HRR: T cell activation and differentiation Flashcards
__ cells are more likely to be in lymphoid organs, while ___ are out and about
B; T
Cell mediated immunity involves __ cells, and humoral immunity involves __ cells
T; B
Which cells in cell-mediated immunity kill tumor cells?
CD8+ T cells
Which cells help B cells produce antibodies?
CD4+ T cells
List the phases of T-cell responses and where each occurs in the body.
1.Recognize antigens in peripheral lymphoid organs
2.Proliferate and differentiate into effector cells while in the lymph node
3.Traffic to peripheral tissues via blood/blood vessels
4.Perform function when activated by their antigen in a given tissue
What is IL-2?
Activated T cells start secreting IL-2, which is a growth factor. This aids in their proliferation.
Compare IL-2 and IL-7
IL-2 is involved in proliferation and differentiation of mature naïve T cells, while IL-7 is involved in proliferation of pre and immature T/B cells
Identify the source of IL-2, the primary growth factor for T-cells, and explain why antigen-activated T-cells proliferate more in response to it than naïve T cells.
1.T cells are activated by antigen and co-stimulators, and produce IL-2
2.IL-2 secretions leads to the expression of IL-2Ra chains, also known as CD25, in activated T cells that have high affinity for the IL-2RaBy complex.
3.This expression allows T cells to be greedy and soak up as much IL-2 as possible. This is what allows activated T cells to take up more IL-2 than naïve ones!
What are the main key identifying markers for T cells?
CD3 (all T cells) and either CD4 or CD8
What is the function of costimulatory molecules?
They’re the second “danger” signal displayed by APC; they help prevent T cell activation by harmless foreign substances
What are the most important APC costimulatory molecules? What do they bind to on the T cell?
B7-1 (CD80) and B7-2 (CD86); they bind to CD28 for activation and CTLA-4 for inhibition
- What are the main costimulatory molecules found on T cells
CD28, CTLA-4, PD-1
describe CD28
It is always expressed and will interact with B7 1 or 2 on antigen presenting cells.
Describe CTLA-4
a costimulatory molecule ont eh surface of T cells that blocks/removes B7 1 or 2 on antigen presenting cells; it prevents signal transduction and proliferation. it acts mostly on maturing T cells and is used in Tregs. It acts evenly on CD4 and CD8.
Describe PD-1
It interacts with PD-L1 or 2 on antigen presenting cells, tissue cells, or tumor cells. It is on the surface of T lymphocytes and inhibits signals from TCR and CD28 by activating a phosphatase to remove phosphate from the zeta chain.
which inhibitory molecule on T cells acts on those in the effector phase?
PD-1
which inhibitory molecule in T cells acts on those that are maturing?
CTLA-4
which inhibitory molecule has a preference for CD8 over CD4?
PD-1
Describe LFA-1 and ICAM-1
They’re adhesion molecules. LFA-1 is on the T cell and ICAm-1 is on the APC
Describe the T-cell receptor and MHC requirements for signal transductions
You need multiple MHC-TCR complexes close together interacting for several minutes! The T-cell receptor will also need its CD4/8, CD3, and zeta costimulatory molecules
What is the co-stimulatory molecule specific for helper-T cells?
ICOS; it is an activation signal!
In what scenario do CD8+ T cells require stimulation from helper T cells?
When the APC ingest whole cells (phagocytotic) to present antigen; this usually means both MHC I and II are present, and CD4+ and CD8+ T cells will bind antigen and costimulatory molecules right next to each other. This is a good example of cross presentation
Explain the role and configuration of adhesion molecules in an immunological synapse.
Adhesion molecules stabilize the clustering of MHC-TCR complexes in order to lead to signal transduction. The most common one is integrin LFA-1 that binds to ICAM-1. It normally has low affinity, but the affinity increases in the presence of chemokines from the innate immune response. They form an immunological synapse by surrounding the TCR-MHC complexes.
what is polyclonal activation
Polyclonal activation is antigen independent activation of T cells, and just requires holding a bunch of MHC-TCR complexes together. These can cause release of large and dangerous amounts of cytokines. This is not normal and is pathogenic.
describe lectins in terms of polyclonal activation
bind to carbohydrate side groups on TCR or CD3. Cross-linking of several at once generates the activation of a signal in the absence of antigen
describe superantigens in terms of polyclonal activation
cross-linking MHC on antigen presenting cells with TCR complexes in the absence of a specific antigen. They can only activate certain T cells, but it is still enough to cause disease. This one is a naturally-occurring example seen in TSS!
Describe the biochemical pathways that connect antigen recognition by the TCR complex and transcription of NFAT
1.LCK is activated by the clustering of MHC-TCR complexes and associates with CD4 or CD8. Once activated, LCK phosphorylates ITAMS on the zeta costimulatory molecule.
2.ZAP 70 (a zeta-associated protein), binds to the phosphorylated regions. This attracts several other signaling molecules, including PLC-y1.
3.PLC-y1 increases DAG and cytosolic Ca 2+.
4.Ca 2+ activates the enzyme calcineurin, which activates the transcription factor NFAT
Describe the biochemical pathways that connect antigen recognition by the TCR complex and transcription of NF-kb
1.LCK is activated by the clustering of and associates with CD4 or CD8. Once activated, LCK phosphorylates ITAMS on the zeta costimulatory molecule.
2.ZAP 70 (a zeta-associated protein), binds to the phosphorylated regions. This attracts several other signaling molecules, including PLC-y1.
3.PLC-y1 increases DAG and cytosolic Ca 2+.
4.DAG activates the enzyme PKC, which activates the transcription factor NF-kb
Describe the biochemical pathways that connect antigen recognition by the TCR complex and transcription of AP-1
1.LCK is activated by the clustering of and associates with CD4 or CD8. Once activated, LCK phosphorylates ITAMS on the zeta costimulatory molecule.
2.ZAP 70 (a zeta-associated protein), binds to the phosphorylated regions. This attracts several other signaling molecules, including a GTP/GDP exchange factor
3.GTP/GDP exchange on RAS increases RAS-GTP
4.RAS-GTP activates the enzymes ERK and JNK, which activates the transcription factor AP-1. This triggers DNA replication and proliferation
Describe the biochemical pathways that connect antigen recognition by the TCR complex and protein synthesis
1.LCK is activated by the clustering of and associates with CD4 or CD8. Once activated, LCK phosphorylates ITAMS on the zeta costimulatory molecule.
2.ZAP 70 (a zeta-associated protein), binds to the phosphorylated regions. This attracts several other signaling molecules, including a PI3-kinase
3.PI3 kinase activates PIP3
4.PIP3 activates enzymes AKT and mTOR, which activate protein synthesis!
What is rapamycin?
An immunosuppressant drug that targets AKT/mTOR
What is cyclosporin A?
An immunosuppressant drug often taken in people receiving organ transplants that targets calcineurin. This will block NFAT transcription factor.
What are cytokines?
Molecules that are produced in response to antigens that act in autocrine or paracrine fashions. They can have many biological effects (pleiotropism) and are redundant (many cytokines have similar effects).
Do CD4 or CD8 cells expand more?
CD8! They expand 100,000 fold in a few days, where CD4 expand 100-1000
What are the 4 CD4+ T cells? Which one stays on the lymphoid organ?
Th1, Th2, Th17. Tfh; Tfh stays in the lymphoid organ!
what 3 cell surface molecules mediate naive T cell movement
L-selectin, LFA-1, CCR7
what 3 cell surface molecules mediate effector T cell movement
E and P selectin, LFA-1 and VLA-4, and CXCR3
what is the function of L-selectin in naive T cells
it adheres naive T cells to HEV in the lymph node
what is the function of LFA-1 in naive T cells
stabilizes the naive T cell on HEV
what is the function of CCR7 in naive T cells
activates integrins and chemotaxis that takes them to the T cell-area of lymph nodes
what is the function of E and P selectin in effector T cells
weak adhesion of effector and memory T cells to cytokine activated endothelium at site of infection
what is the function of LFA-1 and VLA-4 in effector T cells
stablilizes the activated T cell on the activated endothelium
what is the function of CXCR3 in effector T cells
activates integrins and chemotaxis and causes the T cell to go through the vessel and into the tissue
