口腔微生物免疫學

Bacterial infection
細菌感染

陳玉昆教授: 高雄醫學大學 口腔病理科

07-3121101~2755
yukkwa@kmu.edu.tw
 學習目標
Understand:
1. Virulence factor of bacteria
2. Koch postulates
3. Two main oral bacterial lesions
- Caries/periapical lesions
- Periodontitis
4. Tuberculosis
5. Syphilis
 參考書目
References
1. Siqueira JF. Endodontic infections: Concepts, paradigms, and perspectives. Oral Surg
Oral Med Oral Pathol Oral Radiol Endod 2002;94:281-93
2. Hoang MD et al, Secondary syphilis: a histologic and immunohistochemical evaluation.
J Cutan Pathol 2004: 31: 595-9
3. Zeltser R & Kurban AK. Syphilis. Clin Dermatology 2004;22:461-8
4. Yepes JF et al, Tuberculosis: Medical management update. Oral Surg Oral Med Oral
Pathol Oral Radiol Endod 2004;98:267-73
5. 結核病教學參考教材-衛生署疾病管制局
6. 黃吉志 結核病的歷史回顧與展望 高醫醫訊 94年7月
7. 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
8. Slots J & Taubman MA. Contemporary oral microbiology & Immunology. First
edition, 1992 Chapter 11, p. 165-190
9. Kaohsiung Medical University, Oral Pathology Department
10. Ficarra G, Carlos R. Syphilis: The renaissance of an old disease with oral
implications. Head and Neck Pathol DOI 10.1007/s12105-009-0127-0
 Bacterial Infection
(latent/dormant) No damage
Commensal(共生)
Parasite Host
(寄生體)

Pathogen(病原體) Damage

Virulence factors

Adherence, extracellular enzymes,

fibrinolysin, toxin
 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(偶然) and nonpathogenic parasite
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

Help! I have been infected

Pure culture Animal A similar disease

Organism reisolated 哈哈
Koch’s postulates Shortcomings
Isolated from patients both with and without cholera(霍亂),
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(感受性) is an
unquestionable issue
Emphasize the ability to cultivate the causative micro-
organism in pure culture
 Some diseases, such as syphilis & leprosy(麻瘋), for
which the causative bacterium has not yet been cultured
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
 Two Main Bacterial Infections

牙周病
口腔兩大疾病 細菌

齲齒
病原菌:
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
 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
 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
 Two Main Bacterial Infections

牙周病
牙科 兩大 疾病 細菌
齲齒
病原菌
Specific Non- specific Specific Gram (-)
A. Actinomycetemcomitans
Spirochete Bacteroides P. gingivalis
Amoeba Spirochete P. Intermedia
C. Rectus
B. Forsythus
1890 1930 1970 1990
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
Principal bacteria associated with
periodontal diseases
Adult periodontitis Porphyromonas gingivalis,
Prevotella intermedia,
B. forsythus,
Campylobacter rectus
Refractory Bacteroides forsythus,
P. gingivalis,
periodontitis Campylobacter rectus,
P. intermedia

Localized juvenile Actinobacillus actinomycetemcomitans,

Capnocytophaga
periodontitis
Periodontitis in Capnocytophaga
Actinobacillus actinomycetemcomitans,
juvenile diabetics
Pregnancy P. intermedia
gingivitis
ANUG P. intermedia,
Intermediate-sized-
spirochetes
 牙周病病原菌之致病力

Fimbria
牙周組織
牙周病病原菌

直接效應 間接效應
Enzymes Inhibition of PMN
Collagense, hyaluronidase, Leukotoxin, chemotaxis inhibitors,
phagocytosis & intracellular killing,
phospholipase, phosphatases
resistance to C-mediated killing
Exotoxin Lymphocyte alterations
Endotoxin Endotoxicity
Cell inhibitors IgA, IgG proteases
Ammonia Fibrinolysin
Superoxide dismutase
Catalase
 Endotoxin - lipopolysaccharide (LPS)

化學結構
O antigen
Side chain
Core Polysaccharide

Lipid A
Core polysaccharide O antigen
polysaccharide
Lipid A
Outer membrane

Smooth- 8-10 O antigen

Phospholipid

Lipoprotein
Semi-rough- 1-2 O antigen

Peptidoglycan

Inner membrane Rough- no O antigen

Refs: 7,8
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 (白細胞減少症)
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
 Tuberulosis

Aerosols Lung Granulomatous inflammation &

tubercle

Ghon complexe Caseation necrosis

(radiodensities) (liquefy, cavitation,
fibrosis & calcification)
Hematogenate route
Mycobacterium tuberculosis Miliary tuberculosis

Koch phenomenon (partial immunity to reinfection)

High lipid content Difficult to destain(退色) with acid once
stained (acid-fast stain抗酸性染色)
Virulence factor: Cord factor ( a glycolipid of trehalose & mycolic acid)
(no toxin) inhibition of PMN, attack mitochondrial memb causing
damage to respiratory &/or oxidative system, elicit
granulomatous formation
: PPD (purified protein derivative)
Ref: 9
Caseation necrosis

Ref: 5
結核桿菌(Mycobacterium tuberculosis)染色

螢光染色

抗酸性染色

Ref: 5
 結核桿菌(Mycobacterium
M tuberculosis tuberculosis)結構
Fc receptors Bacilli
High molecular Glycolipids
Surfactant protein weight lipids Mycolic acids
receptor

Complement
receptors

CD 14

螢光染色

Cell
Cellwall
wall
Aerobic
Non-motile
Non-spore forming 抗酸性染色
Slow growing Refs: 4, 9
結核病的病源

Ref: 4, 9
 結核病的傳染途徑
Primary Infection Coughing
Bacilli

Pulmonary
manifestation
80-84%
Latent Active

Extrapulmonary
manifestation
 Immunosuppression 16-20%
 Malnutrition
 Vitamin D deficiency
Refs: 4, 9
結核病的傳染途徑

Ref: 5
結核病的傳染途徑

只要number of cells = 10
可被感染

Ref: 5
結核病再活動的原因

Ref: 5
結 核 病 的 治 療(1)

Ref: 5
結 核 病 的 治 療(2)

Ref: 5
結核病 ~ 三千年歷史的古老疾病
埃及時代 西元前 3700-1000年

土偶 木乃伊(Nesperhan, priest of Amun)

Ref: 5
目前全球結核病狀況

Ref: 5
 2002年 各國結核病發生率比較
史瓦濟蘭 631
南非 481
菲律賓 151
越南 119
泰國
80
台灣 74.8
新加坡 36
日本 26 台灣肺結核
英國 12
瑞士
8
美國 5
冰島 3

0 10 100 1000人口
1/100,000
 Bacilli

Changing registration criteria

New cases – 14,486 (2001)

Ref: 5
臺灣結核病本國籍趨勢圖(2007-2014)
20000

15000
病例數(人)

10000

5000

2007 2008 2009 2010 2011 2012 2013 2014

建檔年

Ref: 5
結 核 病 防 治 原 則(1)

Ref: 5
結 核 病 防 治 原 則(2)

Risk Group
(RG) = 3

Ref: 5
 Syphilis
Primary Treponema pallidum Tertiary
(10 days to 10 wks, (months or years
average 3 wks after Secondary after 2nd stage)
contact) (2 to 12 wks, after Skin (gumma),
Chancre (genitalis, chancre) CNS (tabes
oral, perineal) Generalized rash, dorsalis),
Lymphadenopathy Flu symptoms, Circulatory
(lymph node) Bone lesions system (aortic
(anywhere or aneurysm)
Placenta
Congenital everywhere)
Hutchinson triad

Wassermann Ab Treponemal Ab
Non-specificity Specificity
IgM IgG
Index of severity Index of severity
 Natural history of untreated syphilis
Exposure

Primary incubation
Central nervous
10-90 days from exposure system invasion
Primary syphilis
25-60%
Chancre formation
Secondary incubation
4-10 weeks after chancre formation
Early
Secondary syphilis neurosyphilis
Transmittable

Recurrence
sexually Symptomatic in
Early latent syphilis (asymptomatic) only 5%
or mother to
child 1 year or less postinfection Meningitis
Cranial neuritis
Ocular involvement
Transmittable Meningiovascular disease
Late latent syphilis (asymptomatic)
mother to
child More than 1 year postinfection

Non- Tertiary syphilis

Tertiary syphilis: cardiovascular syphilis late neurosyphilis
Transmittable
10% (20-30 years postinfection)
Tabes dorsalis (2-9%)
(Onset 3-50 years postinfection)
Tertiary syphilis: gummatous disease
General paresis (2-9%)
15% (1-46 years postinfection) (Onset 2-30 years postinfection)

Ref: 3
Natural history of untreated syphilis

TERTIARY SYPHILIS

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

Ref: 10
Oral syphilis – re-emergence of
an old disease with oral
manifestations
Syphilis: The Renaissance(文藝復興) of
an Old Disease with Oral Implications

Painless oral ulcer Oral chancer

An important diagnostic criteria

Ref: 3
 Manifestations of untreated syphilis

Chancer

(頂端切平)
Secondary syphilis: truncal
macular- papular eruption

Ref: 3
 Manifestations of untreated syphilis

Secondary syphilis:
oral mucous patch
Secondary syphilis: papular syphilis
of the palms

Ref: 3
 Manifestations of untreated syphilis

Secondary syphilis: moth-eaten

Congenital syphilis: mulberry molar
alopecia(脫髮) of the scalp(頭皮)

Secondary syphilis: Tertiary syphilis: ulcerated gumma

loss of lateral eyebrow of the leg
Ref: 3
 Manifestations of untreated syphilis

Secondary syphilis:
maculopapular skin lesions Secondary syphilis: maculopapular
of the neck and scaly lesions of the plantar area

Secondary syphilis: (浸軟) Macerated plaques (condylomata

moth-eaten alopecia lata) of the toe webs Ref: 10
 Manifestations of untreated syphilis

Ulceronodular skin lesion Secondary oral syphilis: mucous patches

of lue (梅毒) maligna (致命) covered by grayish, white pseudo-
membranes of the lower vestibular mucosa

Secondary oral syphilis: Oral chancre in a promiscuous(淫亂) Ref: 10

with lesions on the soft palate woman who had unprotected oral sex
 Detection of spirochytes

Silver stain Immunocyochemical stain

Immunocyochemical stain Immunocyochemical stain

Ref: 2
 Summaries
Knowing:
1. Virulence factor of bacteria
2. Koch postulates
3. Two main oral bacterial lesions
- Caries/periapical lesions
- Periodontitis
4. Tuberculosis
5. Syphilis