Cell Mediated Cytotoxicity - Diebel Flashcards
What effector molecules are produced by CD8+ cytotoxic T cells?
- Exhibits cytotoxicity (starts to produce perforin and granzyme)
- Expresses high affinity IL-2R(CD25)
- Synthesizes IL-2
- Expresses low levels of L-selectin and CCR7
- Express high levels of CD44 and LFA-1
- homing and retention at sites of inflammation
What effector molecules are produced by NK Cells?
- Express CD16 (FcγRIIIA)
- constant gamma chain receptor that recognizes IgG
- Lectin-like receptors (NKG2 family)
- binds to HLA-E and MHC Class I-like molecules (NKG2D)
- most are activating
- Immunoglobulin-like receptors (KIR = killer cell immunoglobulin-like receptors)
- bind to most MHC Class I molecules (HLA-A, B, C)
- most are inhibitory
How do CD8+ cytotoxic T-cells act to kill target cells (killing mechanisms)?
- Perforin and granzyme secretion:
- Performin molecules form pore on target cell membrane
- Ganzyme molecules activate apoptosis by cleavage of caspases
- Fas ligand protein on cell membrane surface:
- Membrane-bound FasL binds to Fas on the membrane of the target cells and initiates killing
- Activates apoptosis by cleavage of caspases
- CTLs can also kill by TNF production and secretion
How do NK cells act to kill target cells (killing mechanisms)?
- FasL expressed on the surface can kill cells expressing Fas
- Perforin and granzyme released from granules
- TNF expressed on the surface and secreted
What cell surface proteins of CD4+ T cells and APCs are important in the process of “licensing” the APC for cross-presentation of antigen?
- APC requires interaction with CD4+ Th1, Th17, OR direct interation with a pathogen - PAMP/TLR molecule
- CD4+ TCR must bind to APC’s MHC Class II
- CD28 binds CD80/86
- ***CD4+ CD40L must bind to APC’s CD40
- gives instructions to cross present
- CD4+ secretes IL-2
What cell is required to generate CD8+ memory T-cells?
CD4+ T cell
Do NK cells have memory?
They may?
Which specific NK cell KIR receptor and ligand are activating? (most KIR are inhibitory)
Activating: KIR2DS1 + HLA-C2
Which specific lectin-like NK cell receptor is inhibitory? (most are activating)
Inhibitory: CD94-NKG2A + HLA-E
How do NK Cells and CTLs complement each other?
- NK Cells:
- kill cells that mask the presence of foreign antigen on MHC Class I
- CTLs:
- kill cells that express foreign antigen on MHC Class I
How do CTLs bind to target cells in CTL killing?
- TCR-CD3 complex recognizes MHC Class I on target cell
- LFA-1 on CTL binds to ICAM on the target cell
- Antigen activation converts the LFA-1 from a low affinity state → high affinity state for better binding
- After about 5-10min, LFA-1 returns to low affinity state
- dissociation of CTL from target cell
How do NK cells recognize target cells for killing?
- recognition of an “altered self” state
- inhibitory receptors (KIR) recognize MHC class I alleles, which could explain why NK cells preferentially kill cells that possess low levels of MHC class I molecules
- Killing is determined by the balance of inhibitory and activating receptor stimulation
What are the effector cells involved with Antibody-Dependent Cell Mediated Cytotoxicity?
(Hint: 5 cells)
- NK cells
- Macrophages
- Monocytes
- Neutrophils
- Eosinophils
What is the general process of antibody-dependent cell mediated cytotoxicity (ADCC)?
- Effector cells bind to antigen via antibody (Fc receptor)
- Killing is mediated by cytolytic enzyme release by macrophages, neutrophils, and eosinophils
- TNF release by NK cells, monocytes, and macrophages
- Perforin release by NK cells and eosinophils
- Granzyme release by NK cells
What cytotoxic cells need to be educated in the thymus?
CD8+ T-cells (CTLs)
(NK cells do NOT need to be educated in the thymus)
