Virus -Host Interactions

List the common Viral Infections

Describe how Inflammation Integrates the Main Components of the Immune Response

Describe the Systemic Effects of Cytokines in Inflammation

• Liver Releases?

• Bone Marrow Releases?

Liver Releases:

• Iron, Zinc

• Acute Phase Proteins:

  • Mannose-binding proteins

  • Fibrinogen

  • C-reactive protein

  • Serum amyloid protein

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Bone Marrow Releases

• Colony-stimulating factors (CSFs):

  • Increase Hematopoiesis

  • Increase Lymphocyte mobilization

[REVEIW] Immune Responses Against Viruses

Describe Interferons Genes Expression in normal cells

• IFN genes not expressed in normal cells

  • Has repressor protein  -> inhibits IFN promotor

  • Trxn also requires activator proteins which bind to the un-repressed promoter and activate transcription.

Describe how pDCs are perfect in fighting Viruses

Plasmacytoid Dendritic Cells Ability to fight Viruses:

• Express High levels of all IFNS

• Very resistant to viral infections themselves

  • Allows them to escape viral immune evation

Describe Type III Interferons (IFN lambda) 

• Members

• Expressivity?

• Mech of Signals?

• Members:

  • IFNs lambda1: IL-29

  • IFNs lambda2: IL-28A 

  • IFNs lambda3: IL-28B

• Expressive:

  • Any nucleated cell type is able to express type III IFNs following infection with a virus.

  • Usually co-expressed w/ Type 1 IFNS 

• Mech of Signal

  • IFNs lambda signal via  heterodimer receptor pair independent of IFN a/b

    • Act. same intracellular signaling pathway -> redundancy

Draw out IFN signaling

Describe the steps “Setting up the “Antiviral State”

A key antiviral protein activated by the antiviral state is double- stranded RNA-activated protein kinase: pkr

1. What is the Schematic structure of dsRNA-activated protein kinase (pkr)

2. How do Viruses counter PKR.?

• encode proteins to circumvent the PKR activation process 

  • Antagonism of binding 

  • Inhibition

  • Blocking

1. Describe PKR receptor Mech pathway

2. How do Viruses counter this?

PKR receptor Mech:

• Absence of dsRNA Pkr -> inactive Monomer

• Binding of 2 or more Pkr monomers to dsRNA brings the catalytic domains (KD) into close proximity

• Cross-phosphorylation of KD occurs, -> altering conformation ->  phosphorylation of other substrates (eIF2a)

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How Viruses Counter this:

• Antagonism of Binding:

  • Prevents dimerizing

• Inhibition

  • Interfere w/ KD’s ability to associate

• Blocking

  • Blocks Cross-phosphorylation

What does Pkr do?

What does Type I/III Interferons do to counter viruses?

What does IFN gamma do?

List the Clinical Effects of IFNs

How do NK cells determine if a cell needs to die?

Describe Natural Killer Cells Mechanisms of killing virally-infected cells

Describe NK’s activation via ADCC and how its different from normal

List the ways Antibody can do Antiviral Activities