas Jr., RMT

IMMUNOGEN
Any molecular structure that when introduced parenterally into an animal is capable of causing the production of antibodies by that animal Macromolecule capable of triggering an adaptive response by inducing the formation of antibodies or sensitized T cells in an immunocompetent host. A substance that causes a detectable immune response

ANTIGEN
A substance that reacts with antibody or sensitized T cells but may not be able to evoke an immune response in the first place Refers to the ability of a substance to combine with an antibody

ANTIGEN (IMMUNOGEN)
TWO MAJOR CLASSES OF IMMUNOGENS: 1. Thymic-dependent antigens require the help of T cells for the formation of antibody. Most immunogens are thymic dependent 2. Thymic-independent antigens or Thymicefficient antigens stimulate antibody without interacting with T cells. The response to these antigens is of the IgM class

IMMUNOGENECITY vs ANTIGENICITY
IMMUNOGENECITY - inherent ability of a substance (e.g. Immunogen) to produce an immune response ANTIGENICITY - implies both the ability to induce a response and the ability to react with the products of that response. Antigens are the ligands that react with the products of immune response

ANTIGEN (IMMUNOGEN)
EPITOPES (also called determinant groups or antigenic determinants) are the sides either on or within the antigen with which antibodies or T cell receptors react 1. Structure Size epitopes are very small (four or five amino acids or monosaccharide residues) Conformation can be linear or conformational Site on antigens surface (topographic epitopes); internal epitopes (antigens have been partially degraded in vivo)

ANTIGEN (IMMUNOGEN)
2. Function Epitopes determine the specificity of the antigen molecule, and therefore they are also known as determinant groups. Epitopes are immunoreactive only if they are spatially accessible as a result of tertiary protein structure Paratope the area of an antibody molecule that interacts with an epitope Valence of an antigen equal to the number of epitopes the antigen possesses Altering antigenicity - antigen molecules can be artificially manipulated by adding, altering or taking away of epitopes

ANTIGEN (IMMUNOGEN)
IMMUNOGENICITY The degree of immunogenicity of a molecule is influenced by several factors. The relationship between these factors can be illustrated by the following equation:

Immunogenicity = (foreignness) (chemical complexity) (molecular size)

FACTORS AFFECTING IMMUNOGENECITY

FOREIGNNESS an antigen must be foreign or alien to the host in which it makes contact 1. The greater the phylogenetic difference, the greater the immune response Autoantigen derived from the same individual (autograft not foreign and will not attacked by the immune response) Alloantigen derived from different individual of the same species (allograft or homograft foreign, and therefore can induce an immune response)

FACTORS AFFECTING IMMUNOGENECITY

Syngeneic antigens found in genetically identical individuals (syngeneic graft or isograft not foreign) Xenogeneic or heterelogous antigens found in different species (heterograft or xenograft highly immunogenic)

FACTORS AFFECTING IMMUNOGENECITY

2. Heterogenetic antigens the ubiquity of these antigens is exemplified by the Forssman antigen Heterophile antigens have in common one or more epitopes; they are cross-reacting 3. Tissue-specific (organ-specific) antigens Thyroid thyroglobulin Myelin basic protein brain tissue Cell specific epitopes Sequestered antigens -

FACTORS AFFECTING IMMUNOGENECITY

SIZE - the size of a molecule is important in its ability to induce an immune response. Usually the larger the molecule, the better the immunogen, although there are exemptions. 1. As a general rule, molecules smaller than 5-10 kDa are non-immunogenic. 2. Size is very important for several reasons: Number and variety of epitopes Larger molecules are phagocytized

FACTORS AFFECTING IMMUNOGENECITY

3. Haptens Structure haptens are unique molecules sometimes called incomplete or partial antigens. They are usually too small to be immunogenic Function haptens can react with immune lymphocytes or antibodies once they are formed, but they are not immunogenic by themselves. Haptens cannot induce an immune response but they can react with the products of that response

FACTORS AFFECTING IMMUNOGENECITY

Examples of haptens include antibiotics, analgesics, and other low-molecular weight compounds. Some macromolecules are also haptens and are unable to induce an immune response when injected to an animal in a purified form.

FACTORS AFFECTING IMMUNOGENECITY

4. A phenomenon known as the carrier effect explains how haptens acquire immunogenicity. If a hapten is coupled with an immunogen carrier, the hapten becomes endowed with immunogenicity, thus, is able to induce an immune response.

FACTORS AFFECTING IMMUNOGENECITY

CHEMICAL COMPOSITION epitope diversity contributes to the degree of immunogenicity : the more varied epitope composition of an antigen, the more likely different immune responses will be induced 1. With the exception of pure lipids, most macromolecule can be immunogens 2. Antigenic mosaic - each antigen has multiple epitopes; therefore, many differing antibodies will be produced against cellular immunogens

OTHER FACTORS AFFECTING IMMUNOGENECITY

GENETIC COMPOSITION If a particular MHC antigen is not present for an immunogen, there will be no response HLA-A9 antigen high response to tetanus toxoid HLA-A5 antigen low response to tetanus toxoid

OTHER FACTORS AFFECTING IMMUNOGENECITY

ROUTE, DOSAGE, AND TIMING Generally, intravenous and intraperitoneal routes are effective; the intradermal route offers stronger stimulus than the subcutaneous or intramuscular route (although there are exceptions to this) Dose response may be partially dependent on the nature of immunogen processing. Generally, the smaller the dose, the less likely a response.

OTHER FACTORS AFFECTING IMMUNOGENECITY

ADJUVANTS Substances administered with an immunogen that increases the immune response (substances added to vaccines) Aluminum salts only ones approved for clinical use in USA; added to hepatitis B vaccines Freunds complete adjuvant consists of mineral oil, emulsifier, killed mycobacteria (0.5 mg/mL); not used in humans

OTHER FACTORS AFFECTING IMMUNOGENECITY

ADJUVANTS The mechanisms by which adjuvants exert their biologic effect: Act as depot and prolong the period of exposure to the immunogen Irritant that increases the inflammatory response at the site of immunogen administration Amplify the proliferation of immunologically committed cells

OTHER FACTORS AFFECTING IMMUNOGENECITY

STRUCTURAL STABILITY Highly flexible molecules that have no fixed shape are poor immunogens DEGRADABILITY Molecules that are not biodegradable, such as polystyrene particles or asbestos, are nonimmunogenic because they cannot be processed in phagocytic cells of the body. Substances that are rapidly broken down in the body by plasma enzymes, however, can be nonimmunogenic or very weakly immunogenic

MOLECULAR DIFFERENCES IN EPITOPE STRUCTURE

Molecular differences in epitope structure forms the basis of the exquisite specificity of the immune response 1. Differences in position of the charged groups within a molecule dictate the specificity of the immune response products

MOLECULAR DIFFERENCES IN EPITOPE STRUCTURE

MOLECULAR DIFFERENCES IN EPITOPE STRUCTURE

2. Differences in the amino acid residues in the epitopic region of the proteins are critical to their immunologic specificity 3. Differences in glycosidic linkages between monosaccharides also can be important in determining the immunologic specificity of antibodies