Transcript DownLoad - 口腔病理科教學網

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
[email protected]
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
(latent/dormant)
Bacterial Infection
Commensal(共生)
Parasite
(寄生體)
Pathogen(病原體)
No damage
Host
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 microorganism 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 reinoculation 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
細菌
口腔兩大疾病
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
細菌
牙科 兩大 疾病
齲齒
病原菌
Specific Non- specific Specific
Spirochete
Amoeba
1890
1930
Bacteroides
Spirochete
Gram (-)
A. Actinomycetemcomitans
P. gingivalis
P. Intermedia
C. Rectus
B. Forsythus
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
Refractory
periodontitis
Porphyromonas gingivalis,
Prevotella intermedia,
B. forsythus,
Campylobacter rectus
Bacteroides forsythus,
P. gingivalis,
Campylobacter rectus,
P. intermedia
Localized juvenile
periodontitis
Periodontitis in
juvenile diabetics
Actinobacillus actinomycetemcomitans,
Capnocytophaga
Pregnancy
gingivitis
P. intermedia
ANUG
P. intermedia,
Intermediate-sizedspirochetes
Capnocytophaga
Actinobacillus actinomycetemcomitans,
牙周病病原菌之致病力
Fimbria
牙周病病原菌
牙周組織
直接效應
Enzymes
Collagense, hyaluronidase,
phospholipase, phosphatases
Exotoxin
Endotoxin
Cell inhibitors
Ammonia
間接效應
Inhibition of PMN
Leukotoxin, chemotaxis inhibitors,
phagocytosis & intracellular killing,
resistance to C-mediated killing
Lymphocyte alterations
Endotoxicity
IgA, IgG proteases
Fibrinolysin
Superoxide dismutase
Catalase
Endotoxin - lipopolysaccharide (LPS)
化學結構
O antigen
Side chain
Core Polysaccharide
Lipid A
Core polysaccharide O antigen
Lipid A
polysaccharide
Outer membrane
Phospholipid
Lipoprotein
Smooth- 8-10 O antigen
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)
inhibition of PMN, attack mitochondrial memb causing
(no toxin)
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
M
tuberculosis
結核桿菌(Mycobacterium
tuberculosis)結構
Bacilli
Fc receptors
Surfactant protein
receptor
High molecular Glycolipids
weight lipids
Mycolic acids
Complement
receptors
CD 14
螢光染色
Aerobic
Non-motile
Non-spore forming
Slow growing
Cell
Cellwall
wall
抗酸性染色
Refs: 4, 9
結核病的病源
Ref: 4, 9
結核病的傳染途徑
Coughing
Primary Infection
Bacilli
Pulmonary
manifestation
80-84%
Latent
Active
 Immunosuppression
 Malnutrition
 Vitamin D deficiency
Extrapulmonary
manifestation
16-20%
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
台灣肺結核
26
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
病例數(人)
15000
10000
5000
0
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
(10 days to 10 wks,
average 3 wks after
contact)
Chancre (genitalis,
oral, perineal)
Lymphadenopathy
(lymph node)
Treponema pallidum
Placenta
Congenital
Hutchinson triad
Wassermann Ab
Non-specificity
IgM
Index of severity
Secondary
(2 to 12 wks, after
chancre)
Generalized rash,
Flu symptoms,
Bone lesions
(anywhere or
everywhere)
Tertiary
(months or years
after 2nd stage)
Skin (gumma),
CNS (tabes
dorsalis),
Circulatory
system (aortic
aneurysm)
Treponemal Ab
Specificity
IgG
Index of severity
Natural history of untreated syphilis
Exposure
Primary incubation
10-90 days from exposure
Primary syphilis
Central nervous
system invasion
25-60%
Chancre formation
Secondary incubation
4-10 weeks after chancre formation
Early
neurosyphilis
Secondary syphilis
Transmittable
mother to
child
NonTransmittable
Late latent syphilis (asymptomatic)
Recurrence
Transmittable
sexually
Early latent syphilis (asymptomatic)
or mother to
1 year or less postinfection
child
Symptomatic in
only 5%
Meningitis
Cranial neuritis
Ocular involvement
Meningiovascular disease
More than 1 year postinfection
Tertiary syphilis: cardiovascular syphilis
Tertiary syphilis
late neurosyphilis
10% (20-30 years postinfection)
Tertiary syphilis: gummatous disease
15% (1-46 years postinfection)
Tabes dorsalis (2-9%)
(Onset 3-50 years postinfection)
General paresis (2-9%)
(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 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
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
alopecia(脫髮) of the scalp(頭皮)
Secondary syphilis:
loss of lateral eyebrow
Congenital syphilis: mulberry molar
Tertiary syphilis: ulcerated gumma
of the leg
Ref: 3
Manifestations of untreated syphilis
Secondary syphilis:
maculopapular skin lesions
of the neck
Secondary syphilis:
moth-eaten alopecia
Secondary syphilis: maculopapular
and scaly lesions of the plantar area
(浸軟) Macerated plaques (condylomata
lata) of the toe webs
Ref: 10
Manifestations of untreated syphilis
Ulceronodular skin lesion
of lue (梅毒) maligna (致命)
Secondary oral syphilis:
with lesions on the soft palate
Secondary oral syphilis: mucous patches
covered by grayish, white pseudomembranes of the lower vestibular mucosa
Oral chancre in a promiscuous(淫亂) Ref: 10
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