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

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

Defenses Against Infection – 1. Surface barriers: skin, conjunctiva, mucous membranes mechanical removal: shedding, tears, mucus, ciliary action, coughing, salivation, swallowing, urination, defecation normal bacterial flora chemical inhibitors: gastric acid, lactic acid, fatty acids,bile salts.. antimicrobial substances: lysozym, secretory IgA

Defenses Against Infection – 2. Nonspecific resistance factors fever, interferon, complement, lysozyme, C-reactive protein, lactoferrin, α1- antitrypsin Inflammation- soluble factors clotting system –Hageman fc. (XII) complement system: chemotactic fc, anaphylatoxins kinin system: bradykinin Inflammation- phagocytes circulating: neutrophils, eosinophils, monocytes, macrophages fixed: alveoli, spleen, liver, bone marow C-reactive protein reacts with bact surface polysaccharides and activates complement lactoferrin – bindsand removes iron as a bacterial nutrient α1- antitrypsin inhibits bacterial enzymes

Defenses Against Infection – 3. Immune response humoral: B-cells, plasma cells, immunoglobulins cell-mediated: T-cells, lymphokins C-reactive protein reacts with bact surface polysaccharides and activates complement lactoferrin – bindsand removes iron as a bacterial nutrient α1- antitrypsin inhibits bacterial enzymes

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

Bacteriemia transient presence of microbes in the bloodstream

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

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

Pyemia presence of infected thrombemboli bearing virulent microbes in the bloodstream

Toxemia presence of microbial toxin (s) without the microbes themselves in the bloodstream staphylococcus enterotoxin, botulotoxin

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

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

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

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

Host Inflammation Immune status General Natural defenses leucocytes macrophages -phagocytosis Immune status immunity (or lack of it) active, passive immunisation, contact lymphocytes immunoglobulins complement 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

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

INFECTION versus DISEASE Pathogenicity (virulence) Incubation Period Carrier State

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

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

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

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 nemají jádro a erg psynt na ribosomech většina extracel, mykobakt obojí, chlam, mykopl, rickettsie oblig intracel AFB acid fast bacilli – stressed due to incidence tb & leprosy

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

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

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…)

Infectious Agents of Humans Parasites -3 Insecta, Arachnida multicellular both DNA and RNA extracellular (Sarcoptes scabiei, fleas, ticks, lice……) svrab = scab strup = rovněž scab, crust