General Pathology Basic Principles of Cellular and Organ Pathology Infection - I Jaroslava Dušková Inst. Pathol.,1st Med. Faculty, Charles Univ. Prague

Infection–I – table of contents  Defenses against infection  Interaction of organism and microorganism v Bacteriemia (transient) v Sepsis/ Septicemia v Pyemia v Toxemia v Viremia v Bacterial toxins & their action v Host & microorganism encounter v Infection versus disease v Infectious agents of humans – part one v bacteria v fungi v parasites v worms v insects

Inflammation - causes v nonliving physical chemical v living prions viral bacterial mycotic parasitic AUTOIMMUNE

Defenses Against Infection – 1. u 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. u Nonspecific resistance factors –fever, interferon, complement, lysozyme, C-reactive protein, lactoferrin, α1- antitrypsin u Inflammation- soluble factors –clotting system –Hageman fc. (XII) –complement system: chemotactic fc, anaphylatoxins –kinin system: bradykinin u Inflammation- phagocytes –circulating: neutrophils, eosinophils, monocytes, macrophages –fixed: alveoli, spleen, liver, bone marow, brain

Defenses Against Infection – 3. u Immune response –humoral: B-cells, plasma cells, immunoglobulins –cell-mediated: T-cells, lymphokins

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

Bacteriemia v transient presence of microbes in the bloodstream

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

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

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

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 > /1  l (ev. < 4000/1  l) AGENT : pancreatitis, injury, burns…..

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

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

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

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

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

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

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

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

Inflammation - causes v non infectious physical chemical v infectious prions (non living but transmissible) viral bacterial mycotic parasitic AUTOIMMUNE

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)

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

G+ cocci u Staphylococcus aureus u Staphylococcus epidermidis u Staphylococcus saprophyticus u Streptococcus α-hemolyticus u Streptococcus β-hemolyticus u Skin: impetigo, furunculus, carbunculus, panaritium, u hidradenitis u mastitis u osteomyelitis u pharyngitis u enterotoxicosis u impetigo u tonsilitis, angina u scarlet fever u erysipelas (St. Anthony´fire) complications: rheumatic fever, glomerulonephritis

G+ rods u non-spore forming aerobes –Corynebacterium diphteriae –Listeria monocytogenes –Erysipelothrix rhusiopathiae u spore forming aerobes –Bacillus anthracis u Diphteria u Listeriosis u Erysipeloid u Anthrax

G- rods u Bordetella pertusis u Pseudomonas aeruginosa u Legionella pneumophilla u Brucella abortus, Francisella tularemiae, Campylobacter u Helicobacter pylori u Escherichia coli u Klebsiella pneumoniae u Salmonella typhi u Shigella dysenteriae u Vibrio cholerae u Haemophillus influenzae, Ducreyi u Pertussis u respir and urinary inf. u pneumonia u granulomatous, typhoid, pneumonia u gastritis, ulcers, tumours u urinary inf. u pneumonia u typhoid fever u dysenteria u cholera u pneumonia, ulcus molle

G- Cocci u Neisseria gonorrhoeae u Neisseria meningitidis u Gonorrhoea u Meningitis

Anaerobic bacteria u non-spore forming anaerobs – Actinomyces israeli G+ – Fusobacterium G- u spore forming anaerobs –Clostridium tetani –Clostridium botulinum –Clostridium perfringens, septicum, histolyticum –Clostridium difficile u Actinomycosis u cellulitis u Tetanus u Botulismus u Gangrene u pseudomembranous colitis

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……)

The tick-borne diseases u Babesiosis (a malaria-like infection Babesia microti) u Ehrlichiosis (rickettsia Ehrlichia canis) u Lyme disease (Borelia Burgdorferi) u Rocky Mountain spotted fever (Rickettsia rickettsi) u Tularemia (rabbit fever Francisella tularensis ) u Tick paralysis ( virus a member of the family Flaviviridae)