Antigens PDF

Antigens Felix N. Toka DVM, PhD, DSc Objectives for this topic Define what antigens are Emphasize two cardinal features of antigens Describe properties of antigens Describe types of antigens Antigens The word antigen arose as a condensation of the words antibody generator Molecul...

Antigens Felix N. Toka DVM, PhD, DSc Objectives for this topic Define what antigens are Emphasize two cardinal features of antigens Describe properties of antigens Describe types of antigens Antigens The word antigen arose as a condensation of the words antibody generator Molecules that induce an immune response when introduced into the body Antigens are molecules or pieces of molecules that bind to antibodies, MHC molecules or lymphocyte receptors (TCRs and BCRs)  There are two subcategories of antigens: immunogens haptens Immunogens - substances capable of stimulating an immune response Haptens - substances that will not by themselves stimulate an immune response but can do so when complexed with a larger molecule, such as a host protein  Antigens have two cardinal features: immunogenicity and antigenicity Immunogenicity - antigens are capable of inducing an immune response (in form of T cells, B cells (antibodies, Ab)) Antigenicity - antigens are capable of binding products of the immune response that they induced (e.g., lymphocytes or antibodies)  Epitope or antigenic determinant – is a part of an antigen that is actually responsible for inducing the immune response and binding to the products of the immune response (lymphocyte receptors and antibodies) http://edoc.hu-berlin.de/dissertationen/voigt-antje-2004-04-19/HTML/chapter1.html Antigenic determinants Sources of antigens Infectious agents (Microbial antigens): Bacteria Viruses Parasites Fungi Altered self antigens e.g., Tumors Bacterial antigens Viral antigens Structural antigens (1) Non-structural antigens (2) Fungal antigens faculty.ccbcmd.edu Parasitic antigens Challenges of parasitic antigens http://www.malariavaccine.org/malvac-lifecycle.php Non-microbial antigens  Non-microbial antigens Cell surface antigens A Blood group Ag A B RBC B AB O Rh Factor (Rhesus macacus) Rh A +/- B +/- AB +/- O +/- Non-microbial Antigens Cell Surface Antigens MHC class I MHC class II Nucleated cell Major Histocompatibility Complex Factors affecting immunogenicity of antigens Foreignness – the immune system distinguishes between self and non- self and only non-self substances are immunogenic and induce immune response (with exceptions) Size – there is no absolute size at which antigens become more immunogenic, however, the larger the antigen the more immunogenic it can be Chemical composition – complex molecules are usually immunogenic (chance of diverse antigenic determinants)  Physical properties particulate antigens are more immunogenic than soluble antigens, denatured antigens are more immunogenic than native forms (denaturation exposes more antigenic determinants) https://prezi.com Degradability – antigens that are phagocytosed and easily degraded are usually highly immunogenic  Genetic factors – some antigens are more immunogenic for a given species than for the other. Similarly, some antigens are more immunogenic for an individual than the other Species or individuals may have genetic variations in genes encoding antigen receptors on both T or B cells Age – young or old individuals usually have less capability to mount an immune response compared to the middle aged in relation to the same antigen  Chemical nature of antigens Proteins – by far the largest group of antigens. Most proteins are highly immunogenic (pure proteins, glycoproteins or lipoproteins) Polysaccharides – pure polysaccharides and lipopolysaccharides are usually good immunogens (pneumococcal polysaccharides may require conjugation)  Nucleic acids – weak antigens, may become highly immunogenic when conjugated to proteins Lipids – generally not immunogenic, but some may be haptens How are microbial antigens introduced into body? Infections  Route of administration (vaccine antigens) Per os (e.g., Polio vaccine) Intranasal (e.g., FluMist) Intramuscular (most vaccines) Intravenous (rarely used) Intradermal (BCG for TB vaccine) Subcutaneous (most vaccines) Adjuvant - a substance that enhances the body's immune response to an antigen  Types of antigens 1. T-independent antigens – antigens that directly stimulate B lymphocytes to produce antibodies without the need of helper T cells, e.g., lipopolisaccharides are T-independent antigens spot.pcc.edu-  Properties of T-independent antigens have a polymeric structure, i.e., – the same antigenic determinant repeats several times throughout the length of the antigen  may activate lymphocytes polyclonally – i.e., even B cells of different antigenic specificity may be activated resistant to degradation – do not easily degrade, therefore, may last longer and stimulate B lymphocytes much longer 2. T-dependent antigens - antigens that indirectly stimulate B lymphocytes to produce antibodies The presence of helper T cells is required for stimulation, hence the name T-dependent Proteins are mostly T-dependent antigens Structurally, they contain a few copies each of various antigenic determinants throughout the length of the antigen www.slideshare.net- 3. Superantigens When the immune system encounters a T-dependent antigen, only antigen specific lymphocytes respond and become activated (monoclonal response) However, other antigens such as „superantigens” can activate a large number of lymphocytes at one time (non-specifically)  Superantigens are mostly derived from bacteria or viruses They bind to the variable domain of the β (Vβ) chain in the T cell receptor (TCR) of CD4+ T cells and the α chain of the MHC class II molecule on antigen presenting cells smallcollation.blogspot.com-  Binding of the superantigen to the TCR and MHC class II molecule induces a very strong signal that activates a large number of T cells, polyclonally Polyclonal activation of helper T lymphocytes leads to excessive production of IL-1, IL-2, IL-6, TNFα, MIP-1α and MIP-1β which may lead to systemic toxicity ftp.fal 4. Haptens Small non-immunogenic substances (e.g., metabolites of antibiotics such as penicilloyl from Penicillin) On their own cannot induce an immune response May induce an immune response only if they become conjugated to a carrier e.g., a protein  In other words haptens are incomplete antigens, because they lack immunogenicity 5. Autoantigens – are natural constituents of the body, as opposed to foreign antigens They play a role autoimmunity – reaction of the immune system against host antigens  Exogenous antigens – antigens that have entered the body from outside e.g., by inhalation, ingestion Endogenous antigens – antigens that are generated within cells as a result of normal cell metabolism or because of viral or intracellular bacterial infection