THE IMMUNE RESPONSES TO VIRUSES. Credit: Wikimedia Commons Course of a „classical” viral...

THE IMMUNE RESPONSES TO VIRUSES

Credit: Wikimedia Commons

Course of a „classical”viral infection

Moresco EMY and Beutler B (2010) PNAS 107:1261-1262.

©2010 by National Academy of Sciences

Detection of viruses by intracellular receptors I.RIG-I-like receptor (RLR) mediated type I IFN,

and cytokine/chemokine responses

Crozat K , and Beutler B (2004) PNAS 101:6835-6836.

Detection of viruses by intracellular receptors II.

Endosomal Toll-like receptors

Endosomal TLR activationinduces type I IFN andinflammatory cytokineresponses.

TLR3TLR7TLR8TLR9

Innate Immune signaling triggered by RNA viruses

Michael Gale Jr. et al. (2005) Nature 436: 939-940.

Oligomer accumulationin cytoplasmic

membranes(e.g. ER)

(Nucleus)

(Cytoplasm)

ISRE MxA

MxA monomer

MxA oligomer

Trapped viralcomponents

(Nucleus)

(Cytoplasm)

ISRE OAS1

Inactive OAS1 monomer

Induction byviral dsRNA

Active OAS1 tetramer

synthetized pppA(2’p5’A)ninactive

RNaseLmonomer

active RNaseLdimer

cleaved RNA

(Nucleus)

(Cytoplasm)

ISRE PKR

Inactive PKR monomer

Active PKR dimer

Induction byviral RNAs

EIF2 EIF2P Inhibition of

translation

Establishment of the Establishment of the „„antiviral stateantiviral state”:”:mechanism of action of mechanism of action of Mx proteins, OAS1, Mx proteins, OAS1, and PKRand PKR

Michael Gale Jr. et al. (2005) Nature 436: 939-940.

napok

vírus-titer

2 4 6 8 101 3 5 7 9 1211 13

KINETICS OF VARIOUS ANTI-VIRAL MECHANISMS

Complement

AntibodyCytotoxic T cellsNK cells

IFNα/β, IL-12

days

lev

el/a

cti

vity

VIRUS TITER

APC

CD40

M HC II

TNFIFN

CD8+

Tc

IL-12

CD4+

T 1H CD40LCD40L

CD40 B

Ag

Apoptotic cell

LINKED RECOGNITION OF VIRAL ANTIGENS BY CD4+ AND CD8+ T LYMPHOCYTES

M HC I

CROSS- PRESENTATION

Survival IL2 IL4 IFN

NK CELL DEGRANULÁCIÓNK CELL DEGRANULÁCIÓ

Antibody Dependent Cellular Cytotoxicity (ADCC)Antibody Dependent Cellular Cytotoxicity (ADCC)

ESCAPE MECHANISMS OF VIRUSES

High variability of surface antigens

Integration to the host cell genome

Infection of „privileged” locations

Inhibition of antigen presentation (HSV – TAP, HCMV- MHC-I)

Production of cytokin receptor homologes (HCMV- chemokine, poxvirus- IFN)

Immunosupresszive cytokine production (EBV - IL-10 homolog)

Infection of immunocompetent cells (HIV)