Institute for Microbiology, Medical Faculty of Masaryk University and St. Anna Faculty Hospital in Brno Miroslav Votava PATHOGENESIS OF INFECTION – I The 8th lecture for 2nd-year students April 13th , 2015 Three elements of pathogenicity and virulence – revision •1. Communicability (transmissibility) = ability to be transmitted between hosts •2. Invasiveness = ability to: • - enter the host ability to • - multiply within = overcome • - spread through it the defence •3. Toxicity = ability to do harm to the host How do microbes face immunity A – revision •A) Ability to overcome the innate immunity: • •- Resisting complement inhibiting complement activation protecting their own surface •- Resisting phagocytosis avoiding being engulfed (capsule!) surviving inside the phagocyte •- Interfering with the cytokine function How do microbes face immunity B – revision •B) Ability to overcome the acquired immunity: •Always an attempt to avoid antibodies or immune lymphocytes by •1) quick reproduction (respiratory viruses, diarrhoeal agents, malarial plasmodia) •2) attempting to deceive immune system to hide to change one‘s own antigens to induce tolerance •3) attempting to suppress immune reaction • Toxicity I – revision •Damage by direct effect of infectious agent •Cellular death lysis by toxins, viruses, immune lymphocytes apoptosis (HSV, shigellae) •Metabolic injury – influence of exotoxins •Mechanical causes (schistosomal eggs, P. jirovecii, pseudomembranes in diphtheria) •The most frequent cause of death in bacterial infections → septic shock triggered by endotoxins G – : lipopolysaccharide G + : teichoic acid + peptidoglycan • Toxicity II – revision •Damage as a result of defence reactions – a) • •a) Injuries caused by inflammatory reaction: calor, rubor, tumor, dolor, functio laesa = typical markers of inflammation = symptoms of disease • edema: encephalitis, epiglottitis inflammatory infiltrate: pneumonia suppuration: blennorrhoea neonatorum formation of connective tissue: scarring • Toxicity III – revision •Damage as a result of defence reactions – b) • •b) Injuries caused by specific immune reaction (immunopathological consequences of hypersensitivity) •1st type: (IgE, anaphylaxis) helminthoses •2nd type: (cytotoxicity) hepatitis B, febris rheumat. •3rd type: (immunocomplexes) farmers lungs, poststreptococcal nephritis, systemic reactions during sepsis •4th type: (late, cellular) tbc, lepra, syphilis, actinomycosis, rash in measles • What is the pathogenesis? •Pathogenesis explains the origin and development of pathological symptoms •What does the pathogenesis of infection include? 1.The way the agent spreads through the macroorganism 2.Mechanisms of defence against it 3.Actual causes of symptoms: • a) either the infectious agent itself, • b) or the reaction of macroorganism to it Spread of the agent through the macroorganism •→ portal of entry (skin, mucosae, placenta) •→ sites of primary multiplication: portal of entry vicinity (= primary affect) regional lymphatic nodes (+ primary affect = primary complex) •→ actual spread (dissemination of agent): by means of lymph, blood, per continuitatem, along nerves •→ target organ: typically in viral diseases •→ sites of elimination from macroorganism: may not be the same as portal of entry PORTALS OF the infectious agent’s ENTRY •Mucosae • respiratory ways and lungs • alimentary tract • urogenital tract • conjunctiva and cornea •Skin and hypodermis •Placenta Respiratory tract mucosa – I •NOSE + NASOPHARYNX: respiratory viruses (rhinoviruses, coronaviruses, adenov.), HSV, viruses of exanthematic infections (measles, rubella, chickenpox), amoebae (Naegleria , Acantamoeba, Balamuthia) •Secondary bacterial agents: Haemophilus influenzae b, Strept. pneumoniae, Staph. aureus, Moraxella catarrhalis – the gang of 4 •Chronic infections: ditto + Klebs. pneumoniae ssp. ozaenae, Kl. pn. ssp. rhinoscleromatis Respiratory tract mucosa – II •TONSILS + PHARYNX: respiratory viruses, HSV, Epstein-Barr v., coxsackieviruses A; Streptococcus pyogenes, other β-hemolytic streptococci, S. pneumoniae, S. aureus, H. influenzae serotype b, Neisseria meningitidis, N. gonorrhoeae, Arcanobacterium haemolyticum, Corynebacterium diphtheriae; Candida albicans; Toxoplasma gondii •EPIGLOTTIS: Haemophilus influenzae type b • Respiratory tract mucosa – III •LARYNX + TRACHEA: parainfluenza viruses, influenza viruses, RSV, adenoviruses; Chlamydia pneumoniae, Mycoplasma pneumoniae, Corynebacterium diphtheriae •Secondarily: S. aureus, H. influenzae •BRONCHI: influenza v., adenoviruses, RSV, parainfluenza v., RSV; M. pneumoniae, Ch. pneumoniae, Bordetella pertussis •Sec.: S. pneumoniae, H. influenzae type b, Staph. aureus, Moraxella catarrhalis •BRONCHIOLES: RSV • Lungs •BRONCHOPNEUMONIA (alveoli & bronchi): Str. pneumoniae, Staph. aureus, H. influenzae type b; Legionella pneumophila, Klebsiella pneumoniae, E. coli, Pseudomonas aeruginosa; Francisella tularensis, Yersinia pestis •ATYPICAL PNEUMONIA (intersticium): Mycopl. pneumoniae, influenza virus A, Ch. pneumoniae; Chlamydia psittaci (ornithosis), Coxiella burnetii (Q fever); Pneumocystis jirovecii, CMV, atypical mycobacteria, Nocardia asteroides •SUBACUTE & CHRONIC PNEUMONIA: - anaerobes (Bacteroides fragilis, Prevotella, Peptostreptococcus) - Mycobacterium tuberculosis Gastrointestinal tract mucosa •ORAL CAVITY: HSV, Candida albicans •OESOPHAGUS: CMV, C. albicans •STOMACH: Helicobacter pylori •SMALL INTESTINE: Campylobacter jejuni, salmonellae (incl. Salmonella Typhi), ETEC, EPEC etc., Yersinia enterocolitica, Vibrio cholerae; enteroviruses (polio!), rotaviruses, noroviruses; Giardia lamblia, Cryptosporidium parvum; tapeworms, pinworms, roundworms, flukes etc. •LARGE INTESTINE + RECTUM: Shigella sonnei (bacterial dysentery), Entamoeba histolytica (amoebic dysentery) Urogenital tract mucosa •CLASSIC VENEREAL INFECTIONS: Neisseria gonorrhoeae (gonorrhoea), Treponema pallidum (syphilis), Haemophilus ducreyi (chancroid), Klebsiella granulomatis (granuloma inguinale), Chlamydia trachomatis serotypes L1-L3 (lymphogranuloma venereum) •OTHER SEXUALLY TRANSMITTED DISEASES (STD): Ch. trachomatis D-K, Mycoplasma hominis, Ureaplasma urealyticum; papillomaviruses, HBV, HCV, HSV-2, HIV-1; Candida albicans; Trichomonas vaginalis Conjunctiva and cornea •CONJUNCTIVA: Str. pneumoniae, S. aureus, H. influenzae, Moraxella lacunata; Chlam. trachomatis D-K, N. gonorrhoeae; adenoviruses (types 3, 8, 19), enteroviruses (type 70), HSV •CORNEA: S. aureus, Strept. pneumoniae, P. aeruginosa; Acanthamoeba castellanii; Bacillus cereus; oportunistically pathogenic moulds; HSV, VZV, adenoviruses (type 8) Skin and hypodermis – I •INTACT SKIN: leptospirae, larvae of hookworms (Ancylostoma duodenale, Necator americanus) and Strongyloides stercoralis, cercariae of schistosomes, bilharziellae and trichobilharziae (swimmers itch) •SMALL CRACKS IN SKIN: S. aureus, S. pyogenes, Bacillus anthracis, F. tularensis, Rickettsia prowazekii; wart viruses, milker´s nodes v., cowpox virus; dermatophytes •BITE OF ARTHROPODS: arboviruses; borreliae, ehrlichiae, rickettsiae, coxiellae, bartonellae, Yersinia pestis; malaric plasmodia, leishmaniae, trypanosomes & others) Skin and hypodermis – II •WOUNDS: S. aureus, S. pyogenes, Clostridium tetani, gas gangrene clostridia, coagulase negative staphylococci etc. •WOUNDS AND BITES BY ANIMALS: rabies v., Spirillum minus, Pasteurella multocida, Capnocytophaga canimorsus, S. aureus, Streptobacillus moniliformis; Erysipelothrix rhusiopathiae (erysipeloid), Burkholderia pseudomallei •BURNS: Pseudomonas aeruginosa, pyogenic cocci • • Skin and hypodermis – III •WOUNDS IN WATER: Pseudomonas aeruginosa, Aeromonas hydrophila; Vibrio vulnificus, V. parahaemolyticus, Mycobacterium marinum •WOUNDS IN THE TROPICS: Dermatophilus congolensis, Rhodococcus equi, Mycobacterium ulcerans, Mycob. marinum; Sporothrix schenckii and many other micromycetes Placenta •Congenital infections (= infections acquired during pregnancy) •VIRAL: rubella v. (Rubivirus), parvovirus B19 (Erythrovirus), cytomegalovirus (CMV), varicella-zoster v. (VZV), herpes simplex v. (HSV) •BACTERIAL: Treponema pallidum, Listeria monocytogenes •PARASITIC: Toxoplasma gondii •… Recommended reading material •Paul de Kruif: Microbe Hunters •Paul de Kruif: Men against Death •Axel Munthe: The Story of San Michele •Sinclair Lewis: Arrowsmith •André Maurois: La vie de Sir Alexander Fleming •Michael Crichton: Andromeda Strain •Albert Camus: Peste (The Plague) •Victor Heisser: An American Doctor Odyssey • • • •Please mail me other suggestions at: •mvotava@med.muni.cz •Thank you for your attention • • •