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

Bacteriemia (transient) Sepsis/ Septicemia Pyemia Toxemia Viremia

Bacterial toxins & their action Host & microorganism encounter Infection versus disease Infectious agents of humans – part one

bacteria fungi parasites worms insects

Inflammation - causes

nonlivingphysical

chemical

livingprions

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, brain

Defenses Against Infection – 3.

Immune response– humoral: B-cells, plasma cells, immunoglobulins

– cell-mediated: T-cells, lymphokins

Interaction of Organism and Microorganism – Terms

Bacteriemia (transient) Sepsis/ Septicemia Pyemia Toxemia Viremia

Bacteriemia transient presence of

microbes in the bloodstream

Sepsis / Septicemia (Severe Bacteremia)

increasing numbers of microbes (& their toxins) in the bloodstream

Sepsis/SepticemiaDef.

systemic response to infection presenting as

tachypnoe > 20/min. tachycardia > 90/min. temperature > 39 st. C. (ev. < 36st.C) leucocytosis > 15 000/1l (ev. < 4000/1l)

Sepsis – Pathogenetic Factors

Endotoxin, toxins G+ Macrophages Cytokins

NO PAF (Platelets Activating Factor)

TNF, IL–1

TNF, IL–1, IL–6

NO synthesis

vasodilation coagulation

Syndrome of Systemic Inflammatory ResponseDef.

systemic response to an AGENT manifestating as

tachypnoe > 20/min. tachycardia > 90/min. temperature > 39 st. C. (ev. < 36st.C) leucocytosis > 15 000/1l (ev. < 4000/1l)

AGENT : pancreatitis, injury, burns…..

Pyemia presence of infected thrombemboli bearing virulent microbes in the bloodstream

Endocarditis bacterialis acuta

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

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 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

INFECTION versus DISEASE

Pathogenicity (virulence) Incubation Period Carrier State

Agent – Host Interaction

cytocidal stabilised (steady– state) transformation –

ONCOGENS

Inflammation - causes

non infectious

physical

chemical

infectiousprions

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

G+ cocci Staphylococcus aureus Staphylococcus epidermidis Staphylococcus

saprophyticus

Streptococcus α-hemolyticus Streptococcus β-hemolyticus

Skin: impetigo, furunculus, carbunculus, panaritium,

hidradenitis mastitis osteomyelitis pharyngitis enterotoxicosis

impetigo tonsilitis, angina scarlet fever erysipelas (St. Anthony´fire)

complications: rheumatic fever, glomerulonephritis

G+ rods non-spore forming aerobes

– Corynebacterium diphteriae– Listeria monocytogenes – Erysipelothrix rhusiopathiae

spore forming aerobes– Bacillus anthracis

Diphteria Listeriosis Erysipeloid

Anthrax

G- rods Bordetella pertusis Pseudomonas aeruginosa Legionella pneumophilla Brucella abortus, Francisella

tularemiae, Campylobacter Helicobacter pylori Escherichia coli Klebsiella pneumoniae Salmonella typhi Shigella dysenteriae Vibrio cholerae Haemophillus influenzae,

Ducreyi

Pertussis respir and urinary inf. pneumonia granulomatous, typhoid,

pneumonia gastritis, ulcers, tumours urinary inf. pneumonia typhoid fever dysenteria cholera pneumonia, ulcus molle

G- Cocci

Neisseria gonorrhoeae Neisseria meningitidis

Gonorrhoea Meningitis

Anaerobic bacteria

non-spore forming anaerobs– Actinomyces israeli G+– Fusobacterium G-

spore forming anaerobs– Clostridium tetani– Clostridium botulinum– Clostridium perfringens,

septicum, histolyticum– Clostridium difficile

Actinomycosis cellulitis

Tetanus Botulismus Gangrene 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 -1Protozoa complex cells – eukaryotes both DNA and RNA extra- or intracellular

(Amebas, Trichomonas,Trypanosoma, Toxoplasma, Plasmodium, Pneumocystis…)

Infectious Agents of Humans Parasites -2Metazoa (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 -3Insecta, Arachnida multicellular both DNA and RNA extracellular

(Sarcoptes scabiei, fleas, ticks, lice……)

The tick-borne diseases

Babesiosis (a malaria-like infection Babesia microti) Ehrlichiosis (rickettsia Ehrlichia canis) Lyme disease (Borelia Burgdorferi) Rocky Mountain spotted fever (Rickettsia rickettsi)

Tularemia (rabbit fever Francisella tularensis ) Tick paralysis (virus a member of the family Flaviviridae)