Chapter Three Receptors And Signaling : B And T-cell Receptors Flashcards
Antigens
Foreign molecules that signal the presence of no self entities to immune system
Receptor protein
One of major routes by which a cell interprets its surroundings is through the binding of signaling molecules, or ligands, to these proteins
Cytokines
Small molecules that communicate among various populations of immune cells
Chemokines
Specialized cytokines that induce chemo-attraction or -repulsion
Cellular signal
Any event that instructs the cell to change its metabolic or proliferative state
How are signals usually generated
By the binding of a ligand to a complementary cell-bound receptor
What types of ligands are there
Soluble molecule, or peptide, carbohydrate or lipid
How does ligand travel
Through bloodstream or lymphatics
What kind of molecular change can a ligand induce in a receptor
Conformation change
Dimerization or clustering
Change in location in membrane
Covalent modification
What do ligand caused receptor alterations set off
Cascades of intracellular events like activation of enzymes, changes in intracellular location of important molecules
What is usual end result of cellular signaling
Change in transcriptional program of target cell
Hoe does ligand bind to receptor
By noncovalent chemical linkages
Association constant
The ratio of k_1/k_-1, or association rate constant/dissociation rate constant. A measure of affinity of the receptor ligand pair. The relationship between the concentration of reaction product and the product of the concentration of reactants. (Ka). The higher the Ka, the higher the affinity of the interaction.
Dissociation constant, Kd
Reciprocal of association constant. The lower the Ke, the higher the affinity of the interaction.
What are multi alert receptors
They have more than one ligand binding site per molecule
What is the benefit of multivalency
Noncovalent binding interactions are inherently reversible. The ligand spends some of its time on receptor and some of its time off. When more than one binding site is involved, it is less likely that all of the receptor sites will be simultaneously in the off state so that ligand is released.
Avidity
Overall strength of the collective binding interactions that occur during multi alert binding. This can be accomplished with a molecule with multiple binding sites or a receptor that can create a cluster in membrane,
How do we measure affinity of receptor-ligand interactions
Techniques such as equilibrium dialysis or surface plasmon resonance.
Why is it important that receptors are in low affinity form and are expressed on as needed basis
By waiting before expressing high affinity cytokines receptors, lymphocyte conserves energy and prevents accidental initiation immune response to an irrelevant gene,
How are cytokines released exactly where they are needed
Antigen receptor signaling can induce redistribution of the microtubules organizing center (MTOC) within the activated T cell. This causes redistribution of secretory organelles within th T cell cytoplasm, so that cytokines made by the T cell are secreted in the direction of thr T cell receptor, which in in turn is binding to the antigen-presenting cell
Vectorial redistribution of the secretory apparatus
Process that helps cytokines be secreted directly into space between. Activated T cell and antigen presenting cell.
Where are cytokines most concentrated
At cellular interfaces. So, where two cells meet.
Signal transduction
Molecular route by which a ligand receptor interaction is translated into a biochemical change within an affected cell.
Upstream components of a signaling pathway
Components closest to the receptor
Downstream components of signaling pathway
Those closest to the effector molecules that determine the outcome of the pathway
Common features of signaling pathways
Conformational changes in or clustering of the receptor
Some receptors require receptor associated molecules to signal cell activation
Ligand-induced receptor clustering can alter receptor location
Tyrosine phosphorylation is an early step in many signaling pathways
Adapter proteins gather members of signaling pathways
Phosphorylation on serine and threonine residues
Phosphorylation of membrane phospholipids
Signal induced PIP2 breakdown by PLC causes an increase in cytoplasmic calcium concentration
Ubiquitination may inhibit or enhance signal transduction
What does conformation change in receptor result in
Receptor Dimerization. In cytoplasmic regions of receptors, there is a lot of tyrosine kinase activity that results in reciprocal phosphorylation of the cytoplasmic region of each of the receptor molecules by its dimerizarion
What is clustering
When receptors aggregate into multimedia complexes and move into a specialized membrane region.
What happens when receptor doesn’t have inducible enzyme activities built into it
Receptor needs help from intracellular receptor associated molecules to bring about signal transduction.
Immuno-receptor tyrosine activation motif (ITAM)
Recurrent sequence motifs found on many signaling proteins that become phosphorylated following signal transduction through the associated receptor. This allows docking of adapter molecules that facilitate initiation of signaling cascade.
Lipid rafts
Specialized regions of the lymphocyte membrane into which receptors move after attaching to ligand
Tyrosine phosphorylation event is important because
It can initiate a signaling pathway
Src-family kinases
Family of enzymes to which many of tyrosine kinases that initiate BCR and TCR activation belong
Which kinases are critical to T cell activation
Lck and Fyn
Which kinases are critical to B cell activation
Lyn, Fyn, and Blk
In what two ways are Src-family tyrosine kinases regulated
The enzymes exist in a closed conformation when they are inactive
A phosphorylated tyrosine inside is bound to an internal SH2 domain
How can tyrosine phosphorylation bring about changes in a signaling pathway
Can induce a conformational change
Can permit other proteins to bind
Adapter proteins
Mediate reversible interactions between proteins caused by signaling events
Protein scaffold
Structural framework of adapter proteins for interaction among members of a signaling cascade
Common domains in adapter proteins functioning in immune system
SH2
SH3
PH
SH2 domain
Binds to phosphorylated tyrosine residues