Intracellular pathogens

Question 1

What two cell types defend against viruses inside the cytoplasm?

Answer 1

NK cells (early) and CD8 cytotoxic T cells (later).

Question 2

What immune mechanism is required for intravesicular bacteria like Mycobacteria?

Answer 2

Macrophage activation by CD4 Th1 cells.

Question 3

Why is cell-mediated immunity essential for intracellular pathogens?

Answer 3

Pathogens are inside host cells → inaccessible to antibodies.

Question 4

What are NK cells derived from?

Answer 4

Common lymphoid progenitors (CLP) in the bone marrow.

Question 5

What cytokine do NK cells produce to enhance macrophage and T-cell responses?

Answer 5

IFN-γ.

Question 6

Why do NK cells act early in infection?

Answer 6

They provide immediate cytotoxicity before T cells expand.

Question 7

What prevents NK cells from killing healthy cells?

Answer 7

MHC class I engaging NK inhibitory receptors.

Question 8

What allows NK cells to kill virus-infected cells?

Answer 8

Infected cells lose MHC I (“missing self”), removing inhibition.

Question 9

What determines whether an NK cell activates or not?

Answer 9

Balance of activating vs inhibitory signals on the NK cell.

Question 10

Which NK activating receptor binds stress ligands like MICA, MICB, ULBPs?

Answer 10

NKG2D.

Question 11

Which NK receptors recognize pathogen-induced ligands?

Answer 11

NCRs (NKp44, NKp46, NKp30).

Question 12

Which NK subset is more cytotoxic?

Answer 12

CD56dim NK cells (higher CD16, stronger killing).

Question 13

Which NK subset produces more cytokines?

Answer 13

CD56bright NK cells (weaker CD16, stronger IFN-γ).

Question 14

What NK receptor mediates ADCC?

Answer 14

CD16 (Fc receptor) binding IgG.

Question 15

How do NK cells kill in ADCC?

Answer 15

Antibody-bound targets cross-link CD16 → NK releases cytotoxic granules.

Question 16

How does HCMV evade NK cell detection?

Answer 16

Retains NKG2D ligands intracellularly so NK cannot detect them.

Question 17

How does SARS-CoV-2 evade NK activation?

Answer 17

Downregulates activating ligands on infected cells.

Question 18

How do CMV and HSV evade CD8 T-cell recognition?

Answer 18

They inhibit TAP, preventing peptides reaching MHC I.

Question 19

What early cytokines appear during viral infection before T cell response?

Answer 19

Type I IFNs (IFN-α/β), TNF-α, IL-12.

Question 20

How are viral proteins prepared for MHC I presentation?

Answer 20

Degraded in the proteasome into short peptides.

Question 21

How do peptides enter the ER for MHC I loading?

Answer 21

Through the TAP transporter.

Question 22

What are the three required signals for activation of naïve CD8 T cells?

Answer 22

Signal 1: TCR–MHC I • Signal 2: Co-stimulation • Signal 3: Cytokines.

Question 23

Why are dendritic cells the most efficient at activating naïve CD8 T cells?

Answer 23

They express high B7, present antigen, and provide strong cytokine signals.

Question 24

What cytokine drives CD8 T-cell proliferation and differentiation?

Answer 24

IL-2, via the high-affinity IL-2 receptor.

Question 25

What forms the initial weak interaction between CD8 T cells and targets?

Answer 25

LFA-1 binding ICAM-1, allowing scanning.

Question 26

How does the CD8 T cell deliver its cytotoxic granules precisely?

Answer 26

Reorganizes cytoskeleton and MTOC toward the target.

Question 27

What are the four main cytotoxic molecules released by CD8 T cells?

Answer 27

Perforin, granzyme B, granulysin, serglycin.

Question 28

How does granzyme B trigger apoptosis?

Answer 28

It activates BID → tBID, causing mitochondrial permeabilization and caspase activation.

Question 29

What enzyme fragments DNA during intrinsic apoptosis?

Answer 29

CAD, released when ICAD is cleaved by caspase-3.

Question 30

How does Fas–FasL trigger apoptosis?

Answer 30

FasL binds Fas → recruits death domain proteins → activates caspase-8 → apoptosis.

Question 31

Why is CD8-induced cell death non-inflammatory?

Answer 31

Apoptotic cells expose phosphatidylserine, leading to silent macrophage clearance.

Question 32

How do intravesicular bacteria avoid killing inside macrophages?

Answer 32

They block lysosome fusion and prevent phagosome acidification.

Question 33

What two signals from Th1 cells activate macrophages?

Answer 33

CD40 ligand and IFN-γ.

Question 34

What antimicrobial mechanisms do activated macrophages use?

Answer 34

Reactive oxygen species (ROS), nitric oxide (NO), lysosomal enzymes.

Question 35

What structure forms when macrophages cannot fully eliminate bacteria?

Answer 35

Granuloma, with many Th1 cells surrounding infected macrophages.

Question 36

What cytokine recruits monocytes to infection sites during Th1 responses?

Answer 36

CCL2, produced after Th1–macrophage interactions.

Question 37

What cell type responses control intestinal helminths?

Answer 37

Th2 cells.

Question 38

What does IL-13 do in helminth response?

Answer 38

Increases mucus production & epithelial turnover to expel worms.

Question 39

What does IL-5 do in helminth defense?

Answer 39

Recruits eosinophils, which kill parasites via major basic protein.

Question 40

What cytokines create M2 macrophages in helminth infection?

Answer 40

IL-4 and IL-13.

Question 41

What cytokine is essential for mast-cell recruitment in helminth responses?

Answer 41

IL-3 and IL-9.

Question 42

What signals drive Th1 differentiation from naïve T cells?

Answer 42

IL-12 from DCs + IFN-γ from NK cells.

Question 43

What drives Th2 differentiation?

Answer 43

IL-4, often produced by basophils in response to helminth antigens.