Host Defense vs. Pathogen Offense - Ambrose

Question 1

Why do HIV + patients tend to experience GI complications?

Answer 1

Chronic inflammation as a result of HIV infection of CD4 Th cells leads to disruption of the gut epithelium and allows entry of enteric microbes.

Question 2

Tight junctions

Answer 2

Membranes between cells are pressed very closely together and bound by proteins.

Question 3

Desmosomes

Answer 3

Rivet-like cellular structure which acts to fasten cells into strong “sheets.”

Question 4

Gap Junctions

Answer 4

Membrane proteins that form a selectively permeable pore between cells. Allows cross-talk.

Question 5

Intrinsic responses to infection

Answer 5

Programmed cell death, autophagy, epigenetic silencing, host proteins, RNAi, CRISPRs

Question 6

Cellular process hijacked by some viruses to repress host gene transcription.

Answer 6

Epigenetic silencing via histone deacetylation. Transcriptional activators are unable to access DNA resulting in decreased txn.

Question 7

Example of a virus that utilizes epigenetic silencing during infection

Answer 7

HIV

Question 8

Host proteins capable of preventing viral infection or replication

Answer 8

Host restriction factors

Question 9

Host restriction factor that recognizes CpG dinucleotides and leads to degradation of viral RNAs.

Answer 9

ZAP

Question 10

Host restriction factor that acts as a cytidine deaminase to degrade viral DNA via hypermutation.

Answer 10

APOBEC3

Question 11

Pathogen recognition receptors present in endosomes which detect dsRNA, ssRNA, or CpG DNA

Answer 11

Toll-like receptors (TLR 3, 7, 8, and 9)

Question 12

Major txn factors activated by TLR signaling are

Answer 12

NF-kB, IRF3, and IRF7

Question 13

Pathogen recognition receptor which recognizes unique RNA motifs not present in host cytosol.

Answer 13

RIG-I

Question 14

Effector function of RIG-I signaling

Answer 14

Activation of MAVs to promote Type I IFN production

Question 15

ER-localized transmembrane protein which recognizes cytosolic dsDNA.

Answer 15

STING

Question 16

Effector function of STING signaling

Answer 16

cGAS binds cytosolic dsDNA and activates cGAMP. cGAMP binds to STING, translocating it to the golgi. STING activates TBK1 kinase which active IRF3 txn factor and induces IFN production.

Question 17

What do Type I IFNs do?

Answer 17

Stimulate macrophages and DCs. Stimulate NK-cell mediated killing.

Question 18

Consequences of IFN response

Answer 18

1. Activate cellular anti-viral genes
2. Sequester lymphocytes in the lymph nodes
3. Increase cytotoxicity of CTLs and NK cells
4. Upregulate MHC-I

Question 19

Examples of viral antibody evasion strategies:

Answer 19

1. Masking (antigen shedding)
2. Glycosylation
3. Antigenic shift
4. Cell-cell spread

Question 20

Examples of viral evasion of cell-mediated immunity

Answer 20

1. Disruption of MHC processing/presentation
2. Direct infection of immune cells