a eat ap: a a t eps Acinetobacter a

1
?????ß?a e?a?t??? a????p?? ????a? ??a t??
ep?ß??s??? Acinetobacter ?a? ? ????? ??????
?a????t?? Ge?????? ?. ?pa?t?p????? ?µ?µa
??s??e?t???? ?a?ep?st?µ??? ????????e????t??
?a?ep?st?µ?a??? ??T G?? ???
?eµes??,??p??? 2008
2
?????ß?a ?a? ???a ?µß?a ß??? pa????????
3
M????ß?a ?a? ?????p??
???? ???a µ????ß?a e??a?
p??t?te pa?????a
????? µ????ß?a e??a?
d???t??? pa?????a
?a pe??ss?te?a µ????ß?a
de? e??a? pa?????a
4
????? pa??????? st?? ???µ??e??

• ??apt??µ??e? ???e?
• ?????ß?a?? ?????da (e?d??e?e??) ??????
• ?e??ß????? (e???e?e??)
• ?p? a??pt??? / pt????
• ?e??ß????? (e???e?e??) ??????
• ?????ß?a?? ?????da (e?d??e?e??)

5
????e?e?? ???µ??e??

• ????? µe???e? d?aµat??? ta te?e?ta?a ?????a ????
• ?e?t??s?? t?? ?a????? ???e????
• ?µß???asµ??
• ?????aµµ?t?? e?????? ???µ??e??
• ?a?aµ????? se ??a?s? ?????? st?? a?apt?ss?µe?e?
  ???e?
• ??e?µ???a ?????t?ta?
• ??a?????? s??d??µa
• ?????s?a
• F?µat??s?

6
?ts? µ?????µaste ap? ta µ????ß?a
7
?????ß?a?? f??t?? t?? f?s?????????
µ????ß?a??? ?????da?

• ?e?????
  F??t??
• ??????? e????se?? 105/ml
• ?d??t??? p???a 1011/g
• S?e???
  108/ml
• St?µa??? 103/ml
• ?ept? ??te?? 104/ml
• ?a?? ??te?? 1011/g
• ???p???? e????se?? 109/g
• ????d???? ??st? lt103/ml
• ?e???e???t??? pe????? 106/cm2
• ???µa ????? pe?????? 103/cm2
  

8
? t???? t?? p???µ??

• It is said that one who knows the enemy and knows
  himself will not be endangered in a hundred
  engagements.
• ??t?? p?? ??????e? t?? e???? ?a? t?? ea?t? t??,
  de? ?a ???d????e? ??te se e?at? s?µp?????
• The combat of the victorious is like the sudden
  release of a pent-up torrent down a
  thousand-fathom gorge. This is the strategic
  disposition of force.
• ? µ??? t?? ????t? e??a? sa? t? ?????µa t??
  f???µat?? e??? ?e?µ????? se µ?a ?a??d?a ??????
  µ?t???. ??t? e??a? ? st?at????? d???es?? t??
  d??aµ??.
• Sun Tzu The Art of War

9
??? t?? ???t????µe ap? t??? µ???????a??sµ???

• ???? ap?fe????µe
• ?a?a?? ?e??, p??s?µ? ?e????, a?t??e?µ???? ?a?
  fa??s?µ??, ap?f??? t?? as?e???
• ???? p??eµ?µe
• ???s?a?? s?st?µa
• ???ß?µaste
• ??at?µ???? ?a? µ??a????? f?a?µ??
• ???s?µ?p????µe t?? e???fa?? µa?
• F??µa?a

10
???? ap?fe????µe
11
???S??
F?S??? ?? ??????
???????? ??????
G??s?a?? a??s?a
12
??? d???e?e? t? a??s?a?? s?st?µa

• ???s?e? ta pa?????a ?a? ta ?atast??fe?
  p??s????ta? ?a µ?? ?atast???e? ?a? t?? ea?t? t??
  (make the self/nonself discrimination)

13
??? a?t?µet?p??eta? ??a µ????ß?? ?ta? ?efe??e?
ap? t?? f?s??? a??s?a

• ?e t?? ep??t?t? a??s?a
• ?? a??s?a?? s?st?µa µp??e? ?a a?a?????se? ???e t?
  st? s?µpa? ?a? ßeßa??? t?? ea?t? µa?, t?? ?p???
  p??f???sse?. ??a??????e? ???e t? ???? ?a? t?
  ?atast??fe?.
• ? f?s??? a??s?a af??? ??a ta ??ta ?a? e??a?
  pa??????? t?? e??????? t?? ??t??
• ? ep??t?t? a??s?a af??? t? ?t?µ? ?a? e??a?
  pa??????? t?? e??????? (e???????s??) t?? at?µ??

14
?? t?e?? ??aµµ?? ?µ??a? ??a?t? t?? µ????ß???
???????? ??????
F?S??? ?? ??????
G??s?a?? a??s?a
15
? p??t? ??aµµ? ?µ??a?

• ???µa (F?a?µ??)
• ?p?de?µ?da (p???? 10-30 ??tt????)
• pH 3-5 (a?ast???e? t?? a??pt???)
• ?d??ta? - ??s???µ? (p??? ßa?t???a??? t????µat??)
• ?e?µ?da
• 15-40 f???? p?? pa??? ap? t?? ep?de?µ?da
• ?p?d????

• ???e? e?s?d?? t?? µ????ß???
• ?ept???
• S?e???
• ????? pe??ß?????
• ??ap?e?st???
• ??e??????ss?t? s?st?µa
• ?a???f??a
• ?????e???t???
• ???p???? e????se?? ????e? ?a? ?????de??
• ???a-????a

16
?? t?e?? ??aµµ?? ?µ??a? ??a?t? t?? µ????ß???
???????? ??????
F?S??? ?? ??????
G??s?a?? a??s?a
17
??dete??f??afa????tt???s?, ?a??t?s?, p???

• Fa????tt???s?-fa??s?µa 20 s
• NADPH Oxidase, O-2 ?a? H2O2, HO , ?3 ,
  Myeloperoxidase-Mediated Halogenation, ??
• ??d??? ?????a 20 s
• ??????f??a ?????a 20 s
• ?????a ?e?at???s??
• ??s?s?µata 5 min
• ?????t??? ?????a

Annu. Rev. Immunol. 2005. 23197223
18
?? fa????tta???? ??tta?a

• ? ?a??t?s? t?? µ????ß??? de? e??a? t? ?d?? µe t??
  fa????tt???s?
• ??s???f??a d???? ??a?t? pa??s?t??
• p??s?????ta? se a?t? ?a? ad?a??p????? ta ????µa
  t???
• ??tta?a f?s???? d???f???? ?atast??f??? µ???sµ??a
  ?a? ?a??????? ??tta?a
• ?atast??f??? t?? µeµß???? t???

19
? f?e?µ???d?? a?t?d?as?

• ????s? t?? ?e?µ???as?a?
• ?a e?e???p???µ??a µa???f??a e???????? interleukin
  -1, ? ?p??a d???ta? st?? e???fa?? p???a?e? a???s?
  t?? ?e?µ???as?a?
• ? p??et?? a?ast???e? t?? µ????ß?a?? a??pt???
• ? p??? ?????? p??et?? e??a? ß?apt????

20
???µ??? µe Aeromonas hydrophila

• Ascosfaera Apis
• ?????e? µe??ss??
• ?etaß??? t?? ?e?µ???as?a?
• Sa??a Diposaurus dorsalis ap? 38 se 40 ? C
• (Kluger et al 1975)
• ???s??a?? ap? 28 se 32.7?C
• (Covert and Reynolds 1977)
• ?????e? t?? ep?ß??s? ap? 25 se 67 ?a? ap?
  64 se 100, a?t?st???a ? t? ?d?? ?s??e? ?a? ??a
  p???? a??? e?d?

Hasday JD, Singh IS. Cell Stress
Chaperones(2000) 5 (5), 471480
21
?e??t???t?da ap? K pneumoniae 100 CFU K
pneumoniae St??e??? Caroli ??d?pe??t??a???
Te?µ???as?a ?e??ß?????t?? 35.5?C ?????a
3939.5?C
Te?µ???as?a ?e??ß?????t?? 23?C ?????a
36.537?C
Te?µ???as?a ?e??ß?????t?? 23?C ?????a
36.537?C
Te?µ???as?a ?e??ß?????t?? 35.5?C ?????a
3939.5?C
Hasday JD, Singh IS. Cell Stress
Chaperones(2000) 5 (5), 471480
22
?? t?e?? ??aµµ?? ?µ??a? ??a?t? t?? µ????ß???
F?S??? ?? ??????
???????? ??????
G??s?a?? a??s?a
23
?a ?eµf???tta?aa?a????????? ???a ????? ap? ta
a?t????a t?? ep?fa?e?a? t???
24
???????? ???S??

• ??e???t??? a??s?a-p??????µe?? ???es?
• ??at?µ???? ??se?? ??????s??
• ?eµfad??e?
• Sp???a?
• ?eµf???? ?st?? ß?e???????? (aµ??da???,
  ade??e?de?? e?ß?ast?se??, p???e? Payer ?a?
  d????t?? ?eµf???? ?st?? st? ß?e??????? t??
  e?t????)
• ?a??t??? a??s?a p??sf??eta? (p?a????ta?, ????
  -a??s?sfa????e?)

25
?a ??tta?a t?? e?d???? a??s?a?

• T ??tta?a
• a?a????????? ???a ????? ap? ta a?t????a t??
  ep?fa?e?a? t???
• APC pa???s?????? t? a?t????? sta ?eµf???tta?a ?a?
  s??e??????ta? st?? p???ap?as?asµ? ?a? st??
  a?t?d?as? t???
• Inducer
• ep?ß??p??? t?? a??pt??? t?? T ??tt????
• Helper
• p???d?t??? t?? a??s?a?? ap??t?s?
• ß?????? ta ? st?? pa?a???? a??s?sfa??????
• e?e???p????? ta µa???f??a p??? ?atast??f?
  e?d???tt????? pa???????
• Cytotoxic
• ????? ta µ???sµ??a ??tta?a
• Supressor
• te?e?????? t?? a??s?a?? ap??t?s?
• B ??tta?a (????µe 1011)
• ?a?????? a?t?s?µata/ a??s?sfa????e? (1014)

26
? a??s?a?? µ??µ??f?? µ??e? (primary response),
t? ??µ?ta? ??a p??ta (secondary response)

• ?? de?te?? f??? t? ???e? a????? se s??s? µe t??
  pa?a???? a?t?s?µ?t??
• ?a?e?a ?e?a??te?? pa?a???? a??s?sfa??????
• ??af??et???? t?p?? a?t?s?µa (a??s?sfa?????)
• ?e?t???????te?? a??s?sfa????? (higher binding
  strength)

27
?? 12 a?t?-a??s?a??? µ????ß?a??? µ??a??sµ?? I
Sex comes before disease (acquire virulence
genes), Sense environment and Switch virulence
genes on and off, Swim to site of infection,
Stick to site of infection, Scavenge nutrients
(especially iron), Survive stress, Stealth (avoid
immune system), Strike-back (damage host
tissues), Subvert host cell cytoskeletal and
signalling pathways, Spread through cells and
organs, Scatter
Cell 2006 124 767782
28
?? 12 a?t?-a??s?a??? µ????ß?a??? µ??a??sµ?? II
Sex comes before disease (acquire virulence
genes), Sense environment and Switch virulence
genes on and off, Swim to site of infection,
Stick to site of infection, Scavenge nutrients
(especially iron), Survive stress, Stealth (avoid
immune system), Strike-back (damage host
tissues), Subvert host cell cytoskeletal and
signalling pathways, Spread through cells and
organs, Scatter
Cell 2006 124 767782
29
? e?????? t?? a??s?a??? s?st?µat??
30
(No Transcript)
31
?? s?µµa??e? ta µ????ß?a t?? e?t????

• ??se?at?µµ???a µ???????a??sµ?? ???? st? ??te??
• ?? a????p??? s?µa ??e? 10p??s?? a???µ?
  ßa?t???d??? (1014) ap? ?t? e??a???t??? ??tta?a
  (1013).
• ?????ß?a t?? e?t????/ ??p????? 400 e?d?
  ßa?t???d??? (30 - 40 e?d? 99 )
• Bacteroides, Bifidobacterium, Clostridium,Enteroco
  ccus, Eubacterium, Fusobacterium,
  Peptostreptococcus, Ruminococcus, Lactobacillus
  and Escherichia
• Western lifestyle Lactobacillus
• Lactobacillus plantarum, Lactobacillus rhamnosus
  and Lactobacillus paracasei ssp paracasei
• GALT (Gut Associated Lymphocytic Tissue )
  a?t?p??s?pe?e? t? µe?a??te?? ?eµf???tta????
  s?st?µa t?? ???a??sµ??

32
THE MICROFLORA ORGAN
Gustafsson B 1985.The future of germ-free
research. Alan R. Liss. New York
33
?? t?e?? ??aµµ?? ?µ??a? ??a?t? t?? µ????ß???
F?S??? ?? ??????
???????? ??????
G??s?a?? a??s?a
34
G??s?a?? a??s?a?t? ap??t??ta? µe t?? ???s?-
???????µe?ta?
35
G??s?a?? a??s?a?t? ap??t??ta? µe t?? ???s?-
???????µe?ta?
36
G??s?a?? a??s?a?t? ap??t??ta? µe t?? ???s?-
???????µe?ta?
37
G??s?a?? a??s?a?t? ap??t??ta? µe t?? ???s?-
???????µe?ta?
38
G??s?a?? a??s?a?t? ap??t??ta? µe t?? ???s?-
???????µe?ta?

• ?µß???a
• ???s?sfa????e?
• ?.a.

39
G??s?a?? a??s?a?t? ap??t????e µe t?? ???s?-t?
?e?d?saµe
Subacute sclerosing panencephilitis (SSPE)
40
G??s?a?? a??s?a?t? ap??t????e µe t?? ???s?-t?
?e?d?saµe T??t?t?ta ap? ???µ??e?? st?? ???
Current Opinion in Critical Care 2004, 10250264
41
?? µe????? sta?µ??-?st???a

• Louis Pasteur (1822-1895)
• St?? 6/7/1886, eµß???ase t?? 9????? Joseph
  Meister µe a?t???ss??? eµß????, µet? ap? d????µa
  s????? µe ??ssa 2 µ??e? p???.
• ?? pa?d? ???se ?a? ?ta? µe????se ?ta? ? ???????
  t?? ?d??µat?? Pasteur.?? 1940, ?ta? ?? ?ata?t?t??
  Ge?µa??? t?? d??ta?a? ?a a????e? t?? ???pt? t??
  Pasteur t? a??????e ?a? a?t??t???se!!
• Robert Koch (1843-1910)
• ????a?a?, f?µat??s?, f?µat???a?t?d?as?
• ??µpe? 1905
• Emil Adolf von Behring (1854 1917)
• ?a??t?? t?? Koch. ?e t??? Kitasato ?a? Wernike
  a?a?????a? t?? d?f?e??d??? ?a? a?t?teta????
  a?t?t????? ??a ?e?ape?a
• ??aße?? ??µpe? 1901

42
?? µe????? sta?µ??-?st???a

• Paul Ehrlich (1854 1915)
• Te??e?a ??e?d???- ??e?da???? ??a ta
  a?t????a-a?t?s?µata
• ??aße?? ??µpe? 1908
• Elie Metchnikoff (1845-1916)
• ?e????af? t?? fa????tt???s??
• ??aße?? ??µpe? 1908
• Niels K. Jerne (1912-1994)
• ?? s?st?µa MHC ?a? ? ???µa?s? t?? ?a ??tta???
• ??aße?? ??µpe? 1984

43
?? µe????? sta?µ??-?st???a

• Susumu Tonegawa (b. 1939)
• ?????p???s? t?? ????d??? t?? a??s?sfa??????- ?
  p??????t?ta t?? a?t?s?µ?t??
• ??aße?? ??µpe? 1987
• Peter C. Doherty and Rolf M. Zinkernagel
• ? e?d???t?ta t?? ??tta????? a??s?a?
• ??aße?? ??µpe? 1996
• 1901-1996 11 ??aße?a ??µpe? ??a t? ???? t??
  a??s?????a?

44
?? µe???e? µ??e? ???????

• 1350 p.?. ? p??t? ?ata?e??aµµ??? ep?d?µ?a
• ? te?e?ta??? as?e??? ?ta? ? Ali Maakin st?
  S?µa??a, 26/10/1977
• ?f??e? ?s?ß?a a??s?a
• ? eµß???asµ?? ????se t?? 10? a???a st?? ???a ?a?
  staµ?t?se t? 1972
• ? G.Bush eµß????st??e to 1992!!

45
?? µe???e? µ??e? ???????-?µß???asµ??

• Lady Mary Wortley Montagu (1689-1762), S??????
  t?? p??sß? t?? ??eta??a? st? ???sta?t????p???
• ?µß???ase ta pa?d?? t?? t? 1717 ?a? 1721
• Edward Jenner (1749- 1823)
• ?µß???ase t?? 8????? James Phipps (1796) ?a? t??
  ??? t?? (1789).

Sarah Nelmes hand
46
?? µe???e? µ??e? ???????-?µß???asµ??

• Ga???p??ss???? ???eµ?? (1870-71).
•  
• T??at?? ap? t?? ep?d?µ?a ????????
• ? eµß???asµ???? Ge?µa????? st?at?? e??e µ??? 278
  ?e?????
• ? µ? eµß???asµ???? Ga?????? st?at?? e??e 23.400
  ?e?????

47
1521 3.500.000 e?at?µµ???a ??t???? p??a?a? ap?
e??????
How the Aztec Empire was defeated by the Spanish
In 1519, Hernando Cortes sailed to Mexico to
conquer the rich Aztec Empire. When Cortes and
his soldiers reached the capital of the Aztecs,
Moctezuma, their king welcomed Cortes as an
honored guest. Tensions mounted between the
Aztecs and the Spaniards. In the battle that
broke out, Moctezuma was killed. Soon after, the
Spanish were forced to retreat. Cortes returned
and began a siege of the city. Then, a smallpox
epidemic killed most of the Aztecs. The survivor
surrendered in 1521.
48
10 ?????a µet? ?a? ?? ???a? ap? e?????? ??asa?!!
How the Inca Empire was defeated by the Spanish
Francisco Pizarro and a small group of
conquistadors came to the Inca Empire in 1531.
There, a smallpox epidemic had killed many Incas.
Pizarro took advantage of the chaos in the
empire. He invited Atahualpa, the emperor, to a
friendly meeting and then had him imprisoned.
Atahualpa arranged for a ransom that added up to
almost 20 tons of gold and silver. This was said
to be the largest ransom in history. However,
Pizarro did not honor his end of the bargain. He
rejected the Inca ransom and ordered Atahualpa
killed, with that the Inca Empire was defeated.
49
?????ß?a e?a?t??? a????p?? ?? µe???e? µ??e?
The Black Death
The medieval pandemic that later came to be
called the "Black Death" killed an estimated
17-28 million Europeans (from 30 to 40 of the
total population) between the years 1347 and
1351 (1). Black Death was first reported in
Central Asia between 1339 and 1340, then in the
Genoese city of Caffa, where Black Death Mongol
cadavers were hurled as bacteriological weapons
over the city walls in 1346 (2). Epidemics
reached Europe when Genoese vessels docked in
Messina, Genoa, and Marseilles in November
1347. Yersinia pestis is considered to be the
most likely agent of Black Death, based mainly on
historical clinical records of bubonic and
pulmonary forms of the disease (3). However, as
the high levels of mortality and transmissibility
associated with the Black Death were not observed
during the third plague pandemic (4, 5),
alternative etiologies have been proposed.
Moreover, the spread of transmission of the
disease as well as the supposed densities of rats
and fleas made unlikely for several authors the
role of Y. pestis (5). The alternatives have
included the anthrax agent Bacillus anthracis,
the typhus agent Rickettsia prowazekii,
Mycobacterium tuberculosis, and hemorrhagic fever
(6-8). Confirmation of Y. pestis as the agent of
the Black Death would end this controversy and
improve our understanding of Y. pestis epidemics
in light of the current reemergence of this
infectious disease (9, 10).
50
?????ß?a e?a?t??? a????p?? ?? µe???e? µ??e?
The Black Death- t? ped?? t?? µ????
51
The triumph of death, Pieter Bruegel the elder
(1562)
52
?a?a??µ????ß??????a efa?µ???? se µe??te? ??a t??
Black Death

• S?????? de??µ?t??
• ??a???? p??f??
• ?????s? µe PCR

We believe that we can end the controversy
Medieval Black Death was plague. Raoult, et al.
2000
53
?????ß?a e?a?t??? a????p?? ?? µe???e? µ??e?
?a?d?µ?e? ???p?? t?? 20? a???a
1920 1940 1960 1980 2000
54
?????ß?a e?a?t??? a????p?? ?? µe???e? µ??e? t?
t???? µp??e st? µp?????? !
? e?????? pa???sµ???
55
??T ???µ??e?? a?µat??

• ??T G? ?e???s?a?
• Gram() 47
• Gram(-) 50
• ????te? 3
• Gram(-) 100
• Ps. Aeruginosa
• Kl. Pneumoniae
• E.Coli
• Acinetobacter B.
• Enterobacter

• ?a?. ??T G? ??? ????da
• Gram() 51
• Gram(-) 43
• ????te? 6
• Gram(-) 100
• Acinetobacter B.
• E.Coli
• Kl. Pneumoniae
• Providensia

??T ???µ??e?? a?ap?e?st????
56
???µ??e?? st? ??T Acinetobacter Baumani

• 1 st??? 2 as?e?e?? t?? ??T ?a pa???s??se? ???µ???
• 1 st??? 2 ?a pa???s??se? Gram (-) ???µ???
• 1 st??? 2 ?a pa???s??se? ???µ??? ap?
  Acinetobacter
• ?a? ap? t??? te?e?ta???? a?t??? t? 15 ?a
  ?ata???e?
• 25/05/008 -28/07/08 20 as?e?e?? (3)

57
? ???? ?at? t?? Gram () H ?st???a t?? ?a?e?t??
Fe????ß?ts ?????-G?ase??ts?? se 3 ß?µata

• G????s? (14/27/4-1877)
• T??at?? 11/06/1961
• ? ???µ? t?? 11/06
• ????µ?a ??a t?? ?e????????? t?? p??????? ???µ??e??

58
(No Transcript)
59
?e???? p???? ?a ????se?
60
?e???? p???? ?a ????se?
???a??st? ??a t?? p??s??? sa?