1.4.1 T Cell-Mediated Immunity Flashcards
What are the three classes of receptors that can activate a naive T cell?
TCR, Co-receptor (CoR), and Cytokine Receptor (CyR)
Where do naive T cells encounter their specific antigen? Do the necessary components find each other?
The naive T cells encounter their specific antigen in the paracortex of the LN being presented by an APC (most commonly a DC); The naive T cell finds the Ag by crawling over the DCs until it finds an Ag that it has affinity for.
Describe the affinity of the interaction between TCRs and their corresponding Ag. What other factors can contribute to the infinity of the interaction b/t T cells and APCs.
Low affinity; Co-receptors, Abs, Adhesion molecules, and growth factors
What is the activating receptor of a CD4+ T cell? What does it bind to on the APC?
CD-28; B7-1 and B7-2
Which receptor blocks the activity of the CD-28 by binding its ligand?
CTLA-4
What receptor and ligand interaction contributes a large amount of affinity of the adhesion b/t a CD4+ T cell and an APC?
LFA-1 (receptor: lymphocyte function-associated antigen 1) and ICAM-1
What is the stimulatory ligand found on APCs (B cells, DCs, Macrophages)
B7-1 and B7-2
What are the components of the T-cell co-receptor LFA-1 which binds ICAM-1? Which cells express ICAM-1?
CD11a and CD18; fibroblasts, endothelial cells, macrophages, DCs
Name two inhibitory T cell receptors?
CTLA-4 (B7-1 and B7-2) and PD-1 (PD-L1)
What type of cells express CD25? What is its binding counterpart?
T cells, IL-2
Describe the initiation of TCR signaling pathway.
1) Receptor ligation
2) Phosphorylation of ITAMs (intracellular tyrosine-based activation motifs) by Lck
3) Recruitment & activation of ZAP-70
Once ZAP-70 is activated, it works on what two intracellular molecules? What are the resulting transcription factors?
PLC(gamma) and MAPK; (If you remember FOM) PLCgamma is cleaved into IP3 and DAG. IP3 leads to NF-AT and DAG leads to NF-kappaB. MAPK leads to AP-1
Where do cyclosporine/tacrolimus work to inhibit one of the signaling cascades?
Cyclosporine/tacrolimus inhibits calcineurin (that works downstream of IP3). By inhibiting calcineurin, it can no longer dephosphorylate NF-AT. The dephosphorylation of NF-AT is what allows it to enter the nucleus.
What are the cytokines induced by NF-kappaB?
IL-2, INF-gamma, and TNF-alpha
What are the cytokines induced by NF-AT?
IL-2, IL-4, INF-gamma, and TNF-alpha
What are the cytokines induced by AP-1?
IL-2
What is the biological target of Sirolimus (rapamycin)?
Rapamycin inhibits mTOR reducing protein tln
What is the mechanism of Abatacept (CTLA-4-Ig)? What is its indication?
Binds B7-1 and B7-2, which prevents CD28 from being activated; indicated for rheumatoid arthritis
What are the 3 signals required in the activation of T cells?
TCR ligation, Co-receptor ligation, and Cytokine stimulation
What are the cytokines responsible for the activating cytokine autocrine stimulation? paracrine stimulation?
autocrine: IL-2
paracrine: APC
Which ILs are in the same family that share the same gamma chain?
IL-2, IL-15, IL-7, IL-9, IL-4
What two therapies are used as IL-2 blockers?
Daclizumab (prevents organ rejection) and Tofacitinib (rheumatoid arthritis)
What kind of immune response is used to combat an extracellular bacteria? What type of helper T cell?
IgG/IgA, complement, neutrophils; Tfh/Th17
What kind of immune response is used to combat an intracellular bacteria? What type of helper T cell?
Macrophages and CD8+ T Cells; Th1
What kind of immune response is used to combat fungi? What type of helper T cell?
Neutrophils and macrophages; Th1/Th17
What kind of immune response is used to combat helminths? What type of helper T cell?
Mast cells and IgE (B cells); b/c helminth infections are not common in developed countries, IgE is the mediator of many allergic reactions; Th2
What ILs are produced by Th2?
IL-4, IL-5, and IL-13
What is expressed by Tfh?
CD40L and CXCR5
When a DC encounters a pathogen it can induce many different types of helper T cells, what are the cytokines it uses to induce the production of these cells?
Th1: IL-12, IFN gamma
Th2: IL-4
Th17: TGFbeta and IL-6
What makes the activation of memory T cells different from effector T cells?
Become activated with low levels of antigen without co-stimulation (hair trigger)
