8. Early Host Response: Cell Autonomous and Innate

Which host defense is always present before infection occurs?

Intrinsic defenses.

Which defense layer includes NK cells and complement?

Innate immune system.

Which defense layer is pathogen‑specific and generates memory?

Adaptive immune system.

. Which intrinsic defense mechanism destroys viral RNA?

RNA silencing.

Which cells produce antibodies?

B cells.

Which immune defense take minutes/hours to develop

innate

critical events in acute infection

virus binds to epithelial cells —> replication and local spread

How do cells detect viral infection

c-type lectin receptors (CLRs)
Toll-like receptors (TLRs)
NLRs
Rig-like receptors (RLRs)

TLR2

recognizes lipoproteins, viral glycoproteins, and peptidoglycan

TLR3

recognizes double-stranded RNA, indicating viral presence.

TLR4

recognizes lipopolysaccharides (LPS) and viral glycoproteins

TLR7

recognizes single-stranded RNA, suggesting viral infection.

TLR 8

recognizes dsRNA, playing a role in antiviral responses.

TLR9

CpG DNA, unmethylated CpG oligos

Which adaptor proteins initiate the MyD88‑dependent TLR4 pathway?

TIRAP and MyD88.

What major transcription factor is activated downstream of MyD88?

induces NF-κB activation

What signaling cascades are triggered by MyD88?

Production of pro‑inflammatory cytokines.

What happens when a single PRR uses multiple adaptors?

produces distinct cellular outcomes because each adaptor activates different signaling pathways.

What happens when different PRRs use the same adaptor?

produce a common cellular response because they converge on the same signaling pathway.

RIG-1

retinoic acid-inducible protein 1 that detects viral RNA

MDA5

Function as helicases that detect foreign RNA in cytoplasm

MAVS

functions as an adaptor protein

MAVS activation drives

type I interferon (IFN‑α/β) production

What does cGAS detect?

Cytosolic dsDNA.

What molecule does cGAS produce after activation?

cGAMP.

What does cGAMP bind to?

STING.

Which kinase does STING recruit?

TBK1.

What transcription factor does TBK1 activate?

Activates IRF3 → induces NF-κB activation

Which apoptosis pathway is triggered by death receptors like Fas or TNF‑R?

Extrinsic (cell surface) pathway

Which pathway involves mitochondrial cytochrome c release?

Intrinsic (cytoplasmic) pathway.

Extrinsic Pathway to Apoptosis initiated by

binding of TNF, FASL, or APO2D/TRAIL to pro-apoptotic ligand

What structural change occurs during binding of TNF, FASL, or APO2D/TRAIL to pro-apoptotic ligand

trimerization.

1. Which caspases are considered effector (executioner) caspases?

Caspase‑3 and caspase‑7.

What prevents BAX/BAK from forming pores in healthy cells?

BCL‑2.

What event commits a cell to intrinsic apoptosis?

Mitochondrial outer membrane permeabilization (MOMP) by BAX/BAK.

What complex forms after cytochrome c binds APAF‑1?

The apoptosome.

Which caspase carries out the execution phase of intrinsic apoptosis?

Caspase‑3.

Necroptosis Pathways

Cell-induced form of programed necrosis

What triggers necroptosis instead of apoptosis?

Inhibition of caspase‑8.

Which proteins form the necrosome?

RIP1 and RIP3.

Is necroptosis inflammatory or non‑inflammatory?

Inflammatory, because the cell membrane ruptures.

Is necroptosis caspase‑dependent?

caspase‑independent.

Which viruses are susceptible to epigenetic silencing?

DNA viruses that replicate in the nucleus.

What is the main purpose of epigenetic silencing in antiviral defense?

To shut down viral gene expression and limit replication.

nonacetylated histones

silenced genes

acetylated histones

accessible genes

Interferons (IFN)

soluble molecules that activate antiviral

programs (interfere with viral infection)

Cytokines

soluble signaling molecules (proinflammatory

and anti-inflammatory)

Chemokines

Soluble mediators that chiefly influence the

migration of immune cells to sites of infection (chemotaxis)

What signaling pathway do IFN receptors activate?

The JAK/STAT pathway.

IFN induces

death of infected cells

How quickly are Type I IFNs produced after infection?

Within hours, declining after 10 hrs

IFN binding to IFN receptor leads to

synthesis of

>1000 cellular proteins

from interferon-stimulated genes (ISGs)

What induces tetherin expression in most cells?

Type I interferons (IFN‑α/β).

What type of viruses does tetherin block?

Enveloped viruses.

How does tetherin block viral release?

By physically tethering budding virions to the plasma membrane.

What proteins shut down the IFN response?

SOCS (Suppressors of Cytokine Signaling).

How do SOCS proteins inhibit IFN signaling?

They block JAK/STAT signal transduction

When are SOCS genes induced?

When IFN is present — part of a negative‑feedback loop.

Complement System

Enhances antibodies and phagocytes to clear infection

Natural Killer (NK) Cells

cytolytic lymphocytes

Dendritic cells (DCs) and Macrophages

sentinel cells; present viral peptides in lymph nodes

Neutrophils (and other granulocytes)

respond to initial cytokine burst

NK cells- secretion of cytokines (IFNγ and TNFα)

local inflammatory response, recruit adaptive immune cells

NK cells- secretion of perforin and granzymes

induce apoptosis

Neutrophils move to site of infection via

chemokine gradient

Neutrophil Extracellular Traps (NETs)

directly induced by PRRs recognizing virus particles

Which neutrophil PRR detects viral particles at the cell surface?

TLR4

Which PRRs detect viral ssRNA inside endosomes?

TLR7 and TLR8

Viral gene products- role in immune evasion

block IFN signaling or block B/T cell recognition