Antigen and Super Antigen PDF

ANTIGEN AND SUPER ANTIGEN Dr Eman Muhammad Majeed Antigens (Ags) Definitions  Antigens are substances that can induce the production of antibody.(antibody generator).  Antigens are substances that can induce both types of immune response and bind to products of immune response. (Is a mol...

ANTIGEN AND SUPER ANTIGEN Dr Eman Muhammad Majeed Antigens (Ags) Definitions  Antigens are substances that can induce the production of antibody.(antibody generator).  Antigens are substances that can induce both types of immune response and bind to products of immune response. (Is a molecule that recognized by antigen receptors of either B or T cells).  Antigens are not just a components of foreign substances (pathogens). A large variety of self molecule can serve as Ags as well provoking autoimmune responses. Characteristics of Ag  Immunogenicity: The ability of antigen to induce a specific immune response.  Immunoreactivity: The ability of antigen to combine with corresponding Ab or sensitized T lymphocyte.  Antigens are either: 1. Soluble in the body fluids. 2. Attached to other particles (cells). Other Characteristics of Ag  The chemical nature of Ag could be proteins, polysaccharides, Lipids and nucleic acid, Complex (lipoprotein, lipopolysaccharide) or Others = small inorganic chemicals.  Each antigen molecule has a set of epitopes (antigenic determinants). Epitope (antigenic determinants) : The part of antigen molecule to which the antibody (or T cell receptor) binds. Antigens usually have many determinants.  Each epitope is recognized by a single antibody according to the different molecular shapes.  Each antigen molecule results in a polyclonal immune response.  A homogenous antibodies population that Interact with a particular epitope on the antigen ( usually Produced by the same clone of plasma B cells) is called Monoclonal antibodies. Paratope It is combining area of the antibody molecule, corresponding to the epitope. Epitope and paratope determine specificity which is hallmark of immunological reaction. Bacteria/virus may contain antigen mosaic (different epitopes) while same epitope on different antigen may present causing antigenic cross reaction. Specific antigen determinants on paratope are called IDIOTOPES.  Immunogen And Hapten : Immunogen is a molecule that can induce detectable immune response (complete antigen). Usually have high molecular weight. Hapten is a molecule that can't induce detectable immune response (incomplete antigen).  Usually has low molecular weight.  Has to be conjugate to other molecules called carrier which are usually protein (albumin) but can be polysaccharide.  Examples : Simple chemicals and drugs = penicillin, aspirin, cosmetic, neomycin skin ointment.  Adjuvant Is a substance that enhances the immunogenicity of an antigen. Mechanisms of adjuvant:  Change the chemical & physical characteristic of Ag.  Improves the Ag process and presentation ability of macrophages.  Stimulate proliferation of lymphocytes. Most adjuvants work by keeping the antigen in the area and by increasing the number of cells involved in the immune response. − Common adjuvant: Incomplete Freund’s adjuvant Complete Freund’s adjuvant Factors Affecting Immunogenicity 1. Foreignness: Ag must be foreign (non-self) to recipient host to induce immune response. 2. Chemical complexity: e.g. Proteins are more antigenic than lipids. 3. Molecular Weight: It must be large to be processed. 4. Host factors: genetic, age, gender, hormonal balance …etc. 5. Dose of antigen: Each antigen has an optimum dose if the dose is significantly lower or higher than the optimum this results in tolerance (unresponsiveness to antigen). 6. Root of administration: Oral, IV, IM ,subcutaneous. Types of antigens Two types of antigens according to their recognition by B-cells: 1. T-dependent Antigens. 2. T-independent Antigens.  Two types according to the source of antigens: 3) Exogenous Antigens. 4) Endogenous Antigens. T-dependent Ag.  Require participation of T- cell (TH-2) to induce humoral immune response.  Mostly are proteins.  Result in antibody class switching in secondary Ab response.  There are B &T memory cells.  e.g. most pathogens. T-independent Ag.  They Don’t Require participation of T- cell to induce humoral immune response.  They have ability to directly stimulate the B – cell.  Mostly are large polysaccharide and lipid molecules.  Produce only IgM antibody response.  No class-switching. No memory cells.  e.g. Lipopolysaccharides of gram negative bacteria & bacterial nucleic acid. Exogenous Antigens A. Bacterial antigens. B. Viral antigens. C. Parasitic antigens. Endogenous antigens A. Human tissue antigens. B. Blood group antigens: A, B and Rh antigens. C. Major histocompatibility complex antigens (MHC). Super antigens (SAgs) Are a class of antigens which cause non -specific activation of T- cells (Potent T cell Mitogen trigger mitosis of CD4+ cells in the absence of Ag processing) resulting in polyclonal T cell activation and massive cytokine release.  The massive T-cell activation and release of large amounts of cytokines cause systemic toxicity.  This method of stimulation is not specific for the pathogen. (it does not lead to acquired immunity) i.e. no memory. e.g. Bacterial toxins as SAgs: Toxic Shock Syndrome Toxin (TSST). Relationship of Antigens to the Host 1. Autoantigens are those that belong to the host; 2. Alloantigens are from the same species as the host but are not identical to the host; 3. heteroantigens are from other species. Heterophile antigens exist in unrelated species, but their structure is so similar that antibody formed to one will cross- react with antigen from a different species. Antigen-presenting cells Are heterogeneous population of leukocytes. Found primary in the skin, lymph nodes, thymus and within mucosal epithelia. 1. Macrophages. 2. B cell. 3. Dendritic cells. Macrophages The mononuclear phagocytic system consists of monocytes circulating in the blood and macrophages in the tissues. The monocyte is considered a leukocyte in transit through the blood, which becomes a macrophage when fixed in a tissue. Monocytes and macrophages as well as granulocytes are able to ingest particulate matter (microorganisms, cells, inert particles) and for this reason are said to have phagocytic functions. Macrophage-like cells serve different functions in different tissues and are named according to their tissue location. Examples include: alveolar macrophages in the lung, histiocytes in connective tissues, Kupffer cells in the liver, mesangial cells in the kidney, microglial cells in the brain, and osteoclasts in the bone. Functions of macrophages Macrophages perform three main functions: 1. phagocytosis, 2. antigen presentation, and 3. cytokine production. Dendritic cells Dendritic cells are so named because of their many long, narrow processes that resemble neuronal dendrites, which make them very efficient at making contacts with foreign materials. They are primarily present in the skin (e.g., Langerhans cells) and the mucosa, from where they migrate to local lymph nodes for presentation of antigen to helper T cells. Types of dendritic cells Four types of dendritic cells are known: 1. Langerhans cells, 2. interstitial dendritic cells, 3. myeloid cells, and 4. Lymphoid dendritic cells. Antigen presenting cells All these cells constitutively express high levels of both class II MHC molecules and members of the costimulatory B7 family. Following microbial invasion or during inflammation, mature and immature forms of Langerhans cells and interstitial dendritic cells migrate into draining lymph nodes, where they make the critical presentation of antigen to TH cells, which is required for the initiation of responses by those key cells. Presents the epitope in the groove of MHC class I or class II on their surface for CD8 &CD4 respectively in association with B7 molecule.