1. 口腔微生物免疫學 細菌感染 Bacterial infection 陳玉昆副教授: 高雄醫學大學 口腔病理科 07-3121101~2755 1

2. 學 習 目 標 Understand: Virulence factor of bacteria Koch postulates
Two main oral bacterial lesions
- Caries/periapical lesions
- Periodontitis
4. Tuberculosis
5. Syphilis

3. 參考書目
References
Siqueira JF. Endodontic infections: Concepts, paradigms, and perspectives. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2002;94:281-93
Hoang MD et al, Secondary syphilis: a histologic and immunohistochemical evaluation. J Cutan Pathol 2004: 31: 595-9
Zeltser R & Kurban AK. Syphilis. Clin Dermatology 2004;22:461-8
Yepes JF et al, Tuberculosis: Medical management update. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2004;98:267-73
結核病教學參考教材-衛生署疾病管制局
黃吉志 結核病的歷史回顧與展望 高醫醫訊 94年7月
張肇益 淺論牙周病病原菌、內毒素及宿主免疫反應 牙橋 2003;16:30-7
Slots J & Taubman MA. Contemporary oral microbiology & Immunology. First edition, 1992 Chapter 11, p
Kaohsiung Medical University, Oral Pathology Department
Ficarra G, Carlos R. Syphilis: The renaissance of an old disease with oral implications. Head and Neck Pathol DOI /s

4. Bacterial Infection Host Parasite Pathogen Virulence factors
Commensal
No damage
(latent/dormant)
Host
Bacterial Infection
Pathogen
Adherence, extracellular enzymes,
fibrinolysin, toxin
Virulence factors
Damage

5. Koch’s postulates The microorganism occurs in every case of the
disease can account for the pathologic changes
and clinical course of the disease
The microorganism occurs in no other disease
as a fortuitous and nonpathogenic parasite

6. Koch’s postulates
After it is isolated from the diseased host & grown in pure
culture, the microorganism can induce the disease anew
Organism isolated from lesions
Grown in pure culture in vitro
Pure culture
Animal
A similar disease
Organism reisolated
Help! I have been infected
哈 哈

7. Koch’s postulates Shortcomings Limitations
Isolated from patients both with and without cholera,
Vibrio cholerae failed to experimentally induce the
disease in animals
Limitations
Place considerable emphasis on pathogenicity, which
resides particularly in the microorganism
Dependence on host susceptibility is an unquestionable issue
Emphasize the ability to cultivate the causative micro-
organism in pure culture
Some diseases, such as syphilis and leprosy, for which
the causative bacterium has not yet been cultured

8. Koch’s postulates Limitations
Imply that all strains of a given microbial species are
equally virulent
It is known that different strains within a species vary
in virulence
Suggest that only a single species causes each disease
There are some diseases, such as periradicular diseases, that are induced by a mixture of different microbial species
Require that the suspected microorganism, after reino- culation into an animal, produce the S/S of the disease
Several human pathogens either do not cause the disease in animals or cause a disease with different characteristics from the human form of the disease

9. 牙 周 病 細 菌 口腔兩大疾病 齲 齒 病原菌: Two Main Bacterial Infections
Streptococus mutans
Gram (-)
> 200 different microbial species can be found in infected
root canals, usually in combinations of 4 to 7 species/canal
Theoretically, any one of these species would have the
potential to be an endodontic pathogen

10. Requirements for endodontic pathogen (1)
The microorganism must be present in sufficient number
to initiate and maintain the periradicular disease
The microorganism must possess an array of virulence
factors, which should be expressed during root canal
infection
The microorganism must be spatially located in the root canal system in such a way that it or its virulence factors can gain access to the periradicular tissues
The root canal environment must permit the survival and growth of the microorganism and provide signals or cues that stimulate the expression of virulence genes

11. Requirements for endodontic pathogen (2)
Inhibiting microorganisms must be absent or present in low numbers in the root canal environment
The host must mount a defense strategy at the periradicular tissues, inhibiting the spread of the infection. This process will result in tissue damage
Ref: 1

12. 牙 周 病 細 菌 牙科 兩大 疾病 齲 齒 Two Main Bacterial Infections Specific
牙科 兩大 疾病
牙 周 病
齲 齒
1930
1890
1970
1990
Specific
Non- specific
Spirochete
Amoeba
Bacteroides
A. Actinomycetemcomitans
P. gingivalis
P. Intermedia
C. Rectus
B. Forsythus
Gram (-)
病 原 菌

13. 牙 周 病 特 定 病 原 菌 的 條 件 該種細菌必須能夠大量於發病時存在， 而於健康時則僅有少數或甚至沒有
該種細菌所引發之抗體價在血清，唾液
或牙齦溝液中必須要高
清除或抑制該種細菌將迅速去除或舒緩病症
病巢部的組織，若使用該種細菌之抗體來操作
螢光抗體染色法，病巢部之組織能被染色標記
該種細菌必須能夠產生致病毒素或致病原因子
該種細菌之接種必須能夠讓實驗室的無菌動物
也引發相同的病程及症狀

14. Principal bacteria associated with periodontal diseases
Porphyromonas gingivalis,
Prevotella intermedia,
B. forsythus,
Campylobacter rectus
Adult periodontitis
Bacteroides forsythus,
P. gingivalis,
Campylobacter rectus,
P. intermedia
Refractory
periodontitis
Actinobacillus actinomycetemcomitans,
Capnocytophaga
Localized juvenile
periodontitis
Periodontitis in
juvenile diabetics
P. intermedia
Pregnancy
gingivitis
P. intermedia,
Intermediate-sized-
spirochetes
ANUG

15. 牙 周 病 病 原 菌 之 致 病 力 間 接 效 應 直 接 效 應 牙 周 組 織 牙 周 病 病 原 菌
Fimbria
牙 周 病 病 原 菌
牙 周 組 織
Inhibition of PMN
Leukotoxin, chemotaxis inhibitors,
phagocytosis & intracellular killing,
resistance to C-mediated killing
Lymphocyte alterations
Endotoxicity
IgA, IgG proteases
Fibrinolysin
Superoxide dismutase
Catalase
間 接 效 應
Enzymes
Collagense, hyaluronidase,
phospholipase, phosphatases
Exotoxin
Endotoxin
Cell inhibitors
Ammonia
直 接 效 應

16. Endotoxin - lipopolysaccharide (LPS)
Outer membrane
Inner membrane
Peptidoglycan
Lipoprotein
Phospholipid
Lipid A
Core Polysaccharide
O antigen
Side chain
O antigen
polysaccharide
Core polysaccharide
Lipid A
化學結構
Smooth O antigen
Semi-rough- 1-2 O antigen
Rough- no O antigen
Refs: 7,8

17. Endotoxin - lipopolysaccharide (LPS)
毒性強, 可直接對組織產生傷害,
亦會產生不良的免疫反應
可 :
造成 Leukopenia
活化XII blood clotting factor, 影響凝血機制
活化變異的補體反應
毒害fibroblast
引發骨吸收
活化巨噬細胞以製造IL-1,TNF-種種組織分解酶
亦產生過氧化物或離子基

18. Tuberulosis Mycobacterium tuberculosis Granulomatous inflammation &
Aerosols
Lung
Granulomatous inflammation &
tubercle
Caseation necrosis
(liquefy, cavitation,
fibrosis & calcification)
Ghon complexe
(radiodensities)
Hematogenate route
Mycobacterium tuberculosis
Miliary tuberculosis
Difficult to destain with acid once stained
(acid-fast stain)
High lipid content
Virulence factor: Cord factor ( a glycolipid of trehalose & mycolic acid)
inhibition of PMN, attack mitochondrial memb causing
damage to respiratory &/or oxidative system, elicit
granulomatous formation
: PPD (purified protein derivative)
(no toxin)
Koch phenomenon (partial immunity to reinfection)
Ref: 9

19. Ref: 5

20. 結核桿菌 Mycobacterium tuberculosis
Ref: 5

21. M tuberculosis Aerobic Non-motile Non-spore forming Slow growing
Bacilli
M tuberculosis
Cell wall
CD 14
Fc receptors
Surfactant protein
receptor
Complement
receptors
High molecular
weight lipids
Glycolipids
Mycolic acids
Aerobic
Non-motile
Non-spore forming
Slow growing
Refs: 4, 9

22. Primary Infection Pulmonary manifestation 80-84% Latent Active
Coughing
Bacilli
Pulmonary
manifestation
80-84%
Latent
Active
Extrapulmonary
manifestation
16-20%
Immunosuppression
Malnutrition
Vitamin D deficiency
Refs: 4, 9

23. 結 核 病 的 傳 染 途 徑
Ref: 5

24. Ref: 5

25. 只要number of cells = 10 可被感染
Ref: 5

26. Ref: 5

27. Ref: 5

28. Ref: 5

29. Ref: 5

30. 2002年 各國結核病發生率比較
台灣肺結核
Ref: 6

31. New cases – 14,486 (2001)
Bacilli
Ref: 5

32. Ref: 5

33. Risk Group
(RG) = 3
Ref: 5

34. Syphilis Primary Tertiary Treponema pallidum Secondary
(10 days to 10 wks, average 3 wks after contact)
Chancre (genitalis,
oral, perineal)
Lymphadenopathy
(lymph node)
Tertiary
(months or years
after 2nd stage)
Skin (gumma),
CNS (tabes
dorsalis),
Circulatory
system (aortic
aneurysm)
Treponema pallidum
Secondary
(2 to 12 wks, after chancre)
Generalized rash,
Flu symptoms,
Bone lesions
(anywhere or
everywhere)
Congenital
Hutchinson triad
Placenta
Wassermann Ab
Non-specificity
IgM
Index of severity
Treponemal Ab
Specificity
IgG
Index of severity
3 wks

35. Natural history of untreated syphilis
Primary incubation
Primary syphilis
Secondary incubation
Late latent syphilis (asymptomatic)
Tertiary syphilis: cardiovascular syphilis
Tertiary syphilis: gummatous disease
Tertiary syphilis
late neurosyphilis
Secondary syphilis
Transmittable
sexually
or mother to
child
mother to
Non-
Central nervous
system invasion
Recurrence
10-90 days from exposure
Chancre formation
4-10 weeks after chancre formation
1 year or less postinfection
10% (20-30 years postinfection)
25-60%
Tabes dorsalis (2-9%)
(Onset 3-50 years postinfection)
General paresis (2-9%)
(Onset 2-30 years postinfection)
15% (1-46 years postinfection)
More than 1 year postinfection
Early latent syphilis (asymptomatic)
Exposure
Early
neurosyphilis
Symptomatic in
only 5%
Meningitis
Cranial neuritis
Ocular involvement
Meningiovascular disease
Ref: 3

36. Natural history of untreated syphilis
Ref: 10
TERTIARY SYPHILIS

37. Constitutional and mucocutaneous manifestations of secondary syphilis
Symptoms: fever, malaise, weight loss
Skin rash (symmetrical and generalized), alopecia
Condyloma latum in intertriginous areas
Lymphadenopathy
Oral involvement: multiple mucous patches covered by grayish,
white pseudomembranes and surrounded by erythema
Ocular involvement: uveitis, iritis, optic neuritis
Arthritis, periostitis
Hepatitis
Glomerulonephritis
Neurologic involvement: headache, meningitis, cranial nerve
paralysis, cerebrovascular accident
Ref: 10

38. Syphilis: The Renaissance of an Old Disease with Oral Implications
Painless oral ulcer
Oral chancer
An important diagnostic criteria
Ref: 3

39. Manifestations of untreated syphilis
Chancer
Secondary syphilis: truncal macular- papular eruption
(頂端切平)
Ref: 3

40. Manifestations of untreated syphilis
Secondary syphilis: oral mucous patch
Secondary syphilis: papular syphilis of the palms
Ref: 3

41. Manifestations of untreated syphilis
Secondary syphilis: moth-
eaten alopecia of the scalp
Congenital syphilis: mulberry molar
Secondary syphilis:
loss of lateral eyebrow
Tertiary syphilis: ulcerated gumma of the leg
Ref: 3

42. Manifestations of untreated syphilis
Secondary syphilis: maculopapular skin lesions of the neck
Secondary syphilis: maculopapular and scaly lesions of the plantar area
Secondary syphilis:
moth-eaten alopecia
(浸軟)
Macerated plaques (condylomata lata) of the toe webs
Ref: 10

43. Manifestations of untreated syphilis
Ulceronodular skin lesion of lue (梅毒) maligna (致命)
Secondary oral syphilis: mucous patches covered by grayish, white pseudo-membranes of the lower vestibular mucosa
Ref: 10
Secondary oral syphilis:
with lesions on the soft palate
Oral chancre in a promiscuous woman who had unprotected oral sex

44. Detection of spirochytes
Silver stain
Immunocyochemical stain
Immunocyochemical stain
Immunocyochemical stain
Ref: 2

45. Summaries Knowing: Virulence factor of bacteria Koch postulates
Two main oral bacterial lesions
- Caries/periapical lesions
- Periodontitis
4. Tuberculosis
5. Syphilis