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Aims • Characterize antigens and immunogens • Describe the activation of the complement cascade. • Readings: Abbas & Lichtman, Chapters 3 & 8 Antigens vs. Immunogens • Antigen • Can bind to mediators of the immune response such as antibodies or T cell receptors. • Immunogen • Can initiate an immune response. • “All immunogens are antigens, but not all antigens are immunogens” Adjuvant • Substance administered with an immunogen that enhances the immune response against the immunogen. • Depot effect • Increase inflammatory mediators • Alum (Aluminum hydroxide or aluminum phosphate) • Causes protein immunogens to precipitate. What makes a Good Immunogen? • • • • Large proteins Large glycoproteins Large polysaccharides Large nucleic acids What makes a Poor Immunogen? • • • • • Phospholipids Glycolipids Lipids Small carbohydrates Small polypeptides Physical Nature of Immunogens • Charge - - - - - + + + + - ~ + + + + • little or no influence on immunogenicity. Physical Nature of Immunogens • Shape ~ • little or no influence on immunogenicity. Physical Nature of Immunogens • Size > • Directly proportional to immunogenicity Haptens Small, nonimmunogenic molecule Chemical conjugation “carrier” Large immunogenic molecule (usually protein) Immune response now directed towards otherwise nonimmunogenic molecule Epitopes • Antigenic determinants • Numerous • Unique Immunogens seen Differently by B & T Cells B cell T cell Physical Nature of Immunogens • Complexity > • Directly proportional to immunogenicity Epitopes • One epitope – Hapten • Many identical epitopes – Carbohydrate polymers • Many different epitopes – Proteins Antigens and Immunogens. • Other factors • Genetics Antigens and Immunogens. • Other factors • Foreignness • Does the immune system encounter the antigen normally in the body. (Self) • Is the antigen not normally encountered by the immune system in the body. (Foreign) Antigens and Immunogens. • Other factors • Immunization protocol • Route of administration • Dose of immunogen • Use of adjuvants • Timing and number of administrations Antigens and Immunogens. • Other factors • Persistence of the antigen Antigens and Immunogens. • Other factors • • • • Age Nutritional status Stress Overall health Immunological Cross-reactivity What is a Mitogen? • Any substance which non-specifically activates lymphocytes resulting in the production of products such as antibodies (B lymphocytes) or cytokines (T lymphocytes). The Complement System • Overview – Several protein/glycoprotein factors found in inactive “zymogen” forms in serum • 10% of all serum proteins are part of the complement cascade • Produced by liver and monocytes and macrophages – Relatively unstable and readily cleaved into smaller active molecules • “b” larger subunits bind to membranes • “a” smaller subunits that have biological activity Complement Cascade Functions • Opsonization (prepare food) – Tagging of particles and microorganisms for removal by immune system cells that have Complement receptors – Removal of IC (Ag-Ab linked complexes) – Enhancement of B cell activation Antibody-antigen complex Complement Cascade Functions • Opsonization and Phagocytosis C3 undergoes spontaneous cleavage to form C3a & C3b with C3b binding the microbes and Antibody/Antigen complexes and C3a acting as a chemoattractant –C3b (strong) and C4b (weak) Adapted from Abbas and Lichtman’s Basic Immunology 8-7 Complement Cascade Functions • Recruitment and activation of phagocytic and inflammatory cells to the site of Complement activation – Mast cell activation. • Anaphylatoxins (C5a > C3a >C4a) Histamine Mast cell Complement Cascade Functions • Recruitment and activation of phagocytic and inflammatory cells to the site of Complement activation – Mast cell activation. • Anaphylatoxins (C5a > C3a >C4a) Mast cell Complement Cascade Functions • Chemoattractant and Activator of leukocytes (C5a>C3a>C4a). EC Complement Cascade Functions • Chemoattractant and Activator of leukocytes (C5a>C3a>C4a). Abbas and Lichtman’s Basic Immunology 8-7 Complement Cascade Functions • Formation of the MAC – Ultimate goal of the Complement System is to form the membrane attack complex (MAC) which results in cell lysis. Viron Complement Cascade Functions • Formation of the MAC – Ultimate goal of the Complement System is to form the membrane attack complex (MAC) which results in cell lysis. Adapted from Abbas and Lichtman’s Basic Immunology 8-7 Complement Cascade Functions • Regulation of vascular tone (C2a and C2 kinin, C5a) – Vasodilation – Edema Complement Cascade Functions • Removal of immune complexes – Cleared from plasma by erythrocytes – Removed by phagocytes in liver and spleen EC RBC Antibody-antigen complex Complement Cascade Functions • Removal of immune complexes – Cleared from plasma by erythrocytes – Removed by phagocytes in liver and spleen EC RBC Antibody-antigen complex Complement Cascade Functions • Removal of immune complexes – Cleared from plasma by erythrocytes – Removed by phagocytes in liver and spleen EC RBC Antibody-antigen complex Next Time • Describe the activation of the complement cascade via: – Classical pathway – Alternative pathway • Explain how activation of the complement cascade can impact other immunologic processes. • Describe clinical implications of complement deficiencies. • Readings: Abbas & Lichtman, Chapter 8 Objectives 1. Describe the characteristics of immunogens and antigens. 1. Good vs. bad, physical characteristics, epitopes, cross reactivity. 2. Describe the components and functions of the complement system and cascade.