Immunology-introduction Immune system • One of basic homeostatic mechanisms of the body. • Its function is the recognition of foreign/dangerous substances. • The dangerous substances trigger complex reactions which result in elimination of those substances. Immune system • Recognizes foreign/dangerous substances from the environment (mainly microbes) • Is involved in elimination of old and damaged cells of the body. • Attacks tumor and virus-infected cells. Functions of the immune system • Deffence • Autotolerance • Immune surveillance Antigen • Substance, that is recognised by the immune system as a foreign and triggers immune reaction (immunogenicity). • Products of the immune reaction (antibodies, T-lymphocytes) react with the antigen. Requirements of immunogenicity • Foreign (unknown) for the immune system • High molecular weight (> 6 kDa) • Chemical complexity Antigen – functional components • Carrier part of the molecule • Antigenic determinant- epitope (cca 5-7 aminoacids) Antigen - epitopes, carrier part Antigen - epitopes, carrier part Antigen and epitope Chemical composition of antigents • Proteins – usually very good antigens. • Polysacharides- usually only as a part of glycoproteins. • Nucleic acids- poor antigenicity, limited to complexes with proteins • Lipids – only exceptionally, best known are sfingolipids. Protective and nonprotective antigens • Protective antigens – elicit protective immune response that leads to elimination of the microbe. • Non-protective antigens – elicit nonprotective immune response, but it does not lead to elimination of the microbe (e.g. antibodies against HIV). Hapten • Low-molecular weight substances that trigger immune reaction after binding to various proteins of the body. • They react with products of the immune reaction. • Typical examples are metals (Cr, Ni) that trigger type IV immunopathological reactions. Drugs (antibiotics, local anestetics) cause type I immunopathological reaction. Immunogenicity of hapten Cross reactivity of antigens • Products of the immune reaction may, in some conditions, react with substances that are very different from the initial immunogen. • Immunological cross-reactivity not necessary mean similar chemical composition. • The degree of cross reactivity may be different. • Cross reactivity is important in pathogenesis of several autoimmune diseases. Cross reactivity of anntigens High affinity Low affinity Ab1 Ag2 Ab1 Ag1 Adjuvants • Substances, that when mixed with antigen, nonspecifically enhance immune reaction against the antigen. • Freud´s adjuvant: killed Mycobacterium tuberculosis + water-in-oil emulsion. Used in veterinary medicine. • Alum precipitate - AL(OH)3 - used in human medicine. • Mechanisms: improved presentaion of the antigen, fixation of the antigen in the place of application.. Two branches of the immune response • Innate, nonspecific – very quickly recognizes most foreign substances and eliminates them. There is no memory. • Adaptive, specific – high degree of specificity in distinction between self and non-self. The reaction requires several days to be effectively triggered. There is immune memory. Cells of the immune system • Main cells of the immune system – Lymfocytes (T a B) • Accessory cells of the immune system – Granulocytes – Monocytes – Tissue macrophages – Mast cells – Dendritic cells – NK cells – Endotelial cells – Thrombocytes, erythrocytes, fibroblasts, epitelial cells Majority of immune system cell originate in bone marrow Roitt/Broskoff/Male: IMMUNOLOGy, 4th ed Differentiation of cells during hematopoiesis Differentiation of haematopoetic stem cell is influenced by the local environment Lymphocyte – central cell of the immune system Auxiliary cells of the immune system Antigen- presenting cells Organs of the immune system Thymus Primary lymphloid organs Secondary lymphloid organs Bone marrow Waldeyer´s ring (lymphs nodes, tonsilis adenoids Bronchus-associated lymphoid tissue Lymph nodes Bone marrow Spleen Payer´s patch Mesenteric lymph nodes Lamina propria Urogenital lymphoid tissue Lymph nodes Lymph node Roitt/Broskoff/Male: IMMUNOLOGy, 4th ed The Spleen Payer ´s Patches High endotelial venules • Specialized venules. The site where lymphpocytes leave the blood stream and migrate into lymph nodes, spleen, organs of MALT. • Adhesion molecules enable selective attachment of various types of lymphocytes. Circulation of Lymphocytes in the body The role of High Endotelial Venules Roitt/Broskoff/Male: IMMUNOLOGy, 4th ed