Host Response to Viral Infections

Question 1

Viral direct cell damage

Answer 1

direct cell damage and death may result from:

• diversion of cell’s energy
• shutoff of cell macromolecular synthesis
• competition of viral mRNA for cellular ribosomes
• competition of viral promoters and enhances for cellular factors
• inhibition of IFN defense

Question 2

Indirect viral cell damage

Answer 2

can result from integration of viral genome, induction of mutations in host genome, and host immune response.

Cellular immunity = clearing virus infection, humoral immunity=protect against reinfection

Question 3

Permissive vs. non-permissive cells

Answer 3

Permissive cell - provides machinery and components required for completion of viral replication

Non-permissive cell - does not.

Question 4

Intracellular restriction factors

Answer 4

block post-entry steps of certain virus infections - not adaptive but has specificity for certain viruses.

Trim5 blocks retroviruses
APOBEC blocks HIV and HCV
but Vif is an HIV protein that blocks APOBEC functioning

Question 5

TLR’s and RLH’s (Helicases)

Answer 5

recognize PAMPs on viruses and induce signals that activate innate immunity and starts development of acquired immunity.

Retinoic acid-inducible gene I (RIG-I) and–like helicases (RLHs) also help with this.

-TLR3 = dsRNA, 
TLR7 = viral RNAs and synthetic ligands (Imiquimod blocks this), TLR9 = unmethylated CpG.

Question 6

Type I IFNs

Answer 6

(alpha and beta) - antiviral cytokines transiently produced and secreted by most infected cels within hours of infection

Regulates transcription via ISRE (interferon-stimulated response elements)

Question 7

Type II IFN

Answer 7

gammaIFN

produced by T-cell and NK cells, more restricted than Type I.

Regulates transcription via GAS (gamma activated site)

Question 8

What pathway does IFN activate

Answer 8

IFN acts through receptors to signal through the Jak/Stat pathway to cntrol gene expression

Question 9

Describe the anti-viral state

Answer 9

(characteristic of cell that binds and responds to IFN)

Alters lots of transcription. Results in temp. blockage of cell proliferation, reduces cellular metabolism, potentiates NK cell activity (including IFNgamma prodution) and increases expression of antigen presentation molecules.

Question 10

Name major mediators of IFN-induced anti-viral state

Answer 10

1. ) PKR - protein kinase that phosphorylates and tehreby inactivates a cellular translation initiation factor resulting in decreased protein synthesis.
2. ) OAS - activates ribonuclease that degrades mRNA.

Question 11

What are the cells of the innate immune system and what do they do

Answer 11

1. ) Mononuclear phagocytes - phagocytosis, antigen present, inflammatory mediators
2. ) dendritic cells - present antigents to T-cells, stimulate B-cell differentiation and proliferation, secrete a LOT of antiviral and immunoreg. cytokynes (VERY IMPORTANT FOR INITIATING T-CELL RESPONSE TO VIRUS!)
3. ) NK cells - activate in response to IFNs or cytokines, CONTAIN the virus while T-cells CLEAR infection.
4. ) granulocytes - inflammatory cells do inflammatory things!

Question 12

Cytokines of the Innate defense

Answer 12

Important in viruses:

IFNs, IL-1, TNFalpha, IL-6, IL-12, IL-18

Question 13

Chemokines of the Innate Defense

Answer 13

Important in viruses:

IL-8, IP10, MIP1alpha

Question 14

Humoral response to viruses

Answer 14

B-cells are the effectors. Produce immunoglobulins. Antibodies produces during primary virus infections are lower affinity (are often IgM)

Question 15

Jobs of antibodies in viruses (specific types of antibodies lol)

Answer 15

IgA (secretory Ab) inhibits virion/host attachment, neutralizes toxins and enzymes -IgG inhibits fusion of enveloped viruses with host membranes

• IgG and IgM opsonize virions to enhance phagocytosis
• IgM can coat and agglutinate some virions
• IgG and IgM can facilitate complement lysis of enveloped viruses

Can also be group specific or type specific.

Question 16

Cell-mediated response

Answer 16

T-lymphocytes are effectors. T-cells bind to epitopes of host MHC class I or class II w/ viral antigen presenting on surface

Secrete IFNs, CTL’s lyse cells, NK cells and mactrophages kill cells directly or by antibody-dependent cell-mediated cytotoxicity (ADCC)

Th1 -> cell mediated immunity and inflammation
Th2-> humoral response

Question 17

Memory and secondary viral response

Answer 17

Protective immunity consists of preformed immune reactants (cells, Ab and cytokines) and immunological memory. Early reinfection=rapid clearing.

Later reinfection = immunological memory, leads to rapid increases in antobody and effector T-cells.

Question 18

How do viruses evade host defenses?

Answer 18

Antigenic variation (point mut. or antigenic drift)

Immune tolerance (mimicry or infection prior to competent immune system)

Restricted expression (latent infection, so invisible)

Production of viral molecules that act as decoys (proteins that mimic, sometimes release incomplete viral replicans as decoys)

Down-regulation of host proteins
Infection of immunoprivileges sites (brain lol)

Direct infection of immune system (HIV)

Inhibition of apoptosis/cell cycle control (often involved in tumorigenesis)