ANTIGENS
Dr, HUDA IBRAHIM Lec.no.3TEACHING OBJECTIVES (one hour) 1. To compare and contrast immunogen, antigen , carrier and hapten 2. To describe the types & properties of an antigens. 3. To understand the recognition of an antigens. 4. To introduce the classification of an antigens.
DEFINITIONS
Immunogen - A substance that induces a specific immune response. Antigen (Ag) - A substance that reacts with the products of a specific immune response. Hapten - A substance that is non-immunogenic but which can react with the products of a specific immune response. Haptens are small molecules which could never induce an immune response when administered by themselves but which can when coupled to a carrier molecule. Epitope or Antigenic Determinant - That portion of an antigen that combines with the products of a specific immune response. Antibody (Ab) - A specific protein which is produced in response to an immunogen and which reacts with an antigen.What can be an Antigen?
Ags can be: Foreign substances like micro organisms & its products, toxins etc. Body’s own proteins, expressed in an inappropriate manner like tumor cells, autoantigens, transfused blood or the cells of transplanted organsProperties of Antigen
2 properties of antigen:Immunogenicity – Induction of immune responseImmunological reactivity - Specific reaction with Abs or with T cells. * Based on these 2 attributes, functional classification of Ags has been made.Recognition of an Antigen
Bacteria or viruses are not Ags by themselves but they contain Ags both on their surface and inside the cell. Ags are recognized by B cells and their surface Igs (sIgM) or the T cell receptor on T cells. The T cells require the protein to be ingested, degraded and presented on the surface of a special cell called Antigen Presenting Cell (APC). The processed Ags are presented along with MHC/ HLA molecules by APCsClassification of Antigens
Based on Immunogenicity (functional classification) Origin of Ag Source of Ag Biological classification
1. Functional Classification
Complete Ag - Able to induce Ab formation. Hence called as IMMUNOGENS. - Produce a specific & observable reaction with the Abs so produced. Haptens / Incomplete Ag - Substances which can not induce Ab formation by themselves but can react specifically with Abs. Hapten + Carrier Complete antigen (Immunogen)2. Origin of Antigens
Ags can be classified on the basis of their origin:Exogenous Ags – from outsideenter the body by inhalation, ingestion or injection. these are taken by the APCs and degraded into small peptides. APCs then present them to helper T cells by using MHC type II molecules.Endogenous Ags – generated within the cell as a result of normal cell metabolism, or because of viral or intracellular pathogenic infection.The fragments are presented along with MHC type I molecules to cytotoxic T cells.Antigen processing & presentation
Exogenous AgsEndogenous Ags
3. Source of an Antigen
Xenoantigen – foreign Ag, from different species e.g. bacteria, virusesAlloantigen – different individual from same species e.g. blood group AgAutoantigen – same individual e.g. lens protein, tumor cellsHeterophile antigen – Common/ related Ags shared by different species e.g. M protein of streptococus bears common antigen determinant with basement membrane of kidney4. Biological Classes of Ags
Depending on the ability to induce Ab formation, Ags are classified as: T cell dependent (TD) ags T cell independent (TI) agsEpitope or Antigenic determinant
Shmallest unit of antigenicity. Small area/ part on the Ag which combines with its complementary site either on the specific Ab or T cell receptor.Interaction between epitopes of different shapes & Ag combining site on the Ab
Determinants of AntigenicityProperties which make a substance antigenic: Size Nature of Ag Foreignness Susceptibility to tissue enzymes. Exposure to the Ag.
1. Size
Large molecules are highly antigenic. Low mol.wt. (<5000) substances are weakly antigenic or non antigenic. Can be made antigenic by absorbing them on large inert particles like bentonite or kaolin.2. Nature of the Ag
Macromolecular proteins are the most potent immunogens. Polysaccharides, glycoproteins, synthetic polypeptides are good immunogens. Nucleic acids are poor immunogen & pure lipids are non-immunogen. Antigenicity can be enhanced by conjugating to a protein.3. Foreignness
Ags which are ‘foreign’ to the individual induce an immune response.Antigenicity is related to the degree of foreignness - Ags from other individuals of the same species are less antigenic than those from other species.4. Susceptibility to tissue enzymes
Substances which are rapidly metabolised & are susceptible to the action of tissue enzymes behave as more potent Ags. Ags are degraded into fragments of appropriate size containing the epitope. Degradation is brought about by phagocytosis & the intracellular enzymes.
5. Exposure to the Ag
Dose of the immunogen : optimum dose * Lower or higher than the optimum can induce tolerance (inability to induce an immune response) Route of administration: subcutaneous is better than I.V or intr-agastric route. Immune response can be increased by mixing the Ag with a powerful adjuvant.Adjuvants
Substances which are added to or emulsified with an Ag so as to enhance the Ab production. Example - Inorganic salts : Aluminum hydroxideSuper antigen
When the immune system encounters a conventional T-dependent Ag , only a small fraction of T cell population is able to recognize the antigen & activated. Some antigens which polyclonally activate a large fraction of T-cells (up to 25%) are superantigen.Examples:Staphylococcal enterotoxins ,Staphylococcal toxic shock toxin , Staph.exfoliating toxins & Streptococcal pyrogenic exotoxins.