Antigen PDF

Antigens Dr/ Fahad Alzowahi Assistant professor in Microbiology Antigen: Is defined as a foreign substance or that induces the production of specific antibodies or the activation of specific immune cells, or that interacts specifically with the products of the immune response. Im...

Antigens Dr/ Fahad Alzowahi Assistant professor in Microbiology Antigen: Is defined as a foreign substance or that induces the production of specific antibodies or the activation of specific immune cells, or that interacts specifically with the products of the immune response. Immunogen: Is a foreign substance that induces a specific immune response, or is a stimulus that produces a humoral or cell- mediated immune response. All immunogens are antigens but not all antigens are immunogens, (table 4 & figure 20). Epitope: The portion of an antigen that is recognized and bound by an Ab or TCR/MHC complex (aka antigenic determinant).  Table (4): Differences between Antigen and Immunogen. Antigen Immunogen A substance specifically bind to An antigen capable of inducing antibodies or a cell surface receptors of an immune response and is B cells and T cells. unable to bind to the immune response products. Can be either immunogenic or non- Immunogenic. immunogenic. Not all are immunogens. All are antigens. Can be either proteins, Normally proteins and large polysaccharides, lipids or nucleic acids. polysaccharides. Haptens are low-molecular weight Haptens become immunogenic when molecules, which bind to antibodies. binding to larger carrier molecules. Fig.(20): Antigens and immunogens of microbial cell. Antigenicity: Is the ability of an antigen to bind specifically with the final products of the adaptive immunity (i.e., antibodies and/or T-cell receptors). Immunogenicity: Is the ability of an antigen to induce a humoral and/or cell-mediated immune response. Therefore, it is clear that, all immunogens are antigens, but not all antigens are immunogens.  Factors that affect immunogenicity Immunogenicity is determined by five properties of the immunogen (complete antigen) : 1- Foreignness: Immunogens must be recognized as non-self-antigens by the immune system. The degree of immunogenicity is dependent upon the degree of foreignness. The greater the phylogenetic distance between species the greater the chance of immunogenicity. 2- Molecular weight: There is a strong correlation between molecular weight and immunogenicity.  If the immunogen has high molecular weight with specific characters for good immunogen, it can stimulates immune cells easily and produce good immune response either cell-mediated or humoral immunity. The best immunogens are having Mw of 100,000 Da, while small molecules 5-10,000 Da are generally poor immunogens. 3- Chemical nature and stability : The chemical structure of an immunogen must be stable in different temperature, pH, and biological solutions. Moreover, chemical complexity contributes to immunoge- nicity, i.e. an immunogen composed of different amino acids are usually more immunogenic than homopolymers of their constituents.  Proteins with more complexity in primary structure and those showing secondary, tertiary, and quaternary structure increase immunogenicity. 4- Physical form: Insoluble (particulate) immunogen is more immunogenic than soluble immunogen and denatured immunogen more immunogenic than the native form. 5- Degradability: Immunogen that is easily phagocytized is generally more immunogenic. This is because that the phagocytized immunogen is processed and presented to T-helper cells by an antigen presenting cell (APC).  Other forms of Antigens Hapten (partial or incomplete antigen): Is a foreign substance of low molecular weight which cannot induce an adaptive immune response by itself (i.e. it lack immunogenicity), but can elicit an immune response only when combined to a large carrier such as a protein. Allergen: It is an antigen which can provoke a hypersensit-ivity reaction (allergy) in individuals already sensitized with the allergen. Superantigen: Is defined as an antigen that causes non-specific activation of T-cells, resulting in polyclonal T-cell activation and mass- ive cytokine release. Tolerogen: It is an antigen (usually a soluble form) which induces immunologic tolerance. Auto-antigen: Is defined as an antigen that is recognized by the immune system of patients suffering from a specific autoimmune disease. Alloantigens (isoantigens): Are antigens found in different members of the same species (the red blood cell antigens A and B are examples). Heterophile antigens: Are identical antigens found in the cells and tissues of different species, e.g. Cross-reacting microbial antigens, etc. It is the antigen which shared by different species. T-dependent antigen: Antigens that require the assistance of T cells to induce the formation of specific antibodies. T-independent antigen: Polysaccharides (usually) that stimulate B cells directly.  Chemical nature of antigens Proteins: The majority of immunogens (complete antigens) are proteins or proteins conjugated with other molecules such as polysaccharides to form glycoproteins, and lipids to form lipoproteins. In general, proteins are usually very good immunogens. Polysaccharides: In general, polysaccharides and lipopolysaccharides are good immunogens. Nucleic acids: Nucleic acids are usually poorly immunogenic. Lipids: lipids are non-immunogenic molecules and may be considered as haptens. In general, lipids and nucleic acids are immunogenic only when combined with proteins or polysaccharides. Classification of Antigens: According to antigen’s origin: 1- Exogenous (external) antigens (non-self-antigens): They are antigens that are entered the body from the outside by inhalation, ingestion, or injection. External antigens may be (bacterial structures and toxins, viruses, fungi and parasites).  Presented by Antigen Presenting Cells (APC’s) such as macrophages, B-cells, and some dendritic cells. APC’s then present the fragments to T helper cells (CD4+) by the use of MHC class II molecules on their surface. 2- Endogenous antigens: Endogenous antigens are generated within normal cells as a result of normal cell metabolism, or because of viral or intracellular bacterial infection. The fragments are then presented on the cell surface in the complex with MHC class I molecules which is recognized by T cytotoxic cell (CD8+). If activated cytotoxic CD8+ T cells recognize them, the T cells secrete various toxins that cause the lysis or apoptosis (falling off) of the infected cell.  3- Autoantigens (self-antigens): An autoantigen is usually a normal protein or protein complex (and sometimes DNA or RNA) that is recognized by the immune system of patients suffering from a specific autoimmune disease. These antigens under normal conditions should not be the target of the immune system, but under some circumstances, their associated T cells are not suppressed and start attack the infected normal cell (autoantigen). 4- Tumor antigens Tumor antigens are those antigens that are presented by MHC class I or MHC class II molecules on the surface of tumor cells only.  Antigens found only on such cells are called tumor-specific antigens (TSAs) and generally result from a tumor-specific mutation. When these antigens are also expressed at lower levels on healthy cells then they are called Tumor- associated antigens (TAAs). Cytotoxic T lymphocytes that recognize these antigens may be able to destroy tumor cells. According to immune response: 1- Complete Antigen or Immunogen A complete antigen is able to induce antibody formation and produce a specific and observable reaction with the produced antibody.  2. Incomplete Antigen or Hapten: Are substances which are incapable of inducing antibody formation by themselves, but can be capable of inducing antibodies on combining with larger molecules (normally proteins) which serve as carriers, (figure-21). Fig.(21): Transformation of hapten to complete antigen.  Adjuvants (to help) Adjuvants are substances that, when mixed with an antigen and injected with it, enhance the immunogenicity of that antigen. Adjuvants are often used to boost the immune response when an antigen has low immunogenicity or when only small amounts of an antigen are available. It acts by producing a local inflammatory response that attracts a large number of immune system cells to the injection site. It is administrated with the antigen in case of vaccination, (figure-22). Examples of Adjuvants:  Aluminum potassium sulfate (alum): prolongs the persistence of antigen.  When an antigen is mixed with alum, the salt precipitates the antigen. Injection of this alum precipitate results in a slower release of antigen from the injection site, so that the effective time of exposure to the antigen increases from a few days without adjuvant to several weeks with the adjuvant. The alum precipitate also increases the size of the antigen, thus increasing the phagocytosis. Freund’s complete adjuvant: Consists of mineral oil, emulsifier, and killed mycobacteria (0.5 mg/mL). Freund’s adjuvant produces granulomas, or large areas of scar tissue, and thus is not used in humans. Aluminum salts: Are the only ones approved for clinical use in the United States, and these are used to complex with the immuno- gen to increase its size and to prevent a rapid escape from the tissues. It must be injected into the muscle to work. The hepatitis B vaccination is an example of using this type of adjuvant. Fig.(22): Key roles of adjuvants in modern vaccines. Mechanism action of Adjuvants: The precise mechanism of action of adjuvants remains uncertain. Adjuvants are believed to bring about: a. Direct increase in number of cells involved in antibody production. b. Ensure a more efficient processing of antigen. c. Prolong the duration of antigen in the immunized animal. d. Increase the synthesis and release of antibody.  Table (5): Differences between Hapten and Adjuvant Hapten Adjuvant Small. Can be more complex. More likely chemical. Pharmacological. When conjugated can induce an Typically not conjugated and does not immune response; induce an immune response on its own - Anti-hapten antibodies. even when it is part of the combined - The hapten becomes an antigen. vaccine.