IMMUNOLOGY ASSIGNMENT ANTIGEN: CHEMICAL AND MOLECULAR NATURE

SUBMITTED BY, S.SOWMYA M.KALAISELVI M.SARITHA

ANTIGEN:
Substances that are recognized as foreign and provoke immune responses are called antigens. Antigens include molecules such as proteins, nucleoproteins, polysaccharides and some glycolipids. Most antigens are large, complex molecule with molecular weight generally greater than 10000 Daltons (Da). The ability of a molecule to function as an antigen depends on its size, structural complexity, chemical nature and degree of foreignness to the host. Antigens are of four types: 1. Immmunogen 2. Tolerogen 3. Allergen 4. Vaccine IMMUNOGEN: It is the antigen that induce specific immune reponse. virus,fungi and parasites. Microbes: Bacteria,

Xenoantigeneic or allogeneic tissues or organs: grafted skin , transplanted bone marrow.

TOLEROGEN: Antigen that induce Immunologic tolerance. Immunologic tolerance is unresponsiveness to an antigen that is induced by prior exposure to that antigen.

ALLERGEN: Antigen that induce Anaphylaxis(severe immediate hypersensitivity reaction occurring as a result of rapid generalized mast-cell granulation)

VACCINE: Antigens that induce a protection immune response against microbes and are used to prevent diseases Killed vaccine: Rubella virus Attenuated vaccine: Measles Toxoid : Tetanus

BASED ON CHEMICAL NATURE: PROTEINS: Majority of immunogens are proteins (pure proteins or they may be glycoproteins or lipoproteins). Proteins are usually very good immunogens. POLYSACCHARIDES: Pure polysaccharides and lipopolysaccharides are good immunogens. NUCLEIC ACIDS: Nucleic acids are usually poorly immunogenic. However, they may become immunogenic when single stranded or when complexed with proteins. LIPIDS: In general lipids are non-immunogenic, although they may be haptens.

THE NATURE OF THE IMMUNOGEN CONTRIBUTES TO IMMUNOGENICITY: Immunogenicity is determined, in part, by four properties of the immunogen: Its foreignness, Molecular size, Chemical composition and complexity and Ability to be processed and presented with an MHC molecule on the surface of an antigen-presenting cell or altered self-cell. FOREIGNNESS: To induce an immune response, a molecule must be recognized as non self by the biological system. The ability to tolerate self antigens arises during lymphocyte development, during which immature lymphocytes are exposed to self-components. Any molecule that has not been exposed to immature lymphocytes during this critical period may be later recognized as nonself, or foreign, by the immune system. When an antigen is introduced into an organism, the degree of its immunogenicity depends on the degree of its foreignness. The greater the phylogenetic distance between two species, the greater the structural (and therefore the antigenic) disparity between them. For example, the common experimental antigen bovine serum albumin (BSA) is not immunogenic when injected into a cow but is strongly immunogenic when injected into a rabbit. There are some exceptions to this rule. Some macromolecules (e.g., collagen and cytochrome c) have been highly conserved throughout evolution and therefore display very little immunogenicity across diverse species lines. Conversely, some self-components (e.g.corneal tissue and sperm) are effectively sequestered from the immune system, so that if these tissues are injected even into the animal from which they originated, they will function as immunogens. MOLECULAR SIZE: There is a correlation between the size of a macromolecule and its immunogenicity. The most active immunogens tend to have a molecular mass of 100,000 daltons (Da). Generally,substances with a molecular mass less than 500010,000Da are poor immunogens, although a few substances with a molecular mass less than 1000Da have proven to be immunogenic. CHEMICAL COMPOSITION AND HETEROGENEITY: Size and foreignness are not sufficient to make a molecule immunogenic; other properties are needed as well.

 For example, synthetic homopolymers (polymers composed of a single amino acid or sugar) tend to lack immunogenicity regardless of their size. Copolymers composed of different amino acids or sugars are usually more immunogenic than homopolymers of their constituents Copolymers of sufficient size, if they contain 2 or more different amino acids, are immunogenic. The addition of aromatic amino acids such as tyrosine or phenyl alanine profoundly enhances the immunogenicity of these synthetic polymers. For example a synthetic copolymer of glutamic acid and lysine requires a minimum molecular weight of 30,00040,000 for immunogenicity. All four levels of protein organization primary, secondary, tertiary, and quaternarycontribute to the structural complexity of a protein and hence affect its immunogenicity.

SUSCEPTIBILITY TO ANTIGEN PROCESSING AND PRESENTATION: The development of both humoral and cell-mediated immune responses requires interaction of T cells with antigen that has been processed and presented together with MHC molecules. To TH cells , the antigen must be presented with class II MHC molecules on an antigen presenting cell; to TC cells , the antigen must be presented with class I MHC molecule on an altered self-cells. Macromolecules that cannot be degraded and presented with MHC molecules are poor immunogens. Large, insoluble macromolecules generally are more immunogenic than small, soluble ones because the larger molecules are more readily phagocytosed and processed. Intermolecular chemical cross-linking,induction of aggregation by heating and attachment to insoluble matrices have been routinely used to increase the insolubility of macromolecules thereby facilitating their phagocytosis and increasing their immunogenicity. EPITOPES: Epitopes are the immunologically active regions of an immunogen that bind to antigenspecific membrane receptors on lymphocytes or to secreted antibodies. B and T cells recognize different epitopes on the same antigenic molecule. For example, when mice were immunized with glucagon, a small human hormone of 29 amino acids, antibody was elicited to epitopes in the amino terminal portion, whereas the T cells responded only to epitopes in the carboxyl-terminal portion.

 Lymphocytes may interact with a complex antigen on several levels of antigen structure. An epitope on a protein antigen may involve elements of the primary, secondary, tertiary, and even quaternary structure of the protein. The recognition of antigens by T cells and B cells is fundamentally different. B cells recognize soluble antigen when it binds to their membrane-bound antibody. Because B cells bind antigen that is free in solution, the epitopes they recognize tend to be highly accessible sites on the exposed surface of the immunogen. Most T cells recognize only peptides combined with MHC molecules on the surface of antigen-presenting cells and altered self-cells; T-cell epitopes.

PROPERTIES OF B-CELL EPITOPES:

The ability to function as a B-cell epitope is determined by the nature of the antigenbinding site on the antibody molecules displayed by B cells. The B cell epitopes on native proteins generally are composed of hydrophilic amino acids on the protein surface that are topographically accessible to membrane-bound or free antibody.

 A small peptide epitope interacts with a deep, narrow groove in the antibody molecule,a protein epitope interacts with a larger, flatter complementary surface on the antibody molecule A B cell epitope must be accessible in order to be able to be bind to an antibody. B cell epitopes can contain sequential or nonsequential amino acids. Sequential B cell epitopes consist of amino acid residues contiguous along the polypeptide chain. Non sequential B-Cell epitopes, also called conformational determinants, are formed from noncontiguous segments of polypeptide chain that are brought into proximity by folding of a protein.

PROPERTIES OF T CELL EPITOPES:

T-cell epitopes-those epitopes recognized by T-cell receptors-generally consists of internal amino acid sequences. T-cell epitopes are rendered accessible to the immune system by antigen processing, which fragments the protein into small peptides that combine with class I or class II MHC molecules. The resulting peptide-MHC complexes are then displayed on the surface of antigen presenting cells. T-cell epitopes presented by MHC-class I molecules are typically peptides between 8-11 amino acids in length, whereas MHC Class II molecules present longer peptides.

References: 1. Kuby Immunology by Richard A Goldsby 2. Microbiology by Prescott