T Cell I Flashcards
What type of antigens do MHC I present and what T cell type do they present to?
Intracellular antigens and present to CD8 CTLs
What type of antigens do MHC II present and what T cell type do they present to?
Extracellular antigens and present to CD4 T helper cells
Which events in the T cell life cycle occur in primary lymphoid organs?
Ag recognition via APC presentation, induction and T cell expansion and differentiation
What are the effector functions of CD4 cells?
Leukocyte activation (inflammation), phagocytosis and killing of microbes
What are the three types of stimuli critical for T cell activation?
Antigen recognition, costimulation to maximize, and cytokines (IL-2) to amplify/ direct response
Which steps in the T cell lifecycle are common between CD4 and CD8 T cells?
Ag recognition, activation, clonal expansion, differentiation
What is the function of CD3?
Signal transduction via ITAMs
What is the function of CD28 and what does it bind on the APC?
Signal transduction (costimulation) via B7-1 or B7-2
What is the function of CTLA-1 and what does it bind on the APC?
Negative regulation and binds B7
What is the function of LFA-1 on T cells and what does it bind?
Adhesion, signal transduction. binds ICAM-1 on APCs and endothelium. Helps change binding to high affinity after antigen binding
What is the function of VLA-4 and what does it bind?
Adhesion, signal transduction. Binds VCAM-1 on endothelium
Does the TCR have a signaling domain?
NO. just used to bind MHC/ antigen and coreceptors. Their high diversity variable chains paired with consistent signaling domains
What are the steps to signal transduction in the T cell (TCR to ZAP-70)
- alpha/ beta chains bind peptide +MHC
- CD3 complexes with ITAMS
- CD4/8 tails associated with Lck src kinase
- CD45 phosphatase removes inhibitory phosphate on Lck
- Lck phosphorylates ITAMS on CD3
- phosphorylated ITAMS= Zap-70 binding site
- Zap-70 phosphorylated by Lck= docking site
What kind of protein is Lck, how is it activated, and what is its function?
Src kinase activated by CD45. Phosphorylates ITAMS on CD3 and Zap-70
What two signals are required for TCR signal transduction?
TCR/ MHC/ coreceptor + CD28 signal (and IL-12 release)
What 3 proteins are a product of the TCR signaling pathways and what pathways are they associated with?
- NFAT (PLC/Calcineurin dephosphorylation)
- NFkB (IkB inhibitory phosphorylation)
- AP-1 (Fos/Jun joining)
What is the function of NFkB in the TCR signaling pathway?
IL-12 transcription (activation of NK cells)
What is the first genetic change in T cell metamorphosis?
IL-2 and IL-2R gene txn = signal for T cell differentiation/ activation/ clonal expansion
Which molecule is the earliest detected surface marker in activated T cells?
CD69
What does T cell activation and transcription of Il-2 entail?
Causes binding of the alpha chain to switch from low affinity to high affinity= launch of clonal expansion
What three chains make up the IL2-R?
alpha, beta, gamma
What signaling pathway is associated with the gamma chain of the IL-2R?
JAK3 signaling. Mutation= SCID
What is the function of Rampamycin?
Inhibits IL-2 signaling
Name four properties of T cell cytokines
- produced transiently
- Usually acts in autocrine or paracrine fashion
- Pleiotrophic
- Redundancy
Which cells produce IL-2?
CD4/ CD8
Which cells produce IL-4 and what is its function?
CD4/ mast cells. Function = B cell switching to IgE
Which cells produce IL-5 and what is its function?
CD4/ mast cells. Eosinophil activation
Which cells produce IFN-gamma and what is its function?
CD4/ CD8/ Natural killer cells. Function= macrophage activation
Which cells produce IL-17 and what is its function?
CD4 + others. Function= Stimulate acute inflammation
Which cells produce TGF-Beta and what is its function?
CD4 + others. Inhibit T-cell activation and cause differentiation of Treg cells.
