Antigen & Immunogen PDF

Immunogens or Antigens Dr. Reem Abdelrahman Lecturer of microbiology and immunology Faculty of medicine Helwan university  continued Define immunogen, antigen , epitope, paratope and hapten....

Immunogens or Antigens Dr. Reem Abdelrahman Lecturer of microbiology and immunology Faculty of medicine Helwan university  continued Define immunogen, antigen , epitope, paratope and hapten. Objectives Recognize factors influencing immunogenicity. Identify forms of antigen antibody binding. Define heterophile antigen and antibody. Enumerate laboratory tests based on heterophile antigen. Recognize types of antigens. Recognize binding and recognition molecules in immune system. Antigen: Immunogens are any foreign substances which can stimulate a specific immune response (humoral or cell mediated immunity). Antigens have the ability to combine specifically with the antibodies produced or sensitized T lymphocytes induced. However, the two words, antigen and immunogen, are used almost interchangeably. Epitope: The small parts of the foreign molecule that can stimulate production of or bind to antibody. These parts are called "epitopes" or antigenic determinants. Each may be composed of 4-7 amino acids, or monosaccharide residues. The number of epitopes on a molecule varies with molecular size. Human albumin has at least 6 different epitopes. Paratope: Paratope also called an antigen-binding site, is a part of an antibody which recognizes and binds to an antigen. Antigen can be complete Incomplete (hapten) Haptens: Haptens (to fasten): These are low molecular weight substances which, by themselves, are not capable of inducing an immune response. However, when coupled or conjugated to a larger carrier protein, the haptens are transformed into antigenic determinants on the carrier molecule and are capable of inducing an immune response, i.e. they become immunogenic. Example of hapten is penicillin small non antigenic molecule when combined with certain serum proteins of sensitive individuals the result molecules become immunogenic, activate lymphocytes and stimulate severe immune response.  Factors affecting immunogenicity Molecular Chemical Host genetic Foreignness degradability Administration size nature factors Dosage Route Adjuvants 1- Foreignness Tolerance Self Autoimmune Immune system Innate immunity Non-self Adaptive immunity For a substance to be immunogenic it must be foreign to the animal in which it is introduced. The immune system of an individual can normally distinguish between body components, i.e. "self and foreign substances "non-self. Normally, the body is tolerant to its own components and does not initiate an immune response against them. Under certain circumstances, however, this auto-tolerance may be disturbed, permitting the individual to react against himself, leading to autoimmune diseases.  2- Molecular size Small molecules such as amino acids or monosaccharides are usually not immunogenic. As a rule, molecules with a molecular weight of less than 5000-10,000, have no or only weak immunogenicity.  3- Chemical nature: The most potent immunogens are proteins. Some polysaccharides of high molecular weight are immunogenic. More complex proteins are more immunogenic i.e. globular proteins are more immunogenic than fibrillar proteins.  4- Degradability: For a substance to be immunogenic it has to be susceptible to partial enzymatic degradation that occurs during antigen processing by presenting cells such as macrophages. It has been found that peptides composed of D-amino acids, which are resistant to enzymatic degradation are not immunogenic, whereas their L-isomers are susceptible to enzymes and are immunogenic. 5- Methods of antigen administration a) dosage b) route c) adjuvants a- Dosage: A state of antigen specific unresponsiveness (immunologic tolerance) can result if very high or very low doses of certain antigens are administered. The number of doses administered also affects the outcome of the immune response. Repeated administration of booster doses are required to stimulate a strong immune response. b- Route of administration: Parenteral routes are preferred to oral routes for experimental immunogens as they induce stronger immune response. I.V. injected antigens are carried to the spleen while subcutaneously injected antigens are carried to the local lymph nodes. Difference in the lymphoid cells that populate these organs may be reflected in the subsequent immune response. c- Adjuvants (to help): These are substances that, when mixed with an antigen before its administration will increase the immune response to that antigen. Aluminum hydroxide is used to enhance the immune response as in the toxoid used for vaccination against diphtheria.  The mechanism of action of adjuvants 1 2 3 4 Macrophage Costimulatory Depot effect activation signals lymphocytes Granuloma around the antigen. Phagocytosis. Maximum Non specific Prolonged immune system Antigen processing. activation of T- stimulation. Cytokine secretion. cells. proliferation.  6- host genetic factors: Different response between individuals: Strong responders. Weak responders. Non-responders. Forms of antigen antibody binding Lock and key situation High affinity Low affinity antibody antibody (poor fit) Antigen Antibody Binding : The binding of antigen to antibody binding site can be likened to a "lock and key" situation. The most efficient immunological responses occur when the antigen and antibody fit exactly (high affinity antibody). Antigen Antibody Binding : Sometimes an antigen can combine as a "poor fit" with an antibody (low affinity antibody) that was produced in response to an unrelated or partially related antigen which bears one or more epitopes in common. These are known as heterophile antibodies and heterophile antigens and the phenomenon is known as "cross reactivity". This can be met with in vivo in some infections of autoimmune nature, e.g. in acute rheumatic fever; it is thought that antibodies to Strept. pyogenes M antigen cross react with cardiac muscle proteins leading to rheumatic carditis and valve destruction. Heterophile antigen (cross reactivity) Cross reactivity means the ability of an antibody to react with similar epitopes on different antigens. Cross reactivity 1 2 Antibodies to Cardiac Acute strept pyogen muscle rheumatic M antigen. protein. fever. Laboratory tests based on heterophile antigen  1- Paul Bunnell test Diagnose infectious mononucleosis (Epstein Barr) Virus. Cross 1 2 reactivity Patient’s Sheep RBCs Agglutination. serum (heterophile antibody)  2- Cold agglutinins Patients with mycoplasma pneumonia. Cross reactivity 1 2 Patient’s Human Agglutination. serum group O red (heterophile cells at 4℃. antibody)  3-VDRL and RPR test In sera of syphilitic patients Cross reactivity 1 2 Patient’s Cardiolipin Agglutination. serum antigen. (reagin).  Types of antigens according to source Super Human tissue Bacterial Viral antigens antigens Antigens that activate Blood group Soluble antigens: Protein coat multiple clones of T antigens lymphocytes leading to exotoxins, enzymes viral antigens increased cytokine (A-B-RH) secretion. Attach TCR- MHC Soluble antigens that outside peptide binding Cellular antigens; groove. Histocompatibility diffuse in surrounding capsular , flagellar fluid e.g., soluble Non specific activation antigens nucleoproteins with no memory. MHC (HLA) Glycoprotein molecules present on membranes of tissue cells. They are coded for by MHC genes present on chromosome 6. MHC I MHC II Site All nucleated cells. Antigen presenting cells. (MHC restriction) T cell identification T cytotoxic cells. T helper cells Graft rejection occurs due to immunological response to tissue graft from donor with different HLA type. Antigen binding and recognition molecules of the immune system B-cell receptor T-cell receptor MHC molecules 1- B cell receptors (BCR) which are membrane-bound immunoglobulins (IgM and IgD) on B cells. They can bind unprocessed antigens of almost any chemical composition. 2- T cell receptors (TCR) which are composed of 𝛼 and 𝛽 chains anchored to T cells by their cytoplasmic tail. There is a groove in both chains which binds small peptides presented by MHC molecules on the surface of APCs. 3- MHC molecules are essential for presentation of peptides so that they can be recognized by and bind to TCRs.  Differentiate between immunogen, antigen , epitope, paratope and hapten! What are factors influencing immunogenicity? What are forms of antigen antibody binding?  What is heterophile antigen and antibody? Innumerate types of antigens!