activation of T lymphocytes Flashcards
naive T cells transiently ___ with many DCs and stop when they find ___ Ag for their TCR
interact
specific
The T cells are activated to differeneitate into effector cells. Then activated T cells may:
- remain in the lymphoid organs to help:
- migrate to sites of infection to help:
- B lymphocytes
- activate macrophages
phases of T cell responses:
- Ag recognition by T cells induces ___ secretion resulting in clonal expansion as a result of cell proliferation and differentiation of the T cells into effector or memory cells
- the effector CD4 T cells response to Ags by producing cytokines that have several actions, such as the recruitment and activation of leukocytes and ____ of B cells
- the effecotor CD8 CTLs function by ____ infected and altered host cells
- IL-2
- activation
- killing
generally, T cells only recognize ____ ____ ____ Ag presented via ____
linear protein peptide
MHC
naive T cells are only activated by _____
effector T cells can respond to Ag presented by ____ and ____
DCs
B cells and macrophages
the proliferation of T lymphocytes and their differentation into effector and memory cells requires 3 signals
1.
2.
3.
- Ag recognition
- costimulation
- cytokines
superantigens:
- activates ____ T cells without the presence of Ag or other stimulatory factors
- bind MCH II on APC variable ___ subunit of the TCR; NOT the ___ ___ ___
- casuses massive proliferation and production of ____ cytokines
- CD4
- beta subunit of the TCR; NOT the peptide binding groove
- proinflammatory
mitogen
peptide or small protein that induces a cell to being cell division: mitosis
e.x. - superantigen
proliferation and differentation of T cells - Signal 1 (Ag recognition):
- TCR recognizing and binds to MHC complex on ____
- CD4/CD8 complex containing ____ phosphorylate ____ on ____ chains
- ____ binds to p-ITAMs and LCK activates ZAP-70 via phosphorylation
- ZAP-70 phosphorylates ____ and ____ which act as scaffolding for proteins
- actives the MAPK, RAS, and PLC-gamma pathway
(not a strong enough stimulation)
- DCs
- LCK ITAMs zeta
- ZAP-70
- LAT and SLP-76
proliferation and differenation of T cells - Signal 2 - Costimulation:
- ____ on naive cells wil bind to the ____ on the DC
- activation of the pathways that lead to ____ , ____ , cyclins, and differentiation factors
- upregulation of ____ and other CD28-like receptors (these are inhibitory receptors that will compete for binding with the CD80/86) to regulate the immune response
(unactivated DCs express low levels of these costimulatory molecules, while activated DCs express high levels)
- CD28 CD80/86 (B7)
- survival factors (Bcl-2) , proliferation factors (IL-2)
- CTLA-4
microbes and cytokines produced during innate immune responses (inflammation) activate DCs to express ____ , such as CD80/86 molecules
costimulators
activated DCs produce cytokines such as ____ which stimulate the ____ of naive T cells into effector cells
IL-12
differentiation
TCR-signaling alone produces a strong activation of ____ but only weak activation of ____ and ____
NFAT
NF-kB and AP-1
costimulation induces ____ and ____
NFkB and AP-1
the expression of ____ co stimulators is regulated and ensures that T lymphocyte responses are initiated only when needed
B7 (CD80/86)
CTLA-4 will bind to ____ on activated cells to prevent the further overativation of T cells
CD80/86 (B7)
CTLA-4 is not expressed on the surface of
naive and memory cells
(is stored in intracellular vesicles
major function of PD-1 is
the programmed cell death of T cells following inflammaotry immune responses
the stronger the stimulation through the TCR (and CD28) the ____ the amount of CTLA-4 that is dposited on the T cell surface
greater
PD-1 downregulates the activity of T cells and thus limits ____ ____ damage in response to a microorganism infection in that tissue
collateral tissue
PD-1 is upregulated by
IFN-gamma
excessive induction of PD-1 on T cells can induce an ____ state in T cells
anergic
proliferation and differentation of T cells - Signal 3 (cytokines-differentiation):
cytokines in the environment will determine what effector T cell is produced
- IL-12 → ____ → ____ → ____
- IL-4 → ____ → ____ → ____
- IL-6 → ____ → ____ → ____
- TFG-beta → ____ → ____ → ____
- IL-12 → STAT4 → T-bet → Th1 cell
- IL-4 → STAT6 → GATA3 → Th2
- IL-6 → STAT3 → RORgammat → Th17
- TFG-beta → SMAD2-SMAD4 → FOXP3 → Treg
changes in protein expression:
- recognition of the ____ to its antigen
- upreguation of the ____ transcription product
- ____ production and release
- ____ expression (reduces surface expression of S1PR1)
- ____ expression
- ____ expression
- cell division (growth and ____)
- TCR
- c-Fos
- IL-2
- CD69 (retention in lymph nodes)
- IL-2Ralpha (proliferation)(increases affinity of IL-2 receptors)
- CD40L (activation of DCs, macrophages, T/B cells)
- proliferation
IL-2 stimulates the ____ , ____ , ____ of Ag-activated T cells
survival, proliferation, and differentiation
characteristics of IL-2:
- IL-2 induces the anti-apoptotic protein ____
- stimulates cell cycle progression by degrdation of the cell cyle inhibitor ____
- is required for the survival and function of ____ cells
- Bcl-2
- p27
- Treg
decline and resolution of the T cell response:
- elimination of Ag leads to ____ of the T cell response
- this leads to decrease in ____ produced
- lack of IL-2 leads to decrease in ____ which leads to intrinsic apoptosis
- inhibitory receptors ____ and ____ lead to cell death
- ____ cells can regulate the survival of the remaining T cells
- contraction
- IL-2
- Bcl-2
- CTLA-4 and PD-1
- Treg
linear model of T cell differentiation
T cells differentiate → most effector cells die → a few survive and become memory cells
(most accepted)
branched theory of memory T cell differentiation
effector and memory cells are alternative fates of activated T cells (T cells differentiate into either memory cells or effector cells)
____ TF promotes the generation of memory cells
Blimp-1
memory T cells constitute the most ____ lymphocyte population in the body during the lifetime
abundant
the vast majority of memory T cells reside in ____ site
tissue (including lymphoid tissue, intestine, lungs, and skin)
the ____ TF drives differentation of effector cells in CD4 T cells
T-bet
resident memory T cells (TRM)
- produce ____ and ____
- are specific for pathogens and other Ags that have been encountered previously through that ____ epithelium
- remain at ____ sites
- IFN-gamma and TNF
- barrier
- tissue
central memory T cells (TCM):
- express ____ and ____
- home mainly to ____ , ____ and circulate in the blood
- CCR7 and L-selectin
- LNs, spleen
effector memory T cells (TEM) :
- do not ____ but produce IFN-gamma and TNF or become ____
- upon entering the tissue can become ____ cells and reside in epithelial barrier tissues at the interface between the host and the environment
- circulate in ____
- proliferate cytotoxic
- TRM
- blood
properties of memory cells:
- can survive in a quiescent state without ____
- respond to repeated exposure ____ and with a great response (naive T cells: 5-7 days ; memory T cells: 1-3 days)
- the number of memory T cells specific for any Ag is ____ than the number of niave T cells specific for the same Ag
- undergo slow ____ process leading to longer life span
- maintenance requires ____ but not antigens
- environmental ____ and ____ cytokines induce the expression of anti-apoptotic proteins and stimulate low-level proliferation
- Ag
- faster
- greater
- self-renewing
- cytokines
- IL-7 and IL-15
markers of memory T cells
IL-7R, CD45, and CD27
functional naive T cell output decreases after puberty due to thymic ____ , resulting in increased homeostatic proliferation of existing naive T cells and eventually phenotypic conversion of naive T cells into virtual memory cells
involution
in contrast to the shrinking naive compartment and its impaired ability to activate and differenetiate with age, the proportion of memory T cells increases during early life, remains stable throughout adulthood, but starts to show senescent changes after about ____ years
65
one of the most prominent T cell changes to occur with age is the loss of ____ expression and the progressive accumulation of hightly differentiated CD28- TEM cells, mainly in the CD8 T cell population
CD28
