Exam 2 (Lecture 13) - GD, NKs, And Response to Viruses Flashcards
Explain what a gamma-delta T cell is and its role in the immune response.
Contains gamma delta T cell receptor (different AA sequence than alpha-beta T cell)
Has CD3 receptor (function is in between innate and adaptive, many are intraepithelial lymphocytes).
Role in immune response: Found on mucosal surfaces and important for protection at these sites
Some secrete cytokines, some are cytotoxic
Describe, in general terms, how apoptosis is induced and what happens in a cell that is induced to undergo apoptosis.
NK Cells and CTL induce apoptosis
Intrinsic and extrinsic pathways:
- Intrinsic:
- Intrinsic granzymes initiate cell breakdown
protein cleavage or activation of endonucleases
which cause DNA damage and clumping of
chromatin
- Formation of apoptotic bodies
- Phagocytosis of apoptotic bodies
- Extrinsic:
- Fas/FasL binding (CD95/CD95L; death receptor)
or TNF receptor
Explain the differences between apoptosis and necrosis and give examples of cells in the immune system responsible for inducing each.
Necrosis:
- Uncontrolled cell death
- Membrane degrades
- Cytoplasmic contents released = inflammation
- Larger area involved
- Neutrophils and macrophages
Apoptosis:
- Programmed cell death
- Membrane intact = no inflammation
- Not much tissue damage, membrane-bound
blebs are phagocytose and digested
- Individual cell or clusters of cells
- NK Cells and CTLs
List 3 mechanisms that cytotoxic T cells (CTLs) use to kill target cells. For each, include the molecules and functions involved - for binding and killing.
1) Perforin and granzyme pathway:
- CTL granules contain perforin and granzyme
- Perforin: polymerizes and forms pore in target
cell membrane
- Granzyme: enters cytosol through the perforin
pore and activates the intrinsic apoptotic
pathway (caspase cascade)
2) TNF > TNF Receptor
- TNF secreted from CTLs
- Receptor mediated activation of caspase
cascade and apoptosis
3) CD95 (Fas ligand) > CD95 Receptors
- Fas receptor = death receptor pathway
- CTLs express Fas ligand in their membrane and
binding to Fas (from nucleated cells) leads to
activation of extrinsic apoptotic pathway
- Activation of caspase cascade and apoptosis
Describe how an NK cell recognizes a cell to kill and describe the killing mechanisms of the NK cell.
1) Abnormal MHC I presentation
- if no inhibition from MHC I, cell is recognized by
NK cell for death
2) Binding to MICA stress molecules on a cell
3) ADCC
- antibody dependent cell mediated cytotoxicity
- NK cell has Fc receptors to bind to Ab bound to
tissue cells
- releases granzymes and perforin to kill cells
- activates intrinsic apoptotic pathway = apoptosis
4) Perforin/granzyme pathway
5) TNF receptor on target/TNF
6) Fas/Fas ligand binding (death receptor pathway)
Explain how the CTL and NK cells are complementary, including timing, targets, and the benefit to the host to have both cell types.
Complementary:
- Work together to kill a cell they target
Timing:
- NK cells: work immediately (innate)
- CTLs: take time to work (adaptive)
Targets:
- NK cells: cells with absence or decreased
expression of MHC I, MICA stress molecules on a
cell, antibody coated cell
- CTL: cells with peptide antigen on MHC I
Important for protection from intracellular pathogens and cancer.
- NK cells work immediately during primary
response so CTLs have time to clonally expand
- if a pathogen blocks presentation of peptides on
MHC I, CTLs can’t respond, but NK cells will kill
the cell(s) with abnormal MHC I presentation
Compare and contrast the various killing mechanisms used by the immune system.
- NK Cells/CTLs
- Perforin/granzyme pathway
- TNF receptor on target/TNF (induces apoptosis)
- Fas/FasL binding (CD95/CD95L) (apoptosis)
- Neutrophils
- Lytic enzymes and antimicrobial peptides from
granules (lysozyme of defensins) - Oxidative metabolism
- Neutrophil Extracellular Traps (NETs)
- Macrophages
- Nitric Oxide
List 2 parts of the innate immune response and two parts of the adaptive immune response important for protection against viruses.
Innate:
- interferons
- complement
- NK cells
Adaptive:
- CTLs
- Antibodies
Explain the mechanism of action of Type 1 interferons, where they come from, and explain their role in immunity.
Binds to interferon receptors which stimulate cells to produce enzymes that:
- inhibit viral protein synthesis
- degrade viral RNA
- inhibit virion assembly
- increase MHC I presentation
Comes from: produced by virally infected cells
Role: alerts neighbors to induce an antiviral state and prevent infection
Compare and contrast Type 1 interferon (alpha and beta) and Type 2 interferon (gamma).
Type 1:
- alpha and beta
- protects against viral infection
Type 2:
- gamma
- activated by adaptive immune system TH1 cells
List a few important properties of a vaccine that would stimulate CTLs.
1) Protein in the cytosol (via endogenous pathway)
2) ISCOMS in micelle (fuze with cell membrane) and puts protein into cytosol
