Lecture 8 - Effector T Cell Response Flashcards
What changes are seen in naive T cell priming
1 - forms a stable synapse
2 - increase T cell adhesiveness to APCs
3 - induction of pro-survival signal
4 - increase in metabolic activity
5 - increased transcription
why is it necessary to increase the metabolic activity of T cells
for cell proliferation and production of effector molecules, receptors, integrins, etc.
How is TCR signaling initiated
tyrosine phosphorylation within the cytoplasmic region of immunoreceptors (ITAMs)
summarize:
PLC-y-mediated T-cell activation
- intracellular calcium entry
- activation of RAS
- activation of protein kinase
summarize:
T cell changes after TCR signaling
- increased cell survival
- increased metabolic activity
- increased gene transcription
- increased growth factor production
The T cell receptor has many functional components, some of which are involved in signal transduction, while others are involved in antigen recognition. What two elements are involved in antigen recognition?
TCRa and TCRb
Why are lymph nodes palpable after infection
rapid stromal expansion of immune response
What antigen receptors give rise to CD4 an CD8 T cells
alpha and beta
T/F: cytokines in APCs dictate what T cell differentiate to
True
what are the master regulator transcription factors of CD4+ T cells
T-bet
GATA-4
RORyT
BcI-6
FoxP3
T/F: T helper cells regulate
False - activate
What T helper cell targets extracellular bacteria
TH17
what immune cells do TH17 target for enhanced response
neutrophils
What major cytokines and their actions in TH17
IL17 and IL22
recruit neutrophils
increase cell turnover
direct killing of bacterium on epithelium
What T helper cell targets intracellular bacteria
TH1
what immune cells do the TH1 target for enhanced response
macrophage
What major cytokines and their actions have in TH1
IFN-y
recruit macrophages and increase phagocytotic capability
kills chronically infected cells
What immune cell targets helminth infections
TH2
what immune cells do the TH2 target for enhanced response
eosinophils, mast cells, basophils
What major cytokines and their actions have in TH2
IL4/5
increased cell turnover and mucus
increase smooth muscle contraction
T/F: antibodies are effective no matter where they are found
False - only effective while a pathogen is outside the cell
How are cytotoxic T cells like serial killers
recognizes “targets” (viral-infected cell), will bind and initiate apoptosis on specific cell
extrinsic removal
activation of death receptors via ligands
intrinsic or mitochondrial removal
response to noxious stimuli
what specialized protease is common to both extrinsic/intrinsic pathways
aspartic acid-specific cysteine proteases (CASPASES)
Initiator caspases
promote apoptosis by cleaving and activating others
Effector caspases
initiate intracellular breakdown for apoptosis
Perforin
delivers contents of granules into the target cell cytoplasm
Granzymes
activate apoptosis in the cytoplasm of the target cell
Granulysin
antimicrobial actions
summarize what happens once a cytotoxic T-cell
1 - perforin creates pores
2 - granzymes enter the cell and trigger mitochondria
3 - cytochrome C released
4 - caspase activation
5 - intracellular changes
6 - apoptosis
What are the 4 steps in T cell killing of target cells
1 - recognition
2 - proliferation
3 - differentiation
4 - effector (killing)
Define what co-inhibitory receptors do
regulate un-controlled activation of lymphocytes through competition with CD28
What are the immune checkpoints
co-inhibitory molecules expressed by T cells CD152 and PD1
ITIM
immunoreceptor tyrosine-based inhibitory motif
ITIM inhibits TCR signaling through
dephosphorylation
How do Tregs regulate T effector cells
directly or via APCs
how does infection response progress in the body
- establishment of infection
- inductive phase
- effector phase
- memory phase
What does the asymmetric division of a T cell produce
Helper and Memory T cell precursors
how do corticosteroids work
block NF-kB responses (T cell proliferation, apoptosis of developing thymocytes, etc)
how does tacrolimus work
blocks IL, IFN-y
How does cyclosporine work
selective immunosuppressant blocks TH1 responses
What 3 signals do APCs deliver to T cells
- TCR activation
- Survival
- Differentiation
Naive CD4+ cells differentiate to
TH1, TH2, TH17, THf, THreg
TH1 secretes _____ and provides immunity against ______ bacteria
IFN-y and IL-2; intracellular
TH2 secretes ______ and provides immunity against ______ bacteria
IL 4/5/13; helminths
TH17 secretes ______ and provides immunity against ______ bacteria
IL17/22; extracellular
THf secretes _____ and
IL21; help b cells isotope switching
