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General Pathology Basic Principles of Cellular and Organ Pathology Infection – II & Autoimmune Diseases http://www1.lf1.cuni.cz/~jdusk/ Jaroslava Dušková Inst. Pathol. ,1st Med. Faculty, Charles Univ. Prague Inflammation - causes nonliving physical chemical living prions (?) viral bacterial mycotic parasitic AUTOIMMUNE Infectious Agents of Humans Viruses virion obligate intracellular either DNA (adeno, herpes, pox, cytomegalo, EB, papova, HPV, .. or RNA (picorna - entero, polio, coxsackie arbo, rhino, arbo, myxo, paramyxo, RS, rubeola, rabdo, retro,) Virion capsid helical symmetry icosaedral symmetry genome DNA RNA Host General Microorganism Encounter & Successful transmission defenses Site of attack Inflammation Number of microorg. Immune status Pathogenicity Natural Host General – age, race, nutrition, other diseases (diabetes) Natural defenses – skin, mucose integrity – mucus, cilliary action, unobstructed flow – protective secretion (lysosym in tears, gastric acid, IgA Inflammation – leucocytes – macrophages phagocytosis Immune status – immunity (or lack of it) active, passive immunisation, contact – lymphocytes – immunoglobulins – complement Microorganism Successful transmission Site of attack Number of microorg. Pathogenicity invasiveness toxin production multiplication resistence to host defence mechanisms ability to cause necrosis enzyme release Virus – Host Cell Interaction cytocidal stabilised (steady– state) transformation – ONCOGENS Virus-Induced Injury cell entering - surface ligands – viral tropism translocation of the entire virus fusion of the viral envelope with the cell membrane receptor mediated endocytosis intracellular replicative phase – forming of virions using virus specific enzymes virus assembly & release extracellular phase Virus – Organism Interaction infected cell lysis by antibody and complement cell mediated immunity lymphocytes macrophages interferon Virus-Induced Injury Host cell responses: DNA, RNA and protein synthesis metabolic derangements cell lysis / cell fusion multinuclear formation viral inclusions Infectious Agents of Humans Viruses virion obligate intracellular either DNA (adeno, herpes, pox, cytomegalo, EB, papova, HPV, .. or RNA (picorna – entero, polio, coxsackie arbo, rhino, arbo, myxo, paramyxo, RS, rubeola, rabdo, retro,) Inflammation Definition: complex reaction of organism to damage (aim: homeostasis maintenance) Inflammation - Causes nonliving physical chemical living viral bacterial mycotic parasitic AUTOIMMUNE Inflammation – immunity Nonspecific antibodies imunocomplexes on dendritic cells long lasting antigen presentation Mechanisms of Immune Response antigen specific humoral B– lymphocytes cellular T– lymphocytes INTERACTION B-lympho–Th – affinity maturation – plasmocyte Autoimmunity Def.: lack of self-tolerance Autoimmunity constant activity in organogenesis regeneration metalaxia Autoimmune Diseases loss of self-tolerance resulting into damage of organ /tissue Mechanisms Preventing Antiself Reactivity: clonal deletion (thymus) clonal anergy (thymus) peripheral clonal supression by Tsupressor cells ( B,T helpers) Inflammation – autoimmune Systemic autoimmune diseases DISEASE SLE RA Sjögren dis. Syst. sclerodermia Dermato–polymyositis Prim. vasc. syndromes ANTIBODY ANA, ENA collag. II, Fc –Ig (rheum. factor) ANA,ENA ENA (Scl–70) ENA (Jo–1) ANCA Inflammation – autoimmune Organ autoimmune diseases – skin ANTIBODY DISEASE intercel. epit. matrix pemphigus basal membrane of epidermis pemphigoid Inflammation – autoimmune Organ autoimmune diseases – endocrine ANTIBODY DISEASE TGB, microsomes pancreas cells insulin ins. receptors adrenal microsomes TSH rec. GB, HT DM I I–res. DM I–res. DM Adison dis. GB Inflammation – autoimmune Organ autoimmune diseases – GIT ANTIBODY DISEASE mitochondrie prim. bill. cirrhosis membr. hct., cytosol CAH gliadin gluten enteropathy Inflammation – autoimmune Organ autoimmune diseases – CNS ANTIBODY DISEASE acetylcholin rec. myasthenia gravis disseminated sclerosis basic myelin protein