inmunidad innata 2013

Mecanismos especficos de reconocimiento

en la respuesta inmune innata

Cintica de respuesta adquirida

durante una infeccin

La respuesta inmune La respuesta a un

contacto inicial ocurre en tres fases:

Las primeras dos requieren reconociemiento asociados a patrones de reconocimiento asociado a la lnea germinal

Inmunidad Innata Immunidad Adptativa

rpida (minutos a horas) lenta (4-7 das)

varios receptores TCR, Ig

asociada a la lnea germinal recombinacin gentica

distribuda ampliamente distribucin limitada

MF, DC, PMN, NK Clulas B y T

no-clonal clonal

sin memoria immunolgica memoria inmunolgica

Contrastes entre la inmunidad innata y adaptativa

Los cdigos de reconocimiento para diferenciar entre lo propio y lo no propio: carbohidratos (el cdigo de barras)

Glicoconjugados

A: Porcin glicano

B: Porcin aglicona

A

B

Glicoprotena

A

B

Glicolpido

OH H

HN H

CH2

H

O H

H

H

H O

HO

O

H

H

H

H

H H

H

H H

H

H H H

H

H

H H H H

H

H

HO OH

OH

O

O

OH O

O

O

O O

O

O

O NH

C CH3

CH2OH CH2OH

CH2OH

CH2OH

H2C

HO

OH

OH NH

OH

C O

CH3

NH4 C OH

OH

+ -

O

Proceso de glicosilacin en eucariotes

Mecanismos de glicosilacin en procariotes

O

O NH

H

N

O

NH HO

HO

O

O

HO

HO NH

O

O O

O HO

O

O

O O

O

O O

O

O

O O

O

O

O O

O

O

O

O

O

O

O

HO

HO HO

HO

HO HO

HO HO

HO HO

OH

HO HO

HO

HO

HO

OH

HO

OH OH

OH

HO

HO HO HO

HO

HO

OH

OH

OH

HO

OH OH

OH

OH

OH

O

CH

2 OH

H

H

H

H

H

NH

Ac

OH

O

N H

C

C

C

O

H2

NH H CO NH CO NH CH CH2

CH2

OH

CO

N-glicosilacin

Esquema de la O-glicosilacin

Ser/Ser/ThrThr

Ser/Ser/ThrThr Ser/Ser/ThrThr

Ser/Ser/ThrThrSer/Ser/ThrThr

Ser/Ser/ThrThr


antgeno Tn

Antgeno sialyl Tn

6

antgeno T

6

Antgeno disialyl Tn

Core 1 GalT

ST6GalNAc-I ST6GalNAc-II

(ST6GalNAc-I)

Core 2 GalNAcT

ST3Gal-I

(ST3Gal-II)

(ST3Gal-IV)

ST6GalNAc-III

ST6GalNAc-IV

(ST6GalNAc-I)

(ST6GalNAC-II)

Ser/Ser/ThrThr

(n)

Ser/Ser/ThrThr



Ser/Ser/ThrThr


antgeno Tn

Antgeno sialyl Tn

6

antgeno T

6

Antgeno disialyl Tn

Core 1 GalT


(ST6GalNAc-I)

Core 2 GalNAcT

ST3Gal-I

(ST3Gal-II)

(ST3Gal-IV)

ST6GalNAc-III

ST6GalNAc-IV

(ST6GalNAc-I)

(ST6GalNAC-II)

Ser/Ser/ThrThr



Ser/Ser/ThrThr


Ser/Ser/ThrThrSer/Ser/ThrThrSer/Ser/ThrThrSer/Ser/ThrThr

Ser/Ser/ThrThrSer/Ser/ThrThrSer/Ser/ThrThr Ser/Ser/ThrThrSer/Ser/ThrThrSer/Ser/ThrThrSer/Ser/ThrThr

Ser/Ser/ThrThrSer/Ser/ThrThrSer/Ser/ThrThrSer/Ser/ThrThrSer/Ser/ThrThrSer/Ser/ThrThrSer/Ser/ThrThrSer/Ser/ThrThrSer/Ser/ThrThr

Ser/Ser/ThrThrSer/Ser/ThrThrSer/Ser/ThrThrSer/Ser/ThrThr

Ser/Ser/ThrThrSer/Ser/ThrThrSer/Ser/ThrThrSer/Ser/ThrThrSer/Ser/ThrThr Ser/Ser/ThrThrSer/Ser/ThrThrSer/Ser/ThrThrSer/Ser/ThrThrSer/Ser/ThrThr

antgeno Tn

Antgeno sialyl Tn

6

antgeno T

6

Antgeno disialyl Tn

Core 1 GalT


(ST6GalNAc-I)

Core 2 GalNAcT

ST3Gal-I

(ST3Gal-II)

(ST3Gal-IV)

ST6GalNAc-III

ST6GalNAc-IV

(ST6GalNAc-I)

(ST6GalNAC-II)

Ser/Ser/ThrThr

(n)

Ser/Ser/ThrThrSer/Ser/ThrThrSer/Ser/ThrThrSer/Ser/ThrThrSer/Ser/ThrThr

(n)(n)

GalNAc

cido Silico

Gal

GlcNAc

Fuc

GalNAc

cido Silico

Gal

GlcNAc

Fuc

H

N

O

NH HO

HO

O

O

HO

HO NH

O

O O

O HO

O

O

O O

O

O O

O

O

O O

O

O

O O

O

O

O

O

O

O

O

HO

HO HO

HO

HO HO

HO HO

HO HO

OH

HO HO

HO

HO

HO

OH

HO

OH OH

OH

HO

HO HO HO

HO

HO

OH

OH

OH

HO

OH OH

OH

OH

OH

O

O NH

Estructuras de oligosacridos marcadores de identidad (Los grupos sanguneos)

Innate immunity mechanisms Recognition (self/non-self)

Soluble

Lectins, LBP, PGBP

Membrane-associated receptors

NK cell, homing, scavenger, complement, TLRs, etc

Intracellular

NODs

Signaling

TLRs

NODs

Effector functions

Soluble

Complement, lysozyme, antimicrobial peptides

Membrane-associated

Nramp

Intracellular

Oxidative burst

C1q

Lectins

(MBL, ficolins

lung surfactant)

Pentraxins

(CRP, SAP)

Soluble Receptors

Mammalian Innate Immune Receptors

Selectin

C1q

Lectins

(MBL, ficolins

lung surfactant)

Pentraxins

(CRP, SAP)

Soluble Receptors

C

C

C

C

C

DC-SIGN MF-MR

C-type Lectin Membrane Receptors

PM


Selectin

C1q

Lectins

(MBL, ficolins

lung surfactant)

Pentraxins

(CRP, SAP)

Soluble Receptors

C

C

C

C

C

DC-SIGN MF-MR



KIR2DL3 NKGA NITR

ITIM

ITIM

ITIM

ITIM

J

NK Cell Receptors

ITIM

ITIM

C2

C2 V/C2

CL V

PM

Selectin

C1q

Lectins

(MBL, ficolins

lung surfactant)

Pentraxins

(CRP, SAP)

Soluble Receptors

C

C

C

C

C

DC-SIGN MF-MR



CD-36 CD68 SR-A

Scavenger Receptors

KIR2DL3 NKGA NITR

ITIM

ITIM

ITIM

ITIM

J

NK Cell Receptors

ITIM

ITIM

C2

C2 V/C2

CL V

PM

Selectin

C1q

Lectins

(MBL, ficolins

lung surfactant)

Pentraxins

(CRP, SAP)

Soluble Receptors

C

C

C

C

C

DC-SIGN MF-MR



CD-36 CD68 SR-A

Scavenger Receptors

Complement Receptors

CR3 CD14 FcR

KIR2DL3 NKGA NITR

ITIM

ITIM

ITIM

ITIM

J

NK Cell Receptors

ITIM

ITIM

C2

C2 V/C2

CL V

PM

Selectin

C1q

Lectins

(MBL, ficolins

lung surfactant)

Pentraxins

(CRP, SAP)

Soluble Receptors

LRR

NOD-2

NBS

CARD

NBS

CARD

CARD NOD-1

Intracellular Receptors

C

C

C

C

C

DC-SIGN MF-MR


TIRAP

MyD

88

TRIF

NF-kB

Immune response

genes


CD-36 CD68 SR-A

Scavenger Receptors

Complement Receptors

CR3 CD14 FcR

KIR2DL3 NKGA NITR

ITIM

ITIM

ITIM

ITIM

J

NK Cell Receptors

ITIM

ITIM

C2

C2 V/C2

CL V

PM

Toll-like Receptors

CD14

TIR

LBP

MD-2

Specificity of Toll-Like Receptors

PM TIR TIR TIR TIR TIR TIR TIR TIR TIR TIR

1 2 3 4 5 6 7 8 9 10

LP PG

LP

dsRNA

LPS Flagellin Zym

LP

(?) (?) CpG

CpG (?)

Domain Structure of C-type Lectin Subunits

C RD Cys-rich Collagen-like

EGF-like

Domain

(var. number)

C RD Complement- binding

Domain

(var. number)

Trans-

membrane

Domain

MBL

Roles of C-Type Lectins in Innate Immunity

Direct interaction with microbes

opsonins

macrophage



opsonins

macrophage



opsonins

cell surface receptors

macrophage

FMR



opsonins

cell surface receptors

macrophage

FMR

bacterium

Figure 2-5 part 1 of 2

Figure 2-5 part 2 of 2

Complement Pathways

C3

Classical Pathway Alternative Pathway

Ab-antigen

C1qrs

C2

C4

C3-H2O

Factor D

Factor B

C3 convertase

Phagocytosis Lytic pathway

Roles of Lectins in Innate Immunity

Complement Pathways

C3

Classical Pathway Lectin Pathway Alternative Pathway

MASP

C2

C4

Ab-antigen

C1qrs

C2

C4

C3-H2O

Factor D

Factor B

C3 convertase

Phagocytosis Lytic pathway

Roles of Lectins in Innate Immunity

MBL

Interfase entre la inmunidad Innata

y Adaptativa

C3b, C5b

Interfase entre la inmunidad Innata y Adaptativa

C3b, C5b

PMN


y Adaptativa

C3b, C5b

Macrophage

PMN

TLRs

MF-MR


y Adaptativa

C3b, C5b

Macrophage

PMN

+ + x

NK

Target cell

TLRs

MHC

CD94 NCR-L

NCR

Ly49H

MF-MR


y Adaptativa

C3b, C5b

Macrophage

PMN

+ + x

NK

Target cell

TLRs

MHC

CD94 NCR-L

NCR

Ly49H

MF-MR

Pathogen destruction

Effector function


Effector function


y Adaptativa


y Adaptativa

C3a, C5a


Effector function Macrophage

PMN

IFN- IFN-

+ IFN-g

+

Dendritic

Cell +

+ + x

NK

Target cell

TLRs

TLRs

MHC

CD94 NCR-L

NCR

Ly49H


Effector function

MF-MR

C3b, C5b



PMN

IFN- IFN-

+ IFN-g

+

Dendritic

Cell +

+ + x

NK

Target cell

TLRs

TLRs

MHC

CD94 NCR-L

NCR

Ly49H


Effector function

MF-MR


y Adaptativa

C3b, C5b



PMN

IFN- IFN-

+ IFN-g

+

Dendritic

Cell +

+ + x

NK

Target cell

TLRs

TLRs

MHC

CD80

CD86

CD40

MHC

CD94 NCR-L

NCR

Ly49H


Effector function

MF-MR

Interfase entre la inmunidad

Innata y Adaptativa

C3a, C5a



PMN

IFN- IFN-

+ IFN-g

+

Dendritic

Cell +

+ + x

NK

Target cell

TLRs

TLRs

MHC

CD80

CD86

CD40

MHC

CD94 NCR-L

NCR

Ly49H


Effector function

MF-MR


Innata y Adaptativa

C3b, C5b

Destruccin patgeno

Funcin efectora Macrophage

PMN

IFN- IFN-

+ IFN-g

+

B Cell

T Cell

Dendritic

Cell +

+ + x

NK

Target cell

TLRs

TLRs

MHC

CD80

CD86

CD40

MHC

CD40

TCR

CD28

CD40L

CD40L

CD94 NCR-L

NCR

Ly49H

Destruccin patgeno

Funcin efectora

MF-MR


Innata y Adaptativa

Destruccin patgenos

C3a, C5a

Destruccin patgenos

Funcin efectora Macrophage

PMN

IFN- IFN-

+ IFN-g

+

B Cell

T Cell

Dendritic

Cell +

+ + x

NK

Target cell

TLRs

TLRs

MHC

CD80

CD86

CD40

MHC

CD40

TCR

CD28

CD40L

CD40L

CD94 NCR-L

NCR

Ly49H

Destruccin patgenos

Funcin efectora

Funcin Efectora

Inmunidad Memoria

MF-MR


y Adaptativa

Los carbohidratos funcionan como seales de interaccin clula-clula


Recognition of endogenous ligands

Rolling adhesion

(selectin binding)

Tight adhesion

(integrin activation)

leukocytes

epithelial

cells

Extravasation

L-selectin integrin

integrin

adhesion

molecule

selectin

adhesion

molecule

La familia del cido silico

Sialectinas

La familia de SIGLECS

Relacin de estructuras O-glicosiladas y apoptosis

Amado et al., J Biol Chem. 2004;279:36689-97.

Y los receptores de Ashwell-Morell ?

Lectin receptors mediating cooled platelet clearance

Colectinas

Colectinas que participan en la respuesta inmune innata

TLR modulation of phagocytosis

A) TLRs may be phagocytic receptors B) TLR signaling may modulate activation of other phagocytic receptors. C) TLR signaling may regulate the rate at which phagosomes mature into phagolysosomes. D) TLR signaling may induce or inhibit production of proteins required at all stages of phagocytosis.

Receptores de colectinas

Fimbria de E. coli Tipo 1

Carbohidratos como mecanismo de reconocimiento por bacterias

Adhesin de Mannheimia haemolytica a clulas traqueales bovinas

Gal-4 and Gal-8 are expressed by the intestinal epithelium and each have

CRDs (left). Galectins can tightly bind blood group B carbohydrates, which

some bacteria express on the side chains of surface lipopolysaccharides.

Upon binding of either of these lectins (middle), bacteria rapidly lose

viability. Surface blebs appear as the bacteria are killed. Nat Med. 16 (2010) 263-4.

El rubulavirus porcino LPM

Mecanismos de patogenia

Rubulavirus en Bulbo Olfatorio

Y ahora quien podr salvarnos.

Alteraciones de la glicosilacin asociadas a defectos genticos. Enfermedad Alteracin en la glicosilacin Manifestacin clnica

Fibrosis qustica Expresin de a1,3 fucosil transferasa, Poliposis nasal, tos, fiebre Sulfoniltransferasas, MUC2 y pancreatitis, disfuncin MUC5AC. heptica, infecciones respiratorias recurrentes por P. aeruginosa

Sndrome de Exceso en la O-glicosilacin de CD43 Inmunodeficiencia severa Wiskott Aldrich por aumento en la expresin de otitis media, eccema, b 1, 6 N-acetil glucosaminil petequias, linfadenopata, transferasa. esplenomegalia, anemia.

Nada es verdad.

inmunidad innata 2013

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