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

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Presentation transcript:

THE IMMUNE RESPONSES TO VIRUSES

Credit: Wikimedia Commons Course of a „classical” viral infection

Moresco EMY and Beutler B (2010) PNAS 107: ©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: Detection of viruses by intracellular receptors II. Endosomal Toll-like receptors Endosomal TLR activation induces type I IFN and inflammatory cytokine responses. TLR3 TLR7 TLR8 TLR9

Innate Immune signaling triggered by RNA viruses Michael Gale Jr. et al. (2005) Nature 436:

Oligomer accumulation in cytoplasmic membranes (e.g. ER) (Nucleus) (Cytoplasm) ISRE MxA MxA monomer MxA oligomer Trapped viral components (Nucleus) (Cytoplasm) ISRE OAS1 Inactive OAS1 monomer Induction by viral dsRNA Active OAS1 tetramer synthetized pppA(2’p5’A)n inactive RNaseL monomer active RNaseL dimer cleaved RNA (Nucleus) (Cytoplasm) ISRE PKR Inactive PKR monomer Active PKR dimer Induction by viral RNAs EIF2  P Inhibition of translation Establishment of the „antiviral state”: mechanism of action of Mx proteins, OAS1, and PKR

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

KINETICS OF VARIOUS ANTI-VIRAL MECHANISMS Complement AntibodyCytotoxic T cellsNK cells IFNα/β, IL-12 days level/activity VIRUS TITER

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

NK CELL DEGRANULÁCIÓ 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)