A CTL forms an immunological synapse with a virus-infected cell and releases perforin-granzyme granules. The immediately adjacent uninfected cell is unharmed. What best explains why the neighboring cell is spared?
AGranzymes contain a viral peptide receptor that prevents them from entering uninfected cells
BDirected secretion into the synapse concentrates the granules precisely at the target cell membrane
CPerforin requires viral surface proteins to form pores, so it cannot insert into uninfected membranes
DThe Fas-FasL pathway actively signals neighboring cells to resist apoptosis
The CTL forms a tight junction (the immunological synapse) with its target and secretes granules directionally into that contact zone. This focused release means perforin and granzymes are deposited only at the target cell membrane, not dispersed into the surrounding tissue. There is no viral peptide receptor on granzymes, and perforin is a general pore-forming protein — the specificity comes entirely from the directional secretion mechanism.
Question 2 Multiple Choice
A patient carries a mutation that completely abolishes MHC class I expression on all nucleated cells. How would this most directly impair the adaptive immune response to an intracellular viral infection?
ACD8+ T cells could not be activated in lymph nodes because activation requires MHC-I on dendritic cells
BActivated CTLs could not recognize and kill virus-infected cells, because they survey MHC-I to detect intracellular peptides
CCD8+ T cells would be activated normally but could not release perforin-granzyme granules
DCD4+ T helper cells would compensate by directly killing MHC-I-deficient infected cells
CTL killing depends on the TCR reading viral peptides presented in the MHC-I groove on infected cells. Without MHC-I, infected cells are invisible to CTLs even after CTLs are fully activated. Note that DC-mediated activation of naive CD8+ T cells can occur via cross-presentation (MHC-I on the DC itself), so activation might proceed — but effector CTLs would then have no way to identify and kill peripheral infected cells, rendering the response ineffective.
Question 3 True / False
The directed secretion of perforin-granzyme granules into the immunological synapse ensures that CTL killing is confined to the cell in direct contact with the CTL.
TTrue
FFalse
Answer: True
This is the defining feature of CTL precision. The immunological synapse creates a sealed junction between the CTL and its target; granules are secreted into this confined space. The result is that only the contacted cell is exposed to lethal concentrations of perforin and granzymes, while neighboring cells are spared — a critical property for eliminating infected cells without causing widespread tissue damage.
Question 4 True / False
CD8+ T cells can become fully activated cytotoxic T lymphocytes through TCR recognition of peptide-MHC-I alone, without any requirement for costimulation.
TTrue
FFalse
Answer: False
Like all T cells, CD8+ T cells require two signals for full activation: TCR engagement (signal 1) and a costimulatory signal, typically B7-CD28 (signal 2). For many CD8+ responses to intracellular pathogens, CD4+ T helper cells also provide essential help by licensing the dendritic cell to deliver stronger costimulatory signals. TCR engagement alone induces tolerance or anergy, not activation — a safeguard against accidental autoimmune responses.
Question 5 Short Answer
Why does CTL-mediated killing specifically destroy the targeted infected cell without harming neighboring healthy cells, even though perforin is a general pore-forming protein that can insert into any lipid bilayer?
Think about your answer, then reveal below.
Model answer: Specificity does not come from perforin's chemistry but from where the CTL releases it. The CTL forms a tight immunological synapse with its target — a sealed contact zone between the two cells — and secretes granules directionally into this zone. Perforin and granzymes are confined to the target cell surface, where they form pores and deliver granzymes into the target cytoplasm. Neighboring cells are physically outside the synapse and receive negligible exposure. The killing mechanism is precise because of the anatomy of secretion, not because perforin is selective for infected membranes.
This question directly probes the key insight that the precision of CTL killing is a geometric property (directed secretion) rather than a chemical property of the effectors. Students who understand only that 'CTLs kill infected cells' without understanding the synapse mechanism would not be able to explain bystander sparing.