General Pathology Basic Principles of Cellular and Organ Pathology Infection – II & Autoimmune Diseases Jaroslava Dušková Inst. Pathol.,1st Med. Faculty, Charles Univ. Prague

Inflammation - causes v nonliving physical chemical v 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 v capsid helical symmetry icosaedral symmetry v genome DNA RNA

Host & Microorganism Encounter u General u Natural defenses u Inflammation u Immune status u Successful transmission u Site of attack u Number of microorg. u Pathogenicity

Host u General –age, race, nutrition, other diseases (diabetes) u Natural defenses –skin, mucose integrity –mucus, cilliary action, unobstructed flow –protective secretion (lysosym in tears, gastric acid, IgA u Inflammation –leucocytes –macrophages - phagocytosis u Immune status –immunity (or lack of it) active, passive immunisation, contact –lymphocytes –immunoglobulins –complement

Microorganism u Successful transmission u Site of attack u Number of microorg. u Pathogenicity invasiveness toxin production multiplication resistence to host defence mechanisms ability to cause necrosis enzyme release

Virus – Host Cell Interaction v cytocidal v stabilised (steady– state) v transformation – ONCOGENS

Virus-Induced Injury v cell entering - surface ligands – viral tropism v translocation of the entire virus v fusion of the viral envelope with the cell membrane v receptor mediated endocytosis v intracellular replicative phase – forming of virions using virus specific enzymes v virus assembly & release extracellular phase

Virus – Organism Interaction v infected cell lysis by antibody and complement v cell mediated immunity lymphocytes macrophages interferon 

Virus-Induced Injury Host cell responses: u DNA, RNA and protein synthesis u metabolic derangements u cell lysis / cell fusion u multinuclear formation u 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 v nonliving physical chemical v living viral bacterial mycotic parasitic AUTOIMMUNE

Inflammation – immunity Nonspecific antibodies v imunocomplexes on dendritic cells v long lasting antigen presentation

v antigen specific v humoral B– lymphocytes v cellular T– lymphocytes INTERACTION B-lympho–T h – affinity maturation – plasmocyte Mechanisms of Immune Response

Autoimmunity Def.: lack of self-tolerance

Autoimmunity constant activity in v organogenesis v regeneration v metalaxia

Autoimmune Diseases loss of self-tolerance resulting into damage of organ /tissue

Mechanisms Preventing Antiself Reactivity: u clonal deletion (thymus) u clonal anergy (thymus) u peripheral clonal supression by T supressor 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, F c –Ig (rheum. factor) ANA,ENA ENA (Scl–70) ENA (Jo–1) ANCA

Inflammation – autoimmune Organ autoimmune diseases – skin ANTIBODY intercel. epit. matrix basal membraneof epidermis DISEASE pemphigus pemphigoid

Inflammation – autoimmune Organ autoimmune diseases – endocrine ANTIBODY TGB, microsomes pancreas  cells insulin ins. receptors adrenal microsomes TSH rec. DISEASE GB, HT DM I I–res. DM Adison dis. GB

Inflammation – autoimmune Organ autoimmune diseases – GIT ANTIBODY mitochondrie membr. hct., cytosol gliadin DISEASE prim. bill. cirrhosis CAH gluten enteropathy

Inflammation – autoimmune Organ autoimmune diseases – CNS ANTIBODY acetylcholin rec. basic myelin protein DISEASE myasthenia gravis disseminated sclerosis