cientistas-encontram-fossil-de-tiranossauro-rex-gravida

http://oglobo.globo.com/sociedade/cientistas-encontram-fossilde-tiranossauro-rex-gravida-18899556

COO-

OH

COOOH

Biossntese de cido silico

Polisialiloligossacardeos

(a) Overall structure of NCAM on the cell membrane. The seven-domain protein binds to an identical NCAM
on the opposing membrane to form cell-cell junctions.
(b) (b) PSA-NCAM is modified with up to two linear polysialic acid chains, which are negatively charged

Funes biolgicas do cidos silicos

Exogenous Receptor

Endogenous
Receptor
Self

Self
= Oligosaccharide

*Pathogen, Toxin
or
Symbiont

O cido silico essencial vida

Funes biolgicas do cidos silicos

Exogenous Receptor

Endogenous
Receptor
Self

Self
= Oligosaccharide

*Pathogen, Toxin
or
Symbiont

(a) EXTRAVASAMENTO DOS LEUCCITOS

As Selectinas e seus alvos (molculas contendo acar) tornam

lenta a circulao de clulas sanguneas (1, 2), permitindo a entrada
destas clulas em tecidos injuriados (3, 4). A interrupo desta
ligao pode impedir o desenvolvimento de processos inflamatrios.

11

https://www.youtube.com/wa
tch?v=11bpptyfHkU

12

14

https://www.youtube.com/watch?
v=CJyM7eQrkEU

15

16

17

SIALIL LEWIS (SLeX)

Gal
OH

HO

OH

O
OH

HO
HO
NH HO

O
OH

O
O

O
HO

0O

H3 C
O

Neu5Ac

CH3

O
NH
H 3C
OH
OH

Fuc

HO
O

OH
O
O

OH

OH

Gal

O
HO

O-R
NH
H3 C

GalNAc

Entre 25% a 35% dos pacientes com cncer de seio ou clon ou tireide
ou gstrico sintetizam protenas com sialil Lewis X.
SLex ligam a selectinas presentes na superfcie de plaquetas e clulas
endoteliais.

Esta ligao possibilita que as clulas cancerosas se espalhem,

provocando metstase.

20

Na biossntese do sialil Lewis X necessrio um primer formado por duas

unidades de acares. Modificando esse precursor tem sido possvel, em modelos
experimentais, diminuir a expresso de protena contendo sialil Lewis X e
consequentemente uma menor ligao dessas molculas com selectinas e
plaquetas.

O
H3C

CH3
O

O
H3C

CH3
O

O
O

CH3

NH

O
H3C

H3C

(Ac6)GlcNAc13GalO-Naftalenometanol
AcGnG-NM

Funes biolgicas do cidos silicos

Exogenous Receptor

Endogenous
Receptor
Self

Self
= Oligosaccharide

*Pathogen, Toxin
or
Symbiont

23

24

26

cido Silico e evoluao?

27

Ajit Varki

28

29

Interaao com parasitas

especficos?

31

36

TRENDING Species that have more inflammation-soothing genes known as

Siglecs tend to live longer than species with fewer of the genes, a new
analysis shows.
39

41

42

Funes biolgicas do cidos silicos

Exogenous Receptor

Endogenous
Receptor
Self

Self
= Oligosaccharide

*Pathogen, Toxin
or
Symbiont

Papel do cido silico na interao

Trypanosoma cruzi
hospedeiro

Shedding vesicle

Sialoglycoproteins
Sialic acid acceptors
-O
-O O-O
-O
O-O O-O O-O O-

trans-sialidase

Neu5Ac

-O

N-glycan

T. cruzi
Glycocalix

-Gal
-GlcNAc

-Man

GIPL

-GlcNH2
m-Ins
2-AEP
http://www.fiocruz.br/chagas_eng/cgi/cgilua.e
xe/sys/start.htm?sid=13

-O

-O

O-

-O

OO-

N-glicana

-O

Neu5Ac
-Gal
-GlcNAc
-Man
-GlcN
m-Ins
2-AEP

-O O-O
-O
O-

-O

-O

-O

OO-

-O O-O
-O
O-

-O

-O

-O O-O
-O
O-

N-glicana

-O

O-

-O

OO-

-O

N-glycan

-O

-O

O-

-O

-O

-O

-O O-O
-O
O-

-O

O-

-O

OO-

-O

N-glicana

Trypanosoma cruzi trans-sialidase

H2O

Neu5Ac(2,3)-R

Sialidase
reaction

trans-sialidase

Neu5Ac

Galp -R
Transfer reaction

Neu5Ac(2,3)Galp R

TS activity is capable remodeling the T. cruzi cell

surface as well as host cell glycomolecules

Neu5Ac
-Gal

Alteration of cell surface sialylation

regulates antigen-induced naive
CD8+ T cell responses

Pappu BP, Shrikant P.A., J Immunol. 173: 275-84. 2004

PNA
-Gal
GalNAc
NeuNAc

T
Cell

CD8+ T cell activation

downregulates sialic
acid expression and
increases PNA binding
PNA binds to
Gal 1-3 GalNAc

T
Cell

Does T. cruzi uses its

trans-sialidase to manipulate
CD8+ T cell response favoring
host parasitism?

TS resialylates CD8+ T cells from T. cruziinfected mice

a) C57BL/6 nave mice

b) P. berghei infected C57BL/6 mice

c) BALB/c nave mice

d) T. cruzi infected mice treated with PBS

e) T. cruzi infected mice with aTS

100

101

102

103

104

PNA (Gal residues)

TS resialylates activated CD8+ T cells from

T. cruzi-infected mice

NeuAc residues
MAA-TRITC
MAA

Normal

Infected

TS/ infected

44.09

22.00

02.66

19.14

25.96

43.55

30.11

03.80

43.65

34.56

22.59

7.91

CD44-FITC
CD44-FITC
Activated T cells: CD44 high, PNA low

( PNA low = SA high= MAAhigh)

What is the Acceptor on CD8+ Cells?

Infection of ST3Gal-I (an enzyme required for sialylation of

core 1 O-glycans) deficient mice with T. cruzi partially
restores binding of anti-CD43 S7 mAb to CD8+ T cells
CD8+ T cell
uninfected WT mice

uninfected ST3Gal-I KO IgG control

uninfected ST3Gal-I KO

CD43
(sialylated core 1 O-glycan)

CD43 S7
binds to sialic acid containing
epitopes on CD43 core 1 O-glycans

T. cruzi infected
ST3Gal-I sialyltransferase KO
100

101

102

103

104

CD43 (S7)-FITC

CD43 is the acceptor for sialic acid

on CD8+ T cell

Activated CD8 T cells from T.cruzi

infected mice PNA high

Resialylated cells
PNA low

TS

Effectors
cell

T
Cell

T
Cell

Fetuin

T.cruzi peptide
IYNVGQVSI

target cell
CFSE
10mM

CFSE
1mM

Sialylation by TS decreases citotoxic activity of

antigen experienced CD8+ T cell in vitro
Sialylation of CD8+ T
cells by TS

CD8+ T cytotoxicity

Normal
60

Infected

Lysis %

Infected
Resialilated

N
INF
INFR

50

40
30
20
10
0
1:30

PNA (terminal Gal)

1:20

Cell rate

1:10

Sialylation by TS decreases citotoxic activity of antigen

experienced CD8+ Tcell in vivo
1,0 m M 10 m M

Normal
1,0 m M

Infected
10 m M

TS/ Infected

1,0 m M
10 m M

PNA (terminal Gal)

CFSE

PNA high

T
Cell

PNA low
trans-sialidase

T
Cell

Vrus Influenza

ESTRUTURA DO VIRUS INFLUENZA

Hemaglutinina
Neuraminidase

Stio Receptor

Regies
antignicas

Membrana

variveis

Protena M1

RNP:
Polimerase
Nucleoprotena
vRNA

Bicamada Lipdica
do envelope

Virions so normalmente aproximadamente esfricos com aproximadamente 200nm

de dimetro. O envelope contm "espigas rgidas" de hemaglutinina e neuraminidase
que formam um halo caracterstico de projees ao redor das partculas virais.

Mechanisms of viral entry into host cells

Essentials of Glycobiology
Second Edition

CLERA

Vibrio cholerae

ESTRUTURA CRISTALINA DA SUBUNIDADE B

(PENTAMERO) DA TOXINA DA CLERA LIGADA PORO
PENTASSACARDICA DO GM1

ESTRUTURA SIMPLIFICADA DA PORO

PENTASSACARDICA DO GANGLIOSIDEO GM1

O contato entre os resduos de aminocidos e a glicana se d atravs de

ligaes de hidrognio.

MECANISMO DE AO DA ENTEROTOXINA DA CLERA

TOXINA

Apresentao da
subunidade A

Ligao

Membrana

Adenilato
ciclase latente

Protenas G

Entrada da subunidade A

Dissociao
de A1 e A2
por reduo

A1 hidrolisa
NAD+

Nicotinamida
ADP-ribosilao da
protena G inativa
a GTPase, ativando
a adenilato ciclase

Adenilato ciclase ativa

O efeito final da toxina a

produo anormal de cAMP, que
estimula a mucosa a bombear
grandes quantidades de Cl- no
trato intestinal. H2O, Na+ e outros
eletrlitos so perdidos tambm
pela presso osmtica e pelo
gradiente eltrico causado pela
perda de Cl-. Assim, as clulas
danificadas pela toxina se tornam
bombas para gua e eletrlitos
causando diarria, perda de
eletrlitos e desidratao que
so tpicos da clera.

Helicobacter pylori

MECANISMOS DE ADERNCIA (ADAPTATIVOS) DE H. pylori

ADESO MUCOSA

Leb

H. pylori utiliza BabA (Y ) no

reconhecimento forte e
especfico do antgeno Leb.
SabA (V) tambm capaz de
ligar-se ao antgeno Leb

sLex
INFLAMAO CRNICA (GASTRITE)

BabA

SabA

Inflamao associada ao
antgeno sLex ().

STIO DE INFECO

Subclones sem expresso de

sLex escapam do contato com
linfcitos.

Leishmania

Clulas dendrticas humanas infectadas

ESTRUTURAS BSICAS DOS LPGS DE FORMAS

PROCCLICAS DE Leismania major E Leishmania donovani

INTERAO ENTRE LEISHMANIA E M VIA MOLCULAS

DE SUPERFCIE E PROTENAS SOLVEIS.

MACRFAGO

MACRFAGO