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    ANTIGEN (IMMUNOGEN)Prepared by: Victor B. Perlas Jr., RMT

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    IMMUNOGEN

    Any molecular structure that when introducedparenterally into an animal is capable of causingthe production of antibodies by that animal

    Macromolecule capable of triggering anadaptive response by inducing the formation of

    antibodies or sensitized T cells in animmunocompetent host.

    A substance that causes a detectable immuneresponse

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    ANTIGEN

    A substance that reacts with antibody orsensitized T cells but may not be able to evoke animmune response in the first place

    Refers to the ability of a substance to combinewith an antibody

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    ANTIGEN (IMMUNOGEN)

    TWO MAJOR CLASSES OF IMMUNOGENS:

    1. Thymic-dependent antigens require the helpof T cells for the formation of antibody. Mostimmunogens are thymic dependent

    2. Thymic-independent antigens or Thymic-

    efficient antigens stimulate antibodywithout interacting with T cells. The responseto these antigens is of the IgM class

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    IMMUNOGENECITY vs ANTIGENICITY

    IMMUNOGENECITY - inherent ability of asubstance (e.g. Immunogen) to produce animmune response

    ANTIGENICITY - implies both the ability toinduce a response and the ability to react with

    the products of that response. Antigens are theligands that react with the products of immuneresponse

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    ANTIGEN (IMMUNOGEN)EPITOPES (also called determinant groups or

    antigenic determinants) are the sides either on or

    within the antigen with which antibodies or T cellreceptors 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 partiallydegraded in vivo)

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    ANTIGEN (IMMUNOGEN)2. FunctionEpitopes determine the specificity of the antigen molecule,

    and therefore they are also known as determinantgroups. Epitopes are immunoreactive only if they arespatially accessible as a result of tertiary proteinstructure

    Paratope the area of an antibody molecule thatinteracts with an epitope

    Valence of an antigen equal to the number ofepitopes the antigen possesses

    Altering antigenicity - antigen molecules can beartificially manipulated by adding, altering or takingaway of epitopes

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    ANTIGEN (IMMUNOGEN)

    IMMUNOGENICITY

    The degree of immunogenicity of a molecule isinfluenced by several factors. The relationshipbetween these factors can be illustrated by thefollowing equation:

    Immunogenicity = (foreignness) (chemical

    complexity) (molecular size)

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    FACTORS AFFECTING IMMUNOGENECITY

    FOREIGNNESS an antigen must be foreign or aliento the host in which it makes contact

    1. The greater the phylogenetic difference, thegreater 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 ofthe same species (allograft or homograft foreign,and therefore can induce an immune response)

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    FACTORS AFFECTING IMMUNOGENECITY

    Syngeneic antigens found in geneticallyidentical individuals (syngeneic graft or isograft not foreign)

    Xenogeneic or heterelogous antigens found indifferent species (heterograft or xenograft

    highly immunogenic)

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    FACTORS AFFECTING IMMUNOGENECITY

    2. Heterogenetic antigens the ubiquity of theseantigens is exemplified by the Forssman

    antigen Heterophile antigens have in common one or

    more epitopes; they are cross-reacting3. Tissue-specific (organ-specific) antigens

    Thyroid thyroglobulin Myelin basic protein brain tissue Cell specific epitopes Sequestered antigens -

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    FACTORS AFFECTING IMMUNOGENECITY

    SIZE - the size of a molecule is important in itsability to induce an immune response. Usually

    the larger the molecule, the better theimmunogen, 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

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    FACTORS AFFECTING IMMUNOGENECITY

    3. Haptens

    Structure haptens are unique molecules

    sometimes called incomplete or partialantigens. They are usually too small to beimmunogenic

    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 butthey can react with the products of that response

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    FACTORS AFFECTING IMMUNOGENECITY

    Examples of haptens include antibiotics,analgesics, and other low-molecular weight

    compounds. Some macromolecules are alsohaptens and are unable to induce an immuneresponse when injected to an animal in a

    purified form.

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    FACTORS AFFECTING IMMUNOGENECITY

    4. A phenomenon known as the carrier effectexplains how haptens acquire immunogenicity.

    If a hapten is coupled with an immunogencarrier, the hapten becomes endowed withimmunogenicity, thus, is able to induce an

    immune response.

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    FACTORS AFFECTING IMMUNOGENECITY

    CHEMICAL COMPOSITION epitope diversitycontributes to the degree of immunogenicity :

    the more varied epitope composition of anantigen, the more likely different immuneresponses will be induced

    1. With the exception of pure lipids, most

    macromolecule can be immunogens2. Antigenic mosaic - each antigen has multiple

    epitopes; therefore, many differing antibodieswill be produced against cellular immunogens

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    OTHER FACTORS AFFECTINGIMMUNOGENECITYGENETIC COMPOSITION

    If a particular MHC antigen is not present for animmunogen, there will be no response

    HLA-A9 antigen high response to tetanustoxoid

    HLA-A5 antigen low response to tetanustoxoid

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    OTHER FACTORS AFFECTINGIMMUNOGENECITYROUTE, DOSAGE, AND TIMING

    Generally, intravenous and intraperitonealroutes are effective; the intradermal route offersstronger stimulus than the subcutaneous orintramuscular route (although there are

    exceptions to this) Dose response may be partially dependent onthe nature of immunogen processing. Generally,the smaller the dose, the less likely a response.

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    OTHER FACTORS AFFECTINGIMMUNOGENECITYADJUVANTS

    Substances administered with an immunogenthat increases the immune response (substancesadded 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 (0.5mg/mL); not used in humans

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    OTHER FACTORS AFFECTINGIMMUNOGENECITYADJUVANTSThe 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 immunogenadministration

    Amplify the proliferation of immunologicallycommitted cells

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    OTHER FACTORS AFFECTINGIMMUNOGENECITYSTRUCTURAL STABILITY Highly flexible molecules that have no fixed shape

    are poor immunogensDEGRADABILITY Molecules that are not biodegradable, such as

    polystyrene particles or asbestos, are

    nonimmunogenic because they cannot be processedin phagocytic cells of the body. Substances that arerapidly broken down in the body by plasmaenzymes, however, can be nonimmunogenic or veryweakly immunogenic

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    MOLECULAR DIFFERENCES IN EPITOPESTRUCTUREMolecular 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 theimmune response products

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    MOLECULAR DIFFERENCES IN EPITOPESTRUCTURE

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    MOLECULAR DIFFERENCES IN EPITOPESTRUCTURE2. Differences in the amino acid residues in the

    epitopic region of the proteins are critical to

    their immunologic specificity3. Differences in glycosidic linkages between

    monosaccharides also can be important in

    determining the immunologic specificity ofantibodies