THE IMMUNE RESPONSES TO VIRUSES. Credit: Wikimedia Commons Course of a „classical” viral...
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Transcript of THE IMMUNE RESPONSES TO VIRUSES. Credit: Wikimedia Commons Course of a „classical” viral...
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THE IMMUNE RESPONSES TO VIRUSES
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Credit: Wikimedia Commons
Course of a „classical”viral infection
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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
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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
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Innate Immune signaling triggered by RNA viruses
Michael Gale Jr. et al. (2005) Nature 436: 939-940.
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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
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Michael Gale Jr. et al. (2005) Nature 436: 939-940.
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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
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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
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NK CELL DEGRANULÁCIÓNK CELL DEGRANULÁCIÓ
Antibody Dependent Cellular Cytotoxicity (ADCC)Antibody Dependent Cellular Cytotoxicity (ADCC)
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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)