Theme 7: CTL Effector Mechanisms Flashcards
What is null selection?
T cells that do not recognize self-MHC molecules are deleted during maturation
What are NKT cells?
1) T cells that share similarities with NKCs and recognize CD1 molecules associated with lipids/lipid-bound molecules
2) Also has alpha/beta TCRs but is limited in diversity (also called iNKTs)
What is the main difference between primary vs secondary CTL responses?
1) In a primary response, IL-2 is released by Th cells to stimulate clonal expansion of CTLs
2) In a secondary response, activated memory CTLs release IL-2 in an autocrine fashion
What is the mechanism behind specificity of CTLs toward their target?
Specificity in targeting (such that no surrounding cells are harmed) is due to the formation of an immunologic synapse between the antigen-expressing target and the CTL - cytotoxic molecules are secreted into the synapse and does not diffuse to nearby cells
What are the steps to CTL-mediated killing ?
1) Antigen recognition on MHC I molecules
2) Activation of CTLs
3) Delivery of “lethal hit” (granule exocytosis to trigger apoptosis)
4) Release of CTLs (target cell death occurs during the next few hours, even after CTL dissociation)
Are cytokines and costimulator signaling required to initiate cytotoxic function of CD8+ T cells?
1) Cytokines and costimulatory signals are only required during intial activation/differentiation
2) When a CD8+ T cell becomes fully functional, they can kill any nucleated cell that displays that antigen without other signaling
What are the cytotoxic proteins contained within the granules of CTLs?
Granzymes (A, B, C), perforin, and serglycin
What is the function of granzymes?
They are serine proteases that cleave proteins after Asp residues
What is the function of perfornin?
It is a membrane-perturbing molecule homologous to C9 complement that facilitates delivery of granzymes into target by polymerizing to form aqueous pores in the target membrane
What is the function of serglycin?
Assembles complexes containing granzymes and perforin
What is a granule-independent mechanism of killing by CTLs?
FasL on activated CTLs binding to Fas receptors (death receptors) expressed on target cells, resulting in caspase activation and apoptosis
How do CD4+ T cells kill if they lack the same granules as CD8+ T cells?
FasL:FasR binding
How are CTLs not harmed when they target cells?
They express cathepsin B which is delivered to the CTL surface during granule release, degrading any cytotoxins that come into the vicinity of the membrane
What are 2 defence mechanisms by viruses to prevent cells from destroying microbes that infect them?
1) Can live and replicate in cells incapable of destroying microbes
2) During phagocytosis, microbes can escape from vesicles and live in the cytoplasm where microbicidal mechanisms are absent
What is a side effect that can occur from destroying infected cells?
Tissue injury, such as in hepatitis where infected liver cells are killed by CTLs and NKCs
