lecture 5- T cell response Flashcards
Whats the point of dendritic cells?
There are so many points of infection and its not possible to have lymphoid organs present everywhere. So dendritic cells patrol all the areas and pick up microbes, become an APC, and produce it to T cells
What are the two classes of dendritic cells?
classical- activate T cells
plasmacytoid- activate Type 1 interferons, the cytokine that’s involved in antiviral activity
what generally happens after a dendritic cell finds a microbe.
It ingests the microbe an a lot of the PAMPS and other products bind to PRR causing maturation process to begin. (1) Upregulation of MHCs, B7, iCAM1 as DC travels to lymph node
How do the DCs know where to go?
DCs lose their adhesiveness to epithelial cells and begin to express receptors for chemokine CCR7, causing chemotaxis to lymph node area.
How does a T cell get activated?
2 signal activation
1) - bind to peptide (MHC of APC to peptide and CD4/8 of Tcell
(2) - coreceptors bind (B7 of APC to CD28 of T cell)
What is the point of coreceptor B7?
B7 is the second step in signal activation and is a guard against autoreactivity. What if there is a defective T cell that does not have central tolerance, the B7 is whats needed to ensure that the APC is actually presenting a pathogen.
what is the point of iCAM?
To maximize the response. Integrin LFA on the Tcell binds iCAM on the dendritic cell and allows stable bonding.
How do Tcells proliferate?
The stable adhesion between DC and Tcell via the 2 step activation and iCAM causes upregulation of IL2 activity which stimulates proliferation. IL2 cytokine can be autocrine and paracrine so it can activate not only the t cell bound to the DC but proximal tcells as well
Describe the Tcell signaling pathway once iCAM, MHC, and B7 are all bound to it from DC?
the CD3 and zeta proteins associated with TCR contain ITAM. ITAM becomes phosphorylated by Lck which is associated with CD4/8 receptors. this causes the PLy pathway, Ras/Rac pathway, and PI3k pathway
What 3 main TFs are generated by the Tcell signaling pathways??
NFAT, NFkB, Ap1
(medical): cyclosporine?
PLCy pathway; inhibits Calcineurin
(medical) Rapamycin?
PI3K pathway; inhibits IL2 communication with Akt MTOR
(medical) describe a biochemical pathway for immune suppression?
CTLA4 binds b7 and blocks DC’s b7 from binding to Tcell’s CD28
autoimmune disease
(medical) describe a biochemical pathway for immune enhancement?
block inhibitory PD1 receptor on T cells-immune enhancement.
cancer treatment
What is cross-presentation?
When a dendritic cell phagocytosis a microbe, it usually becomes a MHCII (extracellular) and binds CD4 Tcells. But sometimes the microbe particles can leak into the cytosol of the DC and cause a MHCI reaction, and make the DC bind CD8 T cells
What are Superantigens?
Superantigens are pathogens that trick the immune system and cause systemic drop in BP and apoptosis of Tcells due to massive inflammation by huge cytokine secretion from overactivity of unspecific Tcells.
How do Superantigens work (biochemically)
they bind MHCII without being ingested by APC, and then they non-specifically bind variable regions of TCR, inducing a cytokine response. Many T-helper cells are unspecifically activated and secreting inflammatory cytokines causing drop in BP, this in turn causes apoptosis of many Tcells
What types of T-helper cells are there? How is one different from the other 3?
Th1, Th2, Th17, TfH
Th1,2,17 are all helper Tcells that respond to unique types of extracellular microbes.
TfH enhances Bcell antibody production in lymph follicles. TfH is different than the others because it never leaves the peripheral lymph organs.
How do Naïve T cells go from blood to lymph nodes
Naïve T cells express CCR7, L-selectin and the integrin LFA-1 to direct their trafficking.
–> L-selectin on T cells with L-selectin ligand on the HEVs.
LFA-1 integrin on T cell binds integrin ligand ICAM-1 on –> the HEV
to cause slowing down and rolling
How does the T cell leave the lymph node?
high level of S1P in blood and lymph keeps expression of the S1P receptor LOW on the T cells.
naïve T cell enters the lymph node (lower S1P levels), receptor expression begins to increase.
No MHC activation? the T cell (with higher receptor expression) follows the increasing S1P gradient out of the lymph node.
MHC activation?: S1P receptor levels
suppressed for days. T cell activate, proliferate and differentiate. S1P receptor levels begin to rise, the cells lose expression of CCR7 and L-selectin, and the activated effector T cell exits along the S1P gradient
(medical) What is a treatment for Multiple Sclerosis?
S1P receptor inhibitor
