MI 03b: T Cell Activation Flashcards
Goals of T cell activation: to generate (X) and (Y).
X = large number of effector cells Y = antigen-specific memory T cells
What defines a “naive” T cell?
Hasn’t encountered antigen yet (recirculating)
Epithelial barrier is breached. Microbes and their products are taken up by (X), which process the protein components into (Y) for MHC presentation.
X = dendritic cells Y = peptides
As DCs process antigen, they migrate from (X) to (Y).
X = infected tissue Y = T cell zones (draining lymph nodes)
T/F: During migration to T cell zone, DCs upregulate expression of MHC and co-stimulatory molecules.
True
T/F: Upon activation, T cell leaves the lymph node right away.
False - stays in lymph node for few days
T cell activated. Which subsequent processes occur prior to it leaving lymph node?
- Receptors and signaling pathways activated
- Surface molecules change
- Cytokines produced
- Clonal expansion
The cytokine (X) is particularly important in T cell proliferation.
X = IL-2
T cell activation: Signals from different (X) enable differentiation of CD4 T cells to (Y) or CD8 T cellsto (Z).
X = cytokines; Y = helper T cells Y = cytotoxic T cells
In normal, healthy T cell response, expansion and decline of responses occurs over (X) period of time.
X = 1-2 weeks
Blood-borne pathogens are captured by (X) cells, primarily in (Y) location.
X = APCs Y = spleen
T/F: DCs are the best APCs.
True
What are the classes of DCs?
- Classical
2. Plasmacytoid
(X) class of DCs is the primary source of (Y), which are crucial for anti-viral immune response.
X = plasmacytoid Y = Type I IFN
Which class of DCs primarily responsible for presenting antigen to naive T cells?
Classical
Unstimulated DCs typically reside in:
Epithelial and sub-epithelial tissue layers
What do bored, unstimulated DCs typically do in their spare time?
Very mobile and phagocytic (constantly sample environment for microbes)
T/F: DCs themselves may be infected by viruses.
True
It’s typically (X) binding to (Y) of DCs that begin their maturation process.
X = PAMPs Y = PRRs (i.e. TLRs)
As DCs take the trip to T cell zones, which of their molecules are (up/down)-regulated?
Up-regulate:
- MHC
- B7 co-stim
- ICAM-1 (integrin ligand)
- CCR7 (chemokine receptor)
Which integrin (receptor/ligand) is up-regulated on migrating DCs?
Ligand;
ICAM-1
Maturing DCs know the path to T cell zone because they (gain/lose) (X) and (gain/lose) (Y).
Lose;
X = adhesiveness to epithelial cells
Gain;
Y = expression of CCR7 chemokine receptor
Migrating DCs express (X) receptor, which directs them toward (Y) via chemotaxis. The chemokines are produced by (Z).
X = CCR7 Y = Z = lymph nodes
(One/hundreds) of naive T cells will interact with (one/hundreds) of DCs in any given day.
One; hundreds
Which signals are necessary for T cell activation?
- Antigen recognition
2. Co-stimulation
T/F: TCR is a signaling molecule.
False
T/F: TCR is non-covalently associated with signaling molecules.
True
TCR of naive T cell binds complementary peptide-MHC complex. Signal transduction occurs via which molecule(s)?
CD3 and zeta chains
T/F: Signal 2 of T cell activation involves CD4/CD8 co-receptors.
False - they’re involved in signal 1
(X) co-receptors on T cells increase binding (affinity/avidity) between TCR and APC. This is involved in Signal (1/2) of T activation.
X = CD4 or CD8
Avidity;
Signal 1
Signal 2 of T activation provided by binding of (X) to (Y).
X = CD28 on T cell Y = B7 on DC
There’s (positive/negative) feedback in Signal (1/2) of T activation. Describe this.
Positive;
Signal 2;
T cells further up-regulate CD28 expression upon receiving co-stimulatory signal from DCs
In general, T activation signals 1 and 2 work together. Signal 1 provides (X). Signal 2 provides (Y).
X = specificity Y = protection against autoimmunity
T cell activation: T cell contains integrin (receptor/ligand) (X) that binds to (Y) on APC.
Integrin receptor
X = LFA-1;
Y = integrin ligand (ICAM-1)
It’s important to avoid (over/under)-production of (X) cytokine, a potent T-cell growth factor. How is this done?
Over-production;
X = IL-2;
Its mRNA is inherently unstable
Signaling from T cell activation causes which events to occur, in terms of IL-2 production?
Increased IL-2 production via:
- Stabilization of mRNA
- Up-regulate transcription factors
Activated T cells have (more/less) (receptors/affinity) for IL-2.
More receptors and increased affinity
IL-2 in T cell activation has (autocrine/endocrine/paracrine) actions.
Autocrine (same cell) and paracrine (nearby T cell)
Which region(s) of which cell(s) constitute the immunological synapse?
Contact region between T cell and APC
Within immunological synapse (on T cell), (X) receptors/molecules cluster and (Y) are pushed to periphery.
X = TCR, co-receptors, and CD28 Y = LFA-1
Lck is a(n) (X) that’s associated with (Y) in/on (surface/cytosol) of (Z) cell.
X = tyrosine kinase;
Y = CD4 or CD8 co-receptors
Cytosol;
Z = T cell
Lck action.
Phosophorylation of ITAMs on CD3 and zeta chains
ITAMs are (X)-based activation motifs found on (Y) in (Z) cell.
X = Tyrosine; Y = CD3 and zeta chains Z = T cell
(Dephosphorylated/phosphorylated) ITAMs stimulate signaling along which pathways?
Phosphorylated;
- PLC(gamma)
- Ras/Rac
- PI3 kinase
T cell signaling pathways final generated products.
Transcription factors (NFAT, NFkB, AP-1)
T cell signaling pathways are important targets for (X) drugs.
X = immunosuppressive
(X) cells are unique in having the capacity to bypass rules of antigen presentation via cross-presentation. Explain.
X = dendritic
Microbe phagocytosed (MHC II loading) and, during processing, some antigen spills into cytosol (now also available for MHC I loading)
There’s a safeguard in place for differentiation of CD(4/8) T cells into cytotoxic T cells. What’s the safeguard?
CD8;
CD4 T cells must be co-activated (produce cytokines that aid differentiation)
Some pathogens secrete (X), which induce unspecific activation of many CD(4/8) T cells and massive release of (Y).
X = super-antigens;
CD4;
Y = cytokines
List the subsets of T helper cells that CD(4/8) T cells can differentiate into.
CD4;
Th1, Th2, Th17, Tfh
Difference between Th1, Th2, and Th17 cells is essentially which (X) they (Y).
X = type of pathogen Y = are programmed to fight
Tfh, aka (X), cell has key role of:
X = follicular helper T cell
assisting B cells with Ab production
T/F: The T helper (effector) cells don’t exit peripheral lymphoid organs.
False - only Tfh doesn’t exit
List the general types of receptors expressed on T cells that allow for their migration/trafficking.
- Chemoattractant receptors
- Selectins
- Integrins
Naive T cells express which receptor(s) to direct their trafficking to (X)?
- CCR7
- L-selectin
- LFA-1 (integrin)
X = T cell zone
Naive T cells migrate from (X) into (Y) through (Z) structures.
X = blood circulation Y = lymph node T cell zone Z = high endothelial venules (HEVs)
(X) are specialized endothelial cells that facilitate (slowing/speeding) of T cells through which interactions?
X = HEVs;
Slowing;
- L-selectins
- Integrins (ICAM-1 and LFA-1)
L-selectin (ligand/receptor) on naive T cell interacts with (X) (ligand/receptor) on (Y) during migration.
Receptor;
X = L-selectin
Ligand;
Y = HEVs
Integrin (ligand/receptor) (X) on naive T cell interacts with integrin (ligand/receptor) (Y) on (Z) during migration.
Receptor; X = LFA-1; Ligand; Y = ICAM-1; HEV
Activated effector T cells, unlike naive T cells, are not drawn into (X) due to lack of expression of (Y) (receptor/ligand).
X = peripheral lymph organs;
Receptors
Y = CCR7 and L-selectin
To exit lymph nodes, (activated/unactivated) T cells up-regulate expression of (X). This will help them leave because (Y) is (higher/lower/absent) in blood.
Unactivated (circulating);
X = Sphingosine-1-P (S1P) receptor;
Y = S1P;
Higher
If T cell activated in lymph node, its exit is (facilitated/supressed) by (activation/suppression) of (X).
Supressed;
Supression
X = S1P receptor levels
