T-Cell Immunity Flashcards
What is the site of naive T cell activation?
Secondary Lymphoid tissue
What are the phenotypic markers used to define naive T cells?
CCR7 and L-selectin
To what chemokines does CCR7 bind? What are the sources?
CCR7 binds to CCL19 and CCL21 bound on HEV and produced by activated dendritic and stroma cells of the lymphoid tissue
What are the ligands for L-selectin and where are they located?
HEV addressins CD34 or Glycam-1
In addition to the bindings of CCR7 and L-selectin, what is required for T cells to move into tissues?
LFA-1 (expressed by all T cells) is activated by endothelial chemokines and binds to ICAMs 1 and 2 to allow for diapedesis
How do interactions between T cells and APCs change upon recognition of cognate antigen?
T cell is initially bound to the dendritic cell via a low-affinity LFA1: ICAM-1 interaction; Subsequent binding of TCRs signals LFA1 to undergo conformational change that increases the affinity of the interaction and prolong the cell: cell interaction
What mediates the secondary signal needed for activation of naive T cells?
Professional APCs express co-stimulators B7.1 and B7.2 expressed after activation which binds to CD28 on the T cell.
What consequence of CD28 binding to B7 helps to dampen the reponse?
Interaction between B7 and CD28 signals T-cell expression of CTLA-4 which binds more strongly to CD28 and inhibits the interaction with B7
What are the professional antigen presenting cells found in secondary lymphnode tissue?
Dendritic cells, macrophages, and B cells
What is the most efficient antigen presenting cell?
Dendritic cell
What is an immunological synapse?
The region of contact between and T cell and APC
How is intracellular signaling of T cell activation initiated?
ITAMs on the cytoplasmic tails of CD3 and zeta chain are phosphorylated by LcK. Also bound to the ITAMs and phosphorylated by LcK is tyrosine ZAP-40 which further propagates the signal
What is the end point of signaling through ZAP-40?
Activation of 3 transcription factors: NFAT, AP-1, and NFkB
What is the first major product synthesized by T cell upon activation that is necessary for proliferation and differentiation?
IL-2
Why does IL-2 only bind to effector T cells and not naive T cells?
It must bind to high-affinity receptor- naive expresses low affinity and upon activated increases the affinity
What is triggered by high affinity binding of IL-2 to an effector T cell?
Clonal expansion
What pharmaceuticals inhibit IL-2 production?
Cyclosporine, tacrolius, and rapamycin
What is the T cells response to recognition of antigen in the absence of costimulation?
They become anergic
True or false: B7 is only expressed on APCs during infection.
True
What is the process of peripheral tolerance development in T cells?
When a self reactive T cell recognized self antigen it becomes anergic; also through action of certain T helpers
What determines the differentiation pattern of an activated CD4+ T cell?
Determined by the local secondary lymphoid milieu set up by the innate immune system
What cytokines induce the differentiation of TH1 cells? What are their signature cytokines produced? What is their function?
IL-12 and IFN-gamma; IFN-gamma; Macrophage activation for bacterial and viral infections