Cytoxic T cells & NK Cells (1/10) Flashcards
What are the similarities and differences between NK cells and killer T cells?
What happens if you have too many cytoxic T cells? Too few?
Too many/too active: autoimmune, hypersensitivity reactions, graft v host disease, transplant rejection
Too few: immunodeficiency syndromes with decreased NK function
What makes cytoxic T cells so dangerous?
Cytotoxicity: granzyme/perforin pathway, death receptor pathway (Fas/Fas ligand, TNF-related apoptosis-inducing ligand)
Immune modulation: production of inflammatory cytokines (IFN-gamma, TNF), chemokine secretion, immunomodulatory cytokines (IL-10, GM-CSF)
How does the T cell kill?
Activates an endogenous apoptosis program in the target cell
LFA1 (on T cell) and ICAM1 (on target) recognize one another and make a tight seal
TCR and MHC-1 bind and tell the cell if it’s a good match
Porphorin makes a pore → granzymes diffuse into the target and activate the caspase cascade & apoptosis program as a result
FasL on T cell binds Fas on target cell which also activates caspase cascade and apoptosis
How do you get rid of the T cells once there is no more virus?
Activated T cell expresses Fas & it can undergo apoptosis
This terminates the immune response
It’s interesting because Fas is same pathway that induces apoptosis on target cells
Note that tumor cells are particularly susceptible the this method of killing
TRAIL (?)
- How are T cells activated? Which signals are required?
Dendridic cells present antigen in lymph node/spleen to naïve T cells that have never seen an antigen. Then they decide if it’s the right fit
2 signals are required (safety measure)
• MHC class I/TCR
• CD80/86 on dendridic cell and CD28 on T cell
- What else can dendridic cells activate?
CD4 positive (helper T cells) which help the CD8/killer T cells and the B cells
- How do DC get the liscence to activate CD8? 2 steps
DC cell shows piece of virus to T cell → activates a CD4+ helper cell which has a lower threshold for activation
CD4 with CD40L activates the CD40 R of the dendridic cell, making the DC more potent
Now the DC is more potent and can turn on the CD8 positive T cell
- If there is no liscencing, what happens?
There is no costimulatory signal
How do viruses hide from cytoxic CD8 T cells?
Latency: having fewer copies of virus around so fewer are detected i.e. herpes, HIV
Antigenic variation: rapid mutation/tumor markers
Infection of immune privileged sites i.e. the brain
Production of homologs of Bcl-2, the anti-apoptotic molecule
Interfere with the processing/presentation of the MHC I on their surface
What is the difference between direct presentation and indirect presentation?
MHC I present peptides from pathogen that have been processed in the ER, loaded, and presented on cell surface
Cross presentation happens only in a specific type of DC
Pieces of dead pathogen are floating extracellularly & would normally be presented on MHC II via endocytosis/MHC II loading
But Class II can only be seen by CD4 helper T cells, which don’t have cytotoxic potential
Instead of getting loaded on to class II, it releases its antigens into the cytoplasm so it can go to the proteasome & get loaded onto MHC I
- What if a virus directly infects and shuts down the antigen presenting cell?
(usually suts down MHC I presentation pathway, though not all at once)
Cross-presentation pathways can take over
Why don’t DC undergo apoptosis when they present viral particles on their surface?
They don’t have the machinery downstream to undergo apoptosis (even though they express Fas on their surface)
- What are NK cells? What receptors do they have?
o Killer cells of innate immunity
o Germline encoded receptors that have many alleleic variants:
o CD56 = adhesion molecule
o CD16 = receptor for Fc gamma (part of IgG) which binds IgG and stimulates antibody dependent cytotoxicity
o KIR = recognizes MHC class I molecules
Where can NK cells be found?
Peripheral blood
Secondary lymphoid organs: bone marrow, spleen, activated lymph nodes
Peripheral tissue: liver, lung, and decidual lining of uterus
- How do NK cells recognize and kill tumors?
3 pathways:
Granule exocytosis pathway
Death receptor pathway
IFN-gamma, nitric oxide
