Block A - lecture 3 Flashcards
(35 cards)
where does the membrane signalling stop ?
phospholipase c gamma one is where the membrane signalling stops and the signal cascade then enters the cytosol of the cell
explain PLC gamma 1
an enzyme and it liberates 2 signalling molecules. PIP2 (Phosphatidylinositol 4,5-bisphosphate) is a membrane phospholipid. PLC gamma one uses PIP2 as a substrate and cleaves the molecule into 2 parts: 1,2 - Diacylglycerol (DAG) and Inositol trisphosphate (IP3)
what occurs if there isn’t a calcium signal ?
T cell will not become activated
what causes the release of calcium ions from the intracellular stores of T cell ?
IP3 signals the release of calcium from the intracellular stores within the T cell , this leads to an increase in the intracellular levels of calcium within a T cell and leads to its activation.
what does DAG activate ?
protein Kinase C
what do anti TCR antibodies activate and what occurs ?
Anti TCR antibodies activate the T cell, and this pulls T cell receptors together called ligation
what occurs once ligation has occurred ?
once the T cells are ligated this leads to an increase in the calcium production. This process is a fast , not slow
does free calcium have much of an effect on T cells alone ? why
The free calcium doesn’t have much of an effect on T cells alone. It requires the calcium to bind to calmodium and this then activates T cells. The calmodium then activates the Calcineurin which is a protein
what is calcineurin and mode of action?
Calcineurin removes the phosphate and this translocates the NFATc to the nucleus and it is now NFATn and it is a transcription factor which directly controls gene expression and DNA.
explain pathway of DAG
DAG activates protein Kinase C. Protein Kinase C activates I kappa B kinase which leads to the phosphorylation of the I kappa B subunit of NF kappa B. This phosphorylation leads to the disengagement of the NF kappa B and it can translocate into the nucleus to become a transcription factor.
Ras/Rac pathway ?
Ras/Rac pathway is a small GTP binding protein. It activates proteins involved in mitogenesis ( cell division). This leads to the activation of MAP and JNK kinases. MAP kinase phosphorylates fos and fos enters the nucleus. JNK phosphorylates jun and this also enters the nucleus. It is these 2 transcription factors that when interaction occurs leads to a pre transcription factor AP-1 complex to form. AP-1 influences gene expression. It is thought that CD28 causes the activation of Ras/Rac pathway
when will T cell division not occur ?
T cell division will not occur is the calcineurin pathway doesn’t occur.
where does the signal start ?
in the membrane which leads to activation of PLC
what generated soluble signal ?
phospholipase C which generated the soluble signal that could enter the cytosol of the cell , this could be DAG or IP3
what allows the kinase or phosphatase activity ?
The DAG activates protein Kinase C , while the IP3 mobilises intracellular stores of calcium. This action allows the kinase or phosphatase activity on a transcription factor , which allows it to enter the nucleus of a cell through translocation and gene expression can be modulated.
what is the late phase of T cell activation ?
gene transcription phase in the nucleus
immediate genes ?
ones that need to be expressed in a very short period of time. These are c – fos and c- myc which are the transcription factors so the signal pathways can occur.
early genes ?
nvolved in the function of the T cell and are expressed up to 6 to 12 hours. These includes IL2 , IL 2 receptor alpha chain and cytokines. IL-2 is important as it is the growth factor for T cell division. Cytokines are needed for the CD4 cell as they are the helper cells .
late genes ?
MHC, adhesion molecules and VLA (very late antigens). These are involved in housekeeping functions.
what is the point of these genes ?
produce a response, T cell proliferation. It is the early genes which expresses IL2 which is critical for the proliferation of the particular T cell that is activated by the pathogen.
what stage do drugs target ?
Drugs can target calcium mobilisation so that the IL2 is not expressed and the T cell does not proliferate.
is the one activated T cell enough to fight an infection ?
the one T cell that is activated is not enough to fight an infection, so once the antigen is recognised the T cell needs to quickly produce clonal cells through expansion to form a mass of identical cells to fight the pathogen.
what is the job of a B cell and how ?
B cells job is to produce antibodies and therefore must recognise a pathogenic antigen and produce an antibody against it.
describe the B cell receptor ?
The B cell receptor has a variable region, and it shows structural similarity to an antibody. The B cell contains antibodies embedded in the membrane it is an sIgM as it is a surface IgM , this can also be an mIgM for membrane.
