1. General Pathology Basic Principles of Cellular and Organ Pathology Infection - I Jaroslava Dušková Inst. Pathol.,1st Med. Faculty, Charles Univ. Prague http://www1.lf1.cuni.cz/~jdusk/

2. Inflammation - causes v nonliving physical chemical v living prions (?) viral bacterial mycotic parasitic AUTOIMMUNE

3. Interaction of Organism and Microorganism – Terms v Bacteriemia (transient) v Sepsis/ Septicemia v Pyemia v Toxemia v Viremia

4. Bacteriemia v transient presence of microbes in the bloodstream

5. Sepsis / Septicemia (Severe Bacteremia) u increasing numbers of microbes (& their toxins) in the bloodstream

6. Sepsis/Septicemia Def. systemic response to infection manifestating as v tachypnoe > 20/min. v tachycardia > 90/min. v temperature > 39 st. C. (ev. < 36st.C) v leucocytosis > 15 000/1  l (ev. < 4000/1  l)

7. Sepsis – Pathogenetic Factors v Endotoxin, toxins G+ v Macrophages v Cytokins v NO v PAF (Platelets Activating Factor) TNF, IL–1 TNF, IL–1, IL–6 NO synthesis vasodilation coagulation

8. Syndrome of Systemic Inflammatory Response Def. systemic response to an AGENT manifestating as v tachypnoe > 20/min. v tachycardia > 90/min. v temperature > 39 st. C. (ev. < 36st.C) v leucocytosis > 15 000/1  l (ev. < 4000/1  l) AGENT : pancreatitis, injury, burns…..

9. Pyemia u presence of infected thrombemboli bearing virulent microbes in the bloodstream

10. Toxemia u presence of microbial toxin (s) without the microbes themselves in the bloodstream

11. Endotoxin u lipopolysaccharide component of G- bacteria outer wall u effects: fever, shock, DIC, RDS u effects mediated by IL-1, TNF

12. Exotoxins -1 u often enzymes (leukocidins, hemolysins, hyaluronidases, coagulases, fibrinolysins) u others………….

13. Exotoxins -2 u diphteria toxin – inhibition of cellular proteosynthesis u botulotoxin – block of the cholinergic transmission u choleratoxin – increase in cAMP, losses of isoosmotic fluid via enterocytes

14. 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

15. 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

16. 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

17. INFECTION versus DISEASE v Pathogenicity (virulence) v Incubation Period v Carrier State

18. Agent – Host Interaction v cytocidal v stabilised (steady– state) v transformation – ONCOGENS

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

20. Inflammation - causes v non infectious physical chemical v infectious prions viral bacterial mycotic parasitic AUTOIMMUNE

21. Infectious Agents of Humans u prions u viruses (DNA, RNA) u bacteria (incl. chlamydia, mycoplasma, rickettsia – obligatory intracellular parasites) u fungi (yeasts, molds) u parasites (protozoa, helmints, ectoparasites- insects: lice, mites, ticks; spiders)

22. Infectious Agents of Humans Bacteria  simple cells – prokaryotes  both DNA and RNA  cocci, bacilli (AFB!), spirochetes….  Gram positive /negative  extra- and/or intracellular  aerobic/ anaerobic

23. Infectious Agents of Humans Fungi  complex cells – eukaryotes  both DNA and RNA  yeasts, molds (hyphae, pseudohyphae…)  PAS, impregnation  extra- or intracellular  mostly opportune pathogens

24. Infectious Agents of Humans Parasites -1 Protozoa  complex cells – eukaryotes  both DNA and RNA  extra- or intracellular (Amebas, Trichomonas,Trypanosoma, Toxoplasma, Plasmodium, Pneumocystis…)

25. Infectious Agents of Humans Parasites -2 Metazoa (helmints and flukes)  multicellular  both DNA and RNA  flat and round worms  extracellular (Taenia, Ascaris, Enterobius, Trichuris Echinococcus, Clonorchis, Schistosoma, Wuchereria…)

27. Infectious Agents of Humans Parasites -3 Insecta, Arachnida  multicellular  both DNA and RNA  extracellular (Sarcoptes scabiei, fleas, ticks, lice……)