Types of Antigens PDF

Types of Antigens Immunology Course Lecture 6 Immunogen vs. Antigen Definitions: Immunogen: – A substance that induces an immune response. – Must be capable of being recognized by the immune system, typically larger and more complex. Antigen: – A substance that is recognized...

Types of Antigens Immunology Course Lecture 6 Immunogen vs. Antigen Definitions: Immunogen: – A substance that induces an immune response. – Must be capable of being recognized by the immune system, typically larger and more complex. Antigen: – A substance that is recognized by the immune system and can bind to specific antibodies. – Can be immunogenic or non-immunogenic (not all antigens induce a response). Immunogen vs. Antigen Key Differences: Feature Immunogen Antigen Definition Induces an immune response Binds specifically to an antibody Example Pathogens (e.g., bacteria, viruses) Proteins, polysaccharides, haptens Size Typically larger (≥ 5 kDa) Can vary in size; includes haptens Function Triggers adaptive immunity Targets for immune cells or antibodies All immunogens are antigens, but not all antigens are immunogens. Understanding the distinction is crucial for vaccine development and immunotherapy. Antigen is a substance that reacts with an antibody Immunogens induce an immune response Overvie Most antigens are w immunogens There are a wide variety of features that largely determine immunogenicity  Features that determine immunogenicity 1. Recognition of foreignness: The immune system reacts when it detects something that doesn’t belong to the body. 2. Size: Bigger antigens (over 10,000 Daltons) tend to trigger stronger immune responses. However, small molecules can also act as antigens if they attach to larger proteins or sugars (these small molecules are called haptens). 3. Chemical and structural complexity: The more complicated the structure of the antigen, the stronger the immune response. 4. Genetic constitution of the host: Different animals or people may respond differently to the same antigen because their genes, especially the ones controlling immune responses, are different. 5. Dosage, route, and timing: How much of the antigen is given, how it enters the body (for example, through a shot or by mouth), and when it’s given can all affect how strong the immune response is. 1. Size: 1. Increased immunogenicity (stronger response): Larger proteins. 2. Decreased immunogenicity (weaker response): Smaller proteins (less than 2500 molecular weight). 2. Dose: 1. Increased immunogenicity: A moderate (intermediate) amount of protein. 2. Decreased immunogenicity: Very high or very low amounts of protein. 3. Route (How it's introduced into the body): 1. Increased immunogenicity: Injected under the skin (subcutaneous) or into the body cavity (intraperitoneal). 2. Decreased immunogenicity: Directly into the bloodstream (intravenous) or through the stomach (intragastric). 4. Composition: 1. Increased immunogenicity: Complex proteins. 2. Decreased immunogenicity: Simple proteins. 1. Form: 1. Increased immunogenicity: When proteins are in a particulate form (e.g., small solid particles) or are denatured (changed from their natural structure). 2. Decreased immunogenicity: When proteins are soluble (can dissolve in water) or are in their natural form (native). 2. Similarity to self proteins (proteins in the body): 1. Increased immunogenicity: Proteins that are very different from the body's own proteins. 2. Decreased immunogenicity: Proteins that closely resemble the body's own proteins. 3. Adjuvants (substances added to boost the immune response): 1. Increased immunogenicity: If the protein is released slowly or if bacteria are present. 2. Decreased immunogenicity: If the protein is released quickly or if no bacteria are present. 4. Interaction with host MHC (Major Histocompatibility Complex, important for immune recognition): 1. Increased immunogenicity: If the protein interacts effectively with MHC.  Classification of Antigens Based on Chemical Nature (Structural) Proteins – Major type, highly immunogenic – Examples: enzymes, structural proteins Polysaccharides – Often found on the surface of bacteria – Examples: capsular polysaccharides Lipids and Nucleic Acids – Less immunogenic, but can elicit responses in certain contexts  Structural types of antigens Antigens are usually proteins, peptides (amino acid chains) and polysaccharides (chains of monosaccharides/simple sugars) Lipids and nucleic acids become antigens only when combined with proteins and polysaccharides.  Structural types of antigens In general, saccharides and lipids (as PROTIEN opposed to peptides) qualify as antigens but not as immunogens since they cannot elicit an immune response on PEPTIDE their own. Furthermore, for a peptide to induce an immune response (activation of T-cells SACCHARIDE by antigen-presenting cells) it must be a large enough size, since peptides too LIPIDS & Nucleic small will also not elicit an immune acid response. Level of Immunogenicity  Classification of Antigens Based on Origin Exogenous Antigens: These come from outside the body. Examples include pathogens like bacteria, viruses, or toxins that enter the body from the external environment. Endogenous Antigens: These come from inside the body. Examples include cancerous cells or autoantigens (which are normal body cells mistakenly targeted by the immune system).  V Exogenous Antigens S Endogenous Antigens Classification of Antigens Based on Origin  EPITOPE The epitope is an antigenic determinant, and these are small in size. These may be 4-5 aminoacid or monosaccharides. These may be present on: 1. The surface is called topographical. 2. Internal only expressed after processing by the APC. The antigen has a variable number of epitopes varying from one to hundreds, and this is called valency of antigen. An epitope can be altered in the configuration by combination with other substances. Autoantigens An autoantigen is usually a normal protein or complex of proteins (and sometimes DNA or RNA) that is recognized by the immune system of patients suffering from a specific autoimmune disease. under normal conditions these antigens should not be the target of the immune system, but mainly due to genetic and environmental factors the normal immunological tolerance for such an antigen has been lost in these patients. Tumor antigens Tumor antigens are those antigens that are presented by the MHC I molecules on the surface of tumor cells. These antigens can sometimes be presented only by tumor cells and never by the normal ones. In this case, they are called tumor-specific antigens (TSAs) and typically result from a tumor specific mutation.  Super antigens Superantigens are a unique class of antigens that can trigger an intense immune response by simultaneously activating a large number of T cells. Unlike conventional antigens, which are presented by antigen-presenting cells (APCs) through specific MHC molecules, superantigens bind directly to the MHC class II molecules and T cell receptors (TCRs) outside of the conventional antigen-binding site. This allows them to activate up to 20% of the body's T cells, leading to a massive release of cytokines and a robust immune response. Examples of Super antigens Staphylococcal Enterotoxins (SEs) Toxic Shock Syndrome Toxin-1 (TSST-1)  Super antigens Mechanism of Action Binding to MHC and TCR: Super antigens bind directly to the variable region of the TCR and to the MHC class II molecule, which enables them to activate T cells without the need for specific antigen processing. Massive T Cell Activation: This unique binding mechanism results in the activation of a large proportion of T cells. Normally, T cell activation is specific and requires a particular antigen; super antigens bypass this specificity. Cytokine Release: The activation of T cells leads to the secretion of large amounts of pro-inflammatory cytokines (e.g., IL-2, TNF-α), which can result in: – Systemic inflammatory response – Toxic shock syndrome – Autoimmune reactions Potential for Immunopathology: The overwhelming immune response can lead to damage in tissues and organs, resulting in severe clinical manifestations.  Haptens Haptens are small molecules that, by themselves, are not immunogenic—they cannot elicit an immune response on their own. However, when haptens bind to larger carrier proteins, they can form a complete antigenic structure, allowing them to provoke an immune response. This property makes haptens an important concept in immunology and pharmacology. (eg. Penicillin) Characteristics of Haptens: Molecular Weight: Haptens are typically low molecular weight compounds (usually less than 1000 Da), which is why they cannot stimulate an immune response independently. Chemical Structure: Haptens can be derived from a variety of chemical structures, including small organic molecules, peptides, and certain drug metabolites. Immunogenicity: Upon conjugation with a carrier protein, haptens can become immunogenic, meaning they can be recognized by the immune system, leading to the production of antibodies.  Antigen-Antibody interaction Antigens are specifically bound by antibodies (Ab) or a cell surface version of Ab ~ B cell antigen receptor (BCR) Antigens are "targeted" by antibodies The Antibodies has specificities towards any particular antigen due to immunological process (how?)  Antigen-Antibody interaction The antibody is "match" the antigen when it can bind to it due to an adaptation in a region of the antibody Accordingly, different antibodies are produced, each able to bind a different antigen while sharing the same basic structure In most cases, an adapted antibody can only react to and bind one specific antigen In some instances, however, antibodies may cross-react and bind more than one antigen. Practical Applications Use of antigens in vaccines Therapeutic antibodies and their targets Considerations for drug development and immunotherapy