Antigens (BTL-4014) PDF

Antigens BTL-4014  Introduction 1. Antigen (Ag) - the substances that might induce a specific immune response and subsequently react with the products of a specific immune response. 2. Properties of Ag - Immunogenicity Antigenicity 3. Immunogen...

Antigens BTL-4014  Introduction 1. Antigen (Ag) - the substances that might induce a specific immune response and subsequently react with the products of a specific immune response. 2. Properties of Ag - Immunogenicity Antigenicity 3. Immunogen - A substance that induces a specific immune response. 4.Hapten - A substance that is non-immunogenic but which can react with the products of a specific immune response. Haptens are small molecules which could never induce an immune response when administered by themselves, but can induce when coupled to a carrier molecule. Haptens have the property of antigenicity but not immunogenicity.  Antigenicity and Specificity Foreignness The immune system normally discriminates between self and non-self such that only foreign molecules are immunogenic. Specificity Antigenic determinant (epitope) The portion of the antigen that binds specifically with the binding site of an antibody or a receptor on a lymphocyte. The size of an epitope is approximately equivalent to 5-7 amino acids. Representation of Some Possible Antigenic Structures Description Example One epitope Haptens Many epitopes of the Many polysaccharides, same specificity homopolymers Many epitopes of different Proteins specificity Structure of epitope Conformational determinant Sequential determinant Epitopes recognized by B cells & T cells B cell epitope Antigenic peptide Degradation T cell epitope T cell epitope Natural protein B cell epitope and T cell epitope  Antigen T and B cell epitopes in a protein antigen  T cell epitope B cell epitope Receptor TCR BCR MHC necessary non-necessary Character linear short natural polypeptide peptide polysaccharides Size 8～12 aa(CD8+T) 5 ～15 aa 12～17aa(CD4+T) 5 ～7monosacch Type linear determinant conformational determinant ; linear determinant Location anywhere in Ag surface of Ag Common antigen and cross-reaction  Factors influencing immunogenicity A. Contribution of the Immunogen 1. Chemical Composition – Proteins and polysaccharides are more immunogenic. 2. Size - There is not absolute size above which a substance will be immunogenic. In general, the larger the molecule the more immunogenic it is likely to be. 3. Chemical Complexity - an increase in the chemical complexity of a compound is accompanied by an increase in its immunogenicity 4. Conformation and accessibility 5. Physical form - In general particulate antigens are more immunogenic than soluble ones and denatured antigens are more immunogenic than the native form. B. Contribution of the Biological System 1. Genetic Factors - Some substances are immunogenic in one species but not in another. Similarly, some substances are immunogenic in one individual but not in others (i.e. responders and non-responders). 2. Age - Age can also influence immunogenicity. Usually the very young and the very old have a diminished ability to mount immune response in response to an immunogen. C. Method of Administration 1. Dose - The dose of administration of an immunogen can influence its immunogenicity. 2. Route - Generally the subcutaneous route is better than the intravenous or intragastric routes. - The route of antigen administration can also alter the nature of the response 3. Adjuvants  Adjuvant It is a substance which, when mixed with an immunogen, enhances the immune response against the immunogen. The use of adjuvants, however, is often hampered by undesirable side effects such as fever and inflammation. Alum, Freund’s complete/incomplete adjuvant, LPS, etc.  Types of Antigens Thymus-dependent antigen (TD-Ag) Thymus-independent antigen (TI-Ag) Relative: – Xenogenic antigen – Allogenic antigen – Autoantigen – Heterophilic antigen – Idiotypic antigen TD-Ag T-dependent antigens are those that do not directly stimulate the production of antibody without the help of T cells. Proteins are T-dependent antigens. TI-Ag T-independent antigens are antigens which can directly stimulate the B cells to produce antibody without the requirement for T cell help. In general, polysaccharides are T- independent antigens. The responses to these antigens differ from the responses to other antigens. TI-Ag T-independent antigens can be subdivided into Type-1 and Type-2 based on their ability to polyclonally activate B cells. Type 1 T-independent antigens are polyclonal activators while Type 2 are not.  T-dependent (TD) Antigen T-independent (TI) Antigen Bacterial cell wall components, Capsular Soluble proteins polysaccharide, flagella etc. Antigen is processed and displayed on the surface of antigen presenting cells (B Cells) in Antigen processing is not needed association with MHC-II. Immunogenic over wide range of dose Dose dependent immunogenicity No polyclonal activation i.e. Activate B cells Polyclonal activation of B cells occur in high monoclonally doses of Type-I TI Antigens Immunologic memory present No immunologic memory Affinity maturation- Yes Affinity maturation- No Isotype switching occurs (i.e. antibodies of all No isotype switching classes are produced) (Antibody response is restricted to IgM and IgG3) Activate mature B cells only Activate both mature and immature B cells  Types of antigens Xenogenic Ag An antigen common to members of one species but not to members of other species. Allogenic Ag Individuals of a species differ in alleles (are allogeneic) and the antigenic differences will cause an immune response to allografts. The antigens concerned are often of the MHC and are referred to as allogenic antigens. Autoantigen The antigens of an organisms own cells and cell products are self antigens to the immune system of that organism. Clones of immune cells reactive with self antigens are normally eliminated. Heterophilic Ag (Forssman antigen) A cross-reacting antigen that appears in widely ranging species such as bacteria, animals, and humans (cancer cells). Idiotypic Ag The combined antigenic determinants (idiotopes) found on antibodies of an individual that are directed at a particular antigen. Such antigenic determinants are found only in the variable region.  Superantigen (SAg) Immune system encounters a conventional TD-Ag, only a small fraction (1 in 106 -104) of the T cell population is able to recognize the antigen and become activated (monoclonal/oligoclonal response). However, there are some Ags which polyclonally activate some subtypes of the T cells (up to 25%). e.g., Mls (Minor lymphocyte stimulating Ag)