L14: Cell Mediated Cytotoxic Responses Flashcards
the primary agents of cell-mediated (TH1)immunity are the____ cells
Tc and NK
Lymphoid cells developing in the thymus ___rearrange TCR genes
DO rearrange
Lymphoid cells developing in the bone marrow ____ rearrange TCR genes
DO NOT
Lymphoid cells that develop in the thymus:
TH
TC
γδ T cells
NKT cells
Lymphoid cells that develop in the bone marrow:
B cells
NK cells
TH cells
TH- signal to tailor and coordinate responses.
TC cells
TC– attack and kill cells displaying specific antigens by disrupting membrane andlysing cell.
γδ T cells
- patrol epithelia
- attack and kill pathogens and rogue-self using same mechanisms as NK and TC cells
- signal
- Some authors refer to these as“primitive” because their function seems less specialized.
Two types of NKT cells
- NKT
- iNKT
iNKT cells (type 1)
respond to lipid antigens,especially those characteristic of bacteria.
NKT cells (type 2)
recognize a wider array of lipids and have more variation in the receptor
____ cells perform functions native to TH, TC, NK, Treg, and γδ T cells
iNKT
B Cells
- rearrange immunoglobulin genes, phagocytize, but do not seem to be aprimary killer of pathogens, and do not attack rogue self.
- The antibodies that they produce are often important in directing attack by other cells.
NK cells
- do not rearrange any genes.
- They attack and kill cells withsuspicious surface displays by disrupting their membranes and lysing the cells.
Myeloid cells
- macrophages
- neutrophils
- eosinophils
Macrophages
macrophages – phagocytize, present antigen
neutrophils
neutrophils – phagocytize, do not present antigen
Eosinophils
eosinophils – coordinate attack on eukaryotic parasites, do not present antigen,weakly phagocytic
Steps for activating TC cells
- The TC cell binds a foreign antigen on MHC I (TC cells that bind self-antigen have been killed off during negative selection.)
- CD45R on TC and TH attaches to CD22 (sometimes called CD45L) on target cells.
- TH cell activates the cell, turning it into a CTL.
____ speeds TC activation by making it easier for the Tc cells to encounter the foreign antigen.
Cross presentation
Activation of TC cells leads to:
a. Cell division
b. Up-regulation of cell adhesion molecules
c. Synthesis of the complete IL-2 receptor
CTL cell attached to target will up-regulate ____, forming
conjugate.
cell adhesion molecules
Steps for CTL attack on target cell membrane:
- cytoskeleton rearranges, directing Golgi and storage granules (perforins and granzymes) to target cell
- granule contents released by exocytosis (Ca2+ dependent)
- Perforin monomers undergo conformational change and insert in the targetmembrane (sequence homology with C9 of the complement system).
- Granzymes (serine proteases) enter through pores and activate apoptosis.
Alternatively, CTLs can induce apoptosis by ____
Fas ligand binding to target Fas receptor on the target cells
Cells from mice that are both perforin knock-out AND Fas knock-out _____ be killed by cytotoxic T cells.
CANNOT
CTL-dissociation
- The integrin holding the cells together reverts to its less avid form after 5 to 10 minutes.
- The CTL undocks and begins looking for another cell to hit.
CTL destroyed cells are scavenged by __
macrophages or neutrophils
Characteristics of NK cells
- Large cells with lots of granular inclusions.
- Lymphoid, sharing a common progenitor and surface markers with T cells,including the use of signaling peptides similar to those in the complete CD3complex
- Develop in the bone marrow and do not rearrange genes
- Also have TLRs and inflammatory cytokine receptors typical of those ofmacrophages and neutrophils
- Do express the receptor of FC of IgG (CD 16) and the IL-2 receptor. This allowsthem to recognize and attack antibody-coated cells during ADCC
- Have MHC I receptor, but it is inhibitory, and not used to recognize antigen, butrather viral down-regulation.
NK mechanism of killing
- Granules containing perforins and granzymes directionally released at target cell
- Constitutively cytotoxic; do not require activation
- Do not require antigen or MHC recognition
- Adhesion to target triggers release
However virus that down-regulate MHC I production may fool ___, but they will activate ___ cells.
fool TC cells, activate NK cells
Stress receptors are possesed by ___ cells
NK cells
-There are a variety of stress indications displayed by sick cells,and a variety of receptors used by NK cells to sense them. The interaction promotes attack.
______ not only lowers the cell’s MHC
production, it attempts to fool the NK cells by producing a fake MHC.
Cytomegalovirus
- The viral genome codes for a proteinresembling MHC I.
- This does not activate TC cells as it does not display foreign antigen.
- However, it is recognized as MHC I by NK cells of susceptible mice.
- The fake MHC binds to the same NK inhibitory receptor that real MHC binds to.
How does Antibody Dependent Cell Mediated Cytotoxicity (ADCC) work?
- Targeting of cell harboring pathogens.
- The cells display abnormal antigen.
- B-cells produce antibodies to this antigen
- The antibodies attach so that their FC portion stick out from the cell.
Which cells are capable of ADCC?
1) Cells with Antibody (FC) Receptors
a. NK
b. macrophages
c. neutrophils
d. eosinophils
NK cells recognize ____, attacking ____, resulting in ____
IgG and IgM, rogue self, apoptosis
Macrophages recognize ____, attacking ____, resulting in ____
IgG and IgM, pathogen, phagocytosis
neutrophils recognize ____, attacking ____, resulting in ____
IgG and IgM, pathogen, phagocytosis
Eosinophils recognize ____, attacking ____, resulting in ____
IgE, parasites, surface attack
Graft vs Host disease
- Supply immuno-incompetent individual with competent lymphocytes from another genetically different individual.
- The Tc cells activate and begin to attack the host cells.
- The B cells produce antibodies to the host cells surface antigen.
- The patient experiences a cell-mediated attack from both NK and TC cells, withsome help from the macrophages, neutrophils and maybe even complement.
- The cells under heaviest attack are GI epithelial (diarrhea), skin (which mayslough off in sheets), and spleen, (which may attack the red blood cells, resultingin jaundice). The whole response can kill a person.
