口腔微生物免疫學 bacterial infection 細菌感染 陳玉昆副教授 : 高雄醫學大學...
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學 習 目 標
Understand:1. Virulence factor of bacteria2. Koch postulates3. Two main oral bacterial lesions - Caries/periapical lesions - Periodontitis4. Tuberculosis5. Syphilis
Understand:1. Virulence factor of bacteria2. Koch postulates3. Two main oral bacterial lesions - Caries/periapical lesions - Periodontitis4. Tuberculosis5. Syphilis
參考書目
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;22:461-84. Yepes JF et al, Tuberculosis: Medical management update. Oral Surg Oral Med Oral
Pathol Oral Radiol Endod 2004;98:267-735. 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;16:30-78. Slots J & Taubman MA. Contemporary oral microbiology & Immunology. First
edition, 1992 Chapter 11, p. 165-1909. Kaohsiung Medical University, Oral Pathology Department10.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
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;22:461-84. Yepes JF et al, Tuberculosis: Medical management update. Oral Surg Oral Med Oral
Pathol Oral Radiol Endod 2004;98:267-735. 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;16:30-78. Slots J & Taubman MA. Contemporary oral microbiology & Immunology. First
edition, 1992 Chapter 11, p. 165-1909. Kaohsiung Medical University, Oral Pathology Department10.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
References
Pathogen
Adherence, extracellular enzymes,fibrinolysin, toxin
Virulence factors
Damage
Parasite Commensal
No damage(latent/dormant)
Host
Bacterial Infection
Koch’s postulates
The microorganism occurs in every case of thedisease can account for the pathologic changesand clinical course of the disease
The microorganism occurs in no other diseaseas a fortuitous and nonpathogenic parasite
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
After it is isolated from the diseased host & grown in pure
culture, the microorganism can induce the disease anew
Koch’s postulates
Koch’s postulates ShortcomingsIsolated from patients both with and without cholera,Vibrio cholerae failed to experimentally induce thedisease in animals
Place considerable emphasis on pathogenicity, whichresides particularly in the microorganism Dependence on host susceptibility is an unquestionable issue
Limitations
Emphasize the ability to cultivate the causative micro-organism in pure culture Some diseases, such as syphilis and leprosy, for whichthe causative bacterium has not yet been cultured
Koch’s postulatesLimitations
Imply that all strains of a given microbial species are equally virulentIt is known that different strains within a species varyin 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
病原菌 : Streptococus mutansGram (-)
齲 齒
細 菌口腔兩大疾病牙 周 病
> 200 different microbial species can be found in infectedroot canals, usually in combinations of 4 to 7 species/canalTheoretically, any one of these species would have the potential to be an endodontic pathogen
Two Main Bacterial Infections
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 (1)
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
19301890 1970 1990
Specific Non- specific Specific
SpirocheteAmoeba
BacteroidesSpirochete
A. ActinomycetemcomitansP. gingivalisP. IntermediaC. RectusB. Forsythus
Gram (-)
病 原 菌
細 菌牙科 兩大 疾病牙 周 病
齲 齒
Two Main Bacterial Infections
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 withperiodontal diseases
Porphyromonas gingivalis, Prevotella intermedia,B. forsythus,Campylobacter rectus
Adult periodontitis
Bacteroides forsythus, P. gingivalis,Campylobacter rectus,P. intermedia
Refractoryperiodontitis
Actinobacillus actinomycetemcomitans, Capnocytophaga
Localized juvenileperiodontitis
Capnocytophaga Actinobacillus actinomycetemcomitans,
Periodontitis in juvenile diabetics
P. intermediaPregnancygingivitis
P. intermedia,Intermediate-sized-spirochetes
ANUG
牙 周 病 病 原 菌牙 周 組 織
Enzymes Collagense, hyaluronidase, phospholipase, phosphatasesExotoxinEndotoxinCell inhibitorsAmmonia
直 接 效 應Inhibition of PMN Leukotoxin, chemotaxis inhibitors, phagocytosis & intracellular killing, resistance to C-mediated killing
Lymphocyte alterationsEndotoxicityIgA, IgG proteasesFibrinolysinSuperoxide dismutaseCatalase
間 接 效 應
Fimbria
牙 周 病 病 原 菌 之 致 病 力牙 周 病 病 原 菌 之 致 病 力
Endotoxin - lipopolysaccharide (LPS)
O antigenpolysaccharide
Core polysaccharide Lipid A
化學結構
Smooth- 8-10 O antigen
Semi-rough- 1-2 O antigen
Rough- no O antigen
Outer membrane
Inner membrane
Peptidoglycan
Lipoprotein
Phospholipid
Lipid A
Core Polysaccharide
O antigenSide chain
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 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
Aerosols
Caseation necrosis(liquefy, cavitation,fibrosis & calcification)
Ghon complexe (radiodensities)
Hematogenate route
Mycobacterium tuberculosis Miliary tuberculosis
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)
Tuberulosis
Difficult to destain with acid once stained(acid-fast stain)
High lipid content
Granulomatous inflammation &tubercle
Lung
Ref: 9
Ref: 5
結核桿菌 Mycobacterium tuberculosis
Ref: 5
Bacilli
M tuberculosis
Cell wallCell wall
CD 14
Fc receptors
Surfactant proteinreceptor
Complementreceptors
High molecularweight lipids
GlycolipidsMycolic acids
AerobicNon-motileNon-spore formingSlow growing
Refs: 4, 9
BacilliPrimary Infection
Pulmonary manifestation80-84%
Extrapulmonary manifestation16-20%
ActiveLatent
Immunosuppression Malnutrition Vitamin D deficiency
Coughing
Refs: 4, 9
結 核 病 的 傳 染 途 徑
Ref: 5
Ref: 5
Ref: 5
只要 number of cells = 10 可被感染
只要 number of cells = 10 可被感染
Ref: 5
Ref: 5
Ref: 5
Ref: 5
2002 年 各國結核病發生率比較
台灣肺結核
Ref: 6
New cases – 14,486 (2001)
Bacilli
Ref: 5
Ref: 5
Ref: 5
Risk Group(RG) = 3
Risk Group(RG) = 3
Syphilis
Primary(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)
Secondary(2 to 12 wks, after chancre) Generalized rash, Flu symptoms, Bone lesions (anywhere or everywhere)
Treponema pallidum
Wassermann Ab Non-specificity IgM Index of severity
Treponemal Ab Specificity IgG Index of
severity
3 w
ksCongenital Hutchinson triad
Placenta
Primary incubation
Primary syphilis
Secondary incubation
Late latent syphilis (asymptomatic)
Tertiary syphilis: cardiovascular syphilis
Tertiary syphilis: gummatous disease
Tertiary syphilislate neurosyphilis
Secondary syphilis
Transmittablesexually
or mother tochild
Transmittablemother to
child
Non-Transmittable
Central nervoussystem invasion
Recu
rrence
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
Earlyneurosyphilis
Symptomatic in only 5%Meningitis
Cranial neuritisOcular involvement
Meningiovascular disease
Natural history of untreated syphilis
Ref: 3
Natural history of untreated syphilis
Ref: 10
TERTIARY SYPHILISTERTIARY SYPHILIS
Constitutional and mucocutaneous manifestations of secondary syphilis
Ref: 10
Symptoms: fever, malaise, weight lossSkin rash (symmetrical and generalized), alopeciaCondyloma latum in intertriginous areasLymphadenopathyOral involvement: multiple mucous patches covered by grayish, white pseudomembranes and surrounded by erythemaOcular involvement: uveitis, iritis, optic neuritisArthritis, periostitisHepatitisGlomerulonephritisNeurologic involvement: headache, meningitis, cranial nerve paralysis, cerebrovascular accident
Painless oral ulcer Oral chancer
An important diagnostic criteria
Ref: 3
Syphilis: The Renaissance of an Old Disease with Oral Implications
Manifestations of untreated syphilis
Chancer
Ref: 3
Secondary syphilis: truncal macular- papular eruption
( 頂端切平 )( 頂端切平 )
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 of the scalp
Secondary syphilis: loss of lateral eyebrow
Tertiary syphilis: ulcerated gumma of the leg
Congenital syphilis: mulberry molar
Ref: 3
Manifestations of untreated syphilis
Secondary syphilis: maculopapular skin lesions of the neck
Secondary syphilis: moth-eaten alopecia
Macerated plaques (condylomata lata) of the toe webs
Secondary syphilis: maculopapular and scaly lesions of the plantar area
Ref: 10( 浸軟 )( 浸軟 )
Manifestations of untreated syphilis
Ulceronodular skin lesion of lue ( 梅毒 ) maligna ( 致命 )
Secondary oral syphilis: with lesions on the soft palate
Oral chancre in a promiscuous woman who had unprotected oral sex
Secondary oral syphilis: mucous patches covered by grayish, white pseudo-membranes of the lower vestibular mucosa
Ref: 10
Detection of spirochytes
Silver stain
Immunocyochemical stain
Immunocyochemical stain
Immunocyochemical stainRef: 2
Summaries
Knowing:1. Virulence factor of bacteria2. Koch postulates3. Two main oral bacterial lesions - Caries/periapical lesions - Periodontitis4. Tuberculosis5. Syphilis
Knowing:1. Virulence factor of bacteria2. Koch postulates3. Two main oral bacterial lesions - Caries/periapical lesions - Periodontitis4. Tuberculosis5. Syphilis