大二下学习-微生物课件12级tbdiph生长慢,人型、牛型

Mycobacteriap.153Rod-shaped,

aerobic

bacteria,Acid-fastbacilli.No

capsule,

no

flagellum,

no

exotoxinand

no

endotoxin.>100

speciesMainly

pathogen

of

human:M.

tuberclosis,

and

M.

bovis

---

tuberclosisM.

leprae---leprosyM.

aviumintracellulare

---opportunistic

infectionof

AIDS结核分枝杆菌生长慢,人型、牛型非结核分枝杆菌I组生长慢,堪萨斯非结核分枝杆菌II组生长慢，癗疠非结核分枝杆菌III组生长慢,鸟胞内分枝杆菌非结核分枝杆菌IV组生长快速，龟分枝麻风分枝杆菌不生长tones

of

the

historyKoch

found

M.

tuberculosis

in

1882

(Germany)Koch

discovered

tuberculin

in

1890

(Germany)Calmettle

&

Guerin

made

BCG

in

1921

(France)chemo-therapy

began

in

1940Re-emerging

after

80’s

of

20

centurydrug ,

especially

MDRepidemic

of

AIDSslack

offprevention

&treatmentlarge

group

of

latent

infectionWHO

declared

“emerging

state”

in

4-23,

1993WHO

declared

in

1995:

3-24

as

“Day

fortuberculosis

treatment

and

prevention”CutaneoustuberculosisBonetuberculosisLymph

nodetuberculosisRenaltuberculosisPulmonarytuberculosisepidermiology:inthe

world：infection:

1/3

popular，70%

in

Asiapatients:

20

million

(about

1%

of

infection

)ne tients

in

one

year:

9-10

milliondeath:

3

million

/yearin

China：infection:

0.

55

billionpatients:

6

milliondeath:

250

000

(1st)Mycobacterium

tuberclosisI.

Biological

propertiesMorphology

andstain:

slender

rod-shaped,Acid-

fast

stain

(Red,

see

next

slide).Much

particleCulture:(Lazy、greedy

and

stubborn)1) rich

nutrients:

egg

yolk,

potato,

glycerol,and

complex

organic

substances

(

malachitegreen

),

called

“Lowenstein

media”Acid-fast

staining

(Ziehl-Neelsen

method)thick

smear5%

carbol-fuchsion (heat,

5min)95%

alcohol

containing

3%

HCl

(decolor)methyl

blue

(1

min,

counter

staining)M.

Tuberculosisacid-faststainingResult

ofacid-fast

staining:

red

bacilli

in

blue

background3.obligate

aerobesgrowth

rate

is

much

slower:

doubling

time-18h,colony-2~4

weeks.grow

in

clumps

or

masses.sacids,

alkalis,

dehydration,

drug4.

Variationvirulence

---BCGdrug ,

even

MDRCauliflower-like,Off-whiteII.

PathogenesisIn

general:without

production

of

endotoxin

orexotoxin;type

Ⅳhypersensitivity---important

role1.

Constituents

of

Tubercle

bacilli:Lipid,

fatty

acid

and

wax

areresponsible

for

delayed

hypersensitivity2.PathogenicityToxic

factorcapsule(polysaccharides)

:CR3,TLRcord

factorphosphatidessulfatideswax

Dlipidsproteins

---Ab

for

diagnosistuberculin

sensitivityⅣ

hypersensitivityCord

formation

in

liquid

media(cord

factor)B.

Pathogenesis

&

PathologyTwo

Principal

Lesions(pathology)exudative

lesions:

bacilli,

PMN,

monocytesproductive

type:

central

area,

epithelioid

cells,fibroblasts,

lymphocytesSpread

oforganism

inthe

hostdirect

extension,

lymphatic

channel,

and

bloodstream,

bronchi

and

gastrointestinal

tracttuberclec.

Primary

&

post-primary

(secondary)

infectionsprimary

infection:

usually

in

childhood,exudative

lesion;caseation

and

calcifying

lymphnode;OT

test---+post-primary

infection

(reactivation):usually

inadults(bacilli

survived

inprimary

lesions)chronic

tissue

lesionsformation

of

tuberclescaseation

and

fibrosis后进入肺泡在肺泡巨噬细胞中繁殖出的菌体在肺泡内引起炎症-灶肺门淋巴

结（肿大）综合征5%发展成为活动性肺结核>90%经纤维化和钙化自愈淋巴管（炎）灶中潜伏的分枝杆菌外界的结核菌再次侵入抵抗力下降时繁殖干酪样坏死和空洞抗原呈递

细胞免疫

干酪样坏死病灶局限病灶中发生剧烈组织反应干酪样结节破溃导致空洞形成Primary

InfectionSyndromePrimary

focuslymphangitisTB

of

lymphonode

atporta

of

lungPrimary

InfectionSyndromeIII.

Immunity

and

hypersensitivityMainly

in

Cellular

immunity:

Tc

and

MφAb:

useful

gnosis?hypersensitivity?Relationship

of

Immunity

&

Hypersensitivity:infections

immunity;hypersensitivity.*Tuberculin

Test:material:

OT(old

tuberculin),

or

PPD-C

andPPD-BCGdose:

5

TU/0.1

ml

(1~250

TU)reaction:

time---48~72

h.induration

<5mm

->5mm

+>15mm

++interpretation:-:

never

been

infected

or

Immunity+:

infected++:

active

disease,

especially

in

childrenTuberculin

testPPD

injectedunder

skinIV.

Diagnostic

laboratory

testSpecimen:

sputum,

gastric

washings,

blood,

etc.Smear Acid-fast

stain(104~5/ml)Culture:

(102~3

/ml)DNA

or

IS6110

detection:

<10/mlAnimal

test:

Guinea

pigs(check

lymph

nodes)Antibodies:

?Chest

X-ray

of

patients

with

far-advanced

tuberculosisV.

Prevention

and

treatmentPrevention:BCG

inoculation.DNA

vaccine?Treatment:

specific

chemotherapy2

major

drugs-line

drugs(3)second-line

drugs(6)C.diphtheriaeI.

Biological

propertiesMorphology

and

stain:

club-shaped,Albert

staining

(body---blue,metachromatic

granules---black).Culture:1).

Media:

Loeffler’s

serum

media;blood;potasium

lurite---3

biotypesp.193Three

biotypes of

C.

diphtheriaeGravis

intermedius

mitisColony

sizebig,

grayblack

incenterblackStarch

fermentation+--hemolysis--+lurite

isreducedAlbert

stainingsmearAlbert’s

staining

solution

(5

min)Lugol’s

iodine

solution

(1

min)check

under

microscopeModel

figure

of

Albert

stainingResult

of

Albert

staining:

body

in

bluemetachromatic

granules

in

black3.s:not

strongto

dehydrationsensitivity

to

penicillin,

chloromphnic,

erythromycinII.

PathogenesisIn

general:spread

by

droplets

or

by

contactgrow

on

mucous

membranePathogenic

material:diphtheria

toxin---important

rolecord

factor2.

Diphtheria

toxin:produce

condition:

lysogenic

conversionFe+2---0.14~0.5µg/mlstructure:

as

following

figuretoxicity:

very

strong,

kill

one

cell/one

moleculeStructure

of

Diphtheria

toxinFragment

B:

38

kD,

bindingFragment

A:

24kD,

toxicityAction:

inhibit

polypeptide

chain

elongationEF-2

+

NAD

+

ADPR-EF-2

+

NA

+

H+EF-2: elongation

factor

2NAD:

nictotinamide

adenine

dinucleotideADPR:

adenosine

diphosphate-riboseNA:

nicotinamide

adenieSusceptible

tissue: heart

muscle,

adrenal

gland

,

liver,

…Disease:diphtheria---is

an

acute

respiratoryinfectous

diseaseilled

agethe

bacilli

grow

onmucous

membranepseudomembrane

toxin

blooddistanttoxic

damage

earlier

stage---prostration

and

dyspnealate

stage------heart

damagedropletpatiantshealth

carrierrecovering

carrierpharynx

nasalisproduceinvasivenesspseudomembranetoxincytotoxicity

(heart,

nerves…)SusceptiblesIII.

Immunityspecific

neutralization

anti-toxi