1. The 10th lecture for 2nd-year students of Dentistry
Institute for Microbiology, Medical Faculty of Masaryk University and St. Anna Faculty Hospital in Brno
Miroslav Votava
PATHOGENESIS
OF INFECTION
The 10th lecture for 2nd-year students of Dentistry
April 23rd , 2014

2. 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

3. 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

4. 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

5. Damage by direct effect of infectious agent
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

6. Damage as a result of defence reactions – a)
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

7. Damage as a result of defence reactions – b)
Toxicity – III
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 …

8. What is the pathogenesis?
Pathogenesis explains the origin and development of pathological symptoms
What does the pathogenesis of infection include?
The way the agent spreads through the macroorganism
Mechanisms of defence against it
Actual causes of symptoms:
a) either the infectious agent itself,
b) or the reaction of macroorganism to it

9. 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

10. PORTALS OF the infectious agent’s ENTRY
Mucosae
respiratory ways and lungs
alimentary tract
urogenital tract
conjunctiva and cornea
Skin and hypodermis
Placenta

11. 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

12. 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

13. 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

14. 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

15. 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)

16. 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

17. 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)

18. 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)

19. 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

20. 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

21. Congenital infections (= infections acquired during pregnancy)
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

22. SPREAD OF INFECTION (dissemination of the agent)
By means of
a) lymph
b) blood
c) per continuitatem
d) along nerves

23. a) Spreading by means of lymph
skin → regional lymphatic nodes: pyogenic cocci, F. tularensis, Y. pestis; arboviruses
oropharynx, tonsils → cervical nodes: S. pyogenes, C. diphtheriae, M. tuberculosis, anaerobes (Actinomyces israeli, Prevotella), T. gondii
lungs → hilar nodes: M. tbc, B. anthracis, other respiratory pathogens
genital mucosa → inguinal nodes: Treponema pallidum, Ch. trachomatis L1-L3, H. ducreyi
Peyer plaques → mesenteric nodes: Yersinia enterocolitica, enteric adenoviruses, enteroviruses

24. b) Spreading by means of blood
Agents of all generalized infections: exanthematic viruses, enteroviruses, arboviruses, Treponema pallidum, Salmonella Typhi and many others
Agents of pneumonia commonly appear in blood: especially Strept. pneumoniae
As complications agents of other systemic and local infections: during meningitis, pyelonephritis (urosepsis), suppurating wounds and suchlike

25. c) Spreading per continuitatem
From cell to cell: HSV, RSV, listeriae, yersiniae
By means of secretion down the mucosa: agents of respiratory, enteric and urogenital infections
From the site of arthropod biting to its vicinity: arboviruses, Borrelia burgdorferi
From the wound to adjacent tissue: Streptococcus pyogenes, Clostridium perfringens
From the middle ear to meninges: S. pneumoniae, Haemophilus influenzae type b
From lungs to pleura: agents of pneumonia

26. d) Spreading along nerves
Either axonally (within nerve fibres)
or by progressive infection of Schwann sheath
Herpes simplex v., varicella-zoster v., B-virus, rabies virus
Mycobacterium leprae
Naegleria fowleri
tetanic toxin

27. ELIMINATION OF AGENTS FROM THE BODY
From the mucosa of respiratory tract and oral cavity, intestine, urogenital tract,
eye
From skin lesions
By means of urine
From blood

28. Elimination from respiratory tract
Sneezing:
in particular agents of common cold (rhinoviruses, coronaviruses),
from bacteria e.g. Neisseria meningitidis
Coughing:
other respiratory viruses (primarily influenza virus),
exanthematic viruses (VZV, morbilli virus, rubella virus),
Neiss. meningitidis, Bordetella pertussis, Mycob. tuberculosis, Yersinia pestis

29. Elimination from alimentary tract
Saliva:
HSV, EBV, mumps virus, Str. pyogenes
Stool:
enteroviruses (incl. poliovirus), HAV, HEV
salmonellae incl. Salm. Typhi, shigellae, EPEC, ETEC etc., V. cholerae, C. difficile
Entamoeba histolytica, Giardia lamblia
Ascaris lumbricoides, Taenia saginata

30. Elimination from urogenital tract
From diseased mucosae:
Agents of classic venereal infections: in Europe Neiss. gonorrhoeae, Treponema pallidum
Agents of other sexually transmitted diseases (STD): Chlamydia trachomatis serotypes D-K, papillomaviruses, HSV-2
By means of urine:
Salmonella Typhi
Agents of congenital infections (rubella virus, CMV)
Exotic viruses of hemorrhagic fevers (Ebola)

31. Elimination from skin lesions
Staphylococcus aureus
Streptococcus pyogenes
Varicella-zoster virus (agent of chickenpox and shingles)
Papillomaviruses (agents of warts)
Dermatophytes (e.g. Trichophyton rubrum, Microsporum canis, Epidermophyton floccosum)
Sarcoptes scabiei (itch-mite)

32. Elimination from blood
By means of vectors:
tick-borne encephalitis virus – ticks, yellow fever virus – mosquitoes
Rickettsia prowazekii – lice, Yersinia pestis – fleas, Borrelia recurrentis – lice
Malaric plasmodia – mosquitoes
By means of small cracks in mucosa: HBV, HIV …

33. 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 Hans Zinsser: Rats, Lice, and History Michael Crichton: Andromeda Strain Albert Camus: Peste Victor Heisser: An American Doctor Odyssey Richard Preston: The Hot Zone Please mail me other suggestions at: Thank you for your attention