Recognition and Response Flashcards
What bonds occur in receptor-ligand binding?
multiple noncovalent bonds
Is a non-covalent bond irreversible?
no- bond can be broken
What is the measure of ligand binding strength?
Kd = Dissociation constant
What are the 2 requirements for receptor-ligand binding/ cell to become activated?
-sufficient binding energy
- for sufficient time
What are the 3 types of receptor-ligand interactions?
(noncovalent)
Hydrogen bond
Ionic bond
Van der waals/ Hydrophobic interactions
How strong must each bond be for receptor-ligand binding?
- each individual bond can be weak
- total binding affinity strong
How can a strong binding affinity be achieved?
many weaker bonds occur between receptors/ ligands
= great cumulative bond strength
Is binding affinity the strength of one bond?
no- cumulative bond strength
What is a ligand called with only one binding site?
- 1 receptor/ 1 ligand = specific
Univalent
What is a ligand called with many binding sites?
Multivalent
What increases the avidity of receptor-ligand interactions?
Multivalency
What is the strength of an individual bond called?
Affinity
What is the combined strength of binding multiple interactions called?
Avidity
Does weak affinity mean weak avidity?
no- interactions can still have high overall avidity
- individually weak, strong together
What is it called when the receptor-ligand interaction can occur at 2 sites?
Bivalent interaction
What is induced by ligand-receptor binding?
molecular change in receptor
- receptor alterations
What is the result of receptor alterations?
(after ligand-receptor binding)
= intracellular cascades
- enzyme activation
- changes in intracellular locations of molecules
Why is cluster formation favoured?
conformational change
- harder to disrupt interaction
What are some receptor alterations induced by ligand-receptor binding?
- conformational
- dimerization/ clustering
- membrane location
- covalent modification
What is another term for clustering?
Aggregation
What impact does aggregation due to ligand binding have on Kd?
enhances it (stronger)
What do cell-cell interactions rely on to maintain contact over long periods of time?
binding affinity
How are Kd and binding affinity related?
inversely
What does extended receptor-ligand contact facilitate?
- signal transduction
- exchange of cytokine signals
What may occur upon extended receptor-ligand binding?
cytoskeletal organization
What is the relative Kd of low-affinity ligand binding?
low affinity = higher Kd (inverse)
What is the relative Kd of high-affinity ligand binding?
high affinity = lower Kd (inverse)
What do immune receptors have?
Immunoglobulin domains
What are the 3 types of immune receptors?
Transmembrane
Cytosolic
Secreted
What is a secreted immune receptor?
Antibody
What kind of immune receptor has an anchoring point for the ligand?
Transmembrane
What happens to an immunoglobulin lacking the carboxyl terminus transmembrane segment?
secreted (lacks anchor point)
What is a feature of secreted immunoglobulins? (antibodies)
Hydrophilic segment
- likes to be soluble
What is the overall strength of the binding recognition between the ligand and the receptor?
Binding affinity
Why are antibodies secreted?
lack an anchor point within membrane
- lack carboxyl terminus transmembrane segment
Where is the transmembrane domain located?
carboxyl terminus
What is associated with the transmembrane domain in a BCR?
- cytosolic segment
- hydrophobic segment
- spacer
What happens when a B cell becomes activated?
secretes antibodies
How does a B cell become activated/ secrete antibodies?
goes from membrane-bound/ transmembrane receptor to secreted = antibody
What are the antibodies of BCR’s defined by?
Specificity
What do BCRs contain?
antibody of defined specificity
What is the specificity of TCRs?
peptides derived from APC degraded antigen
- presented on MHC molecules
What receptor recognizes degraded antigen from APC on MHC molecules?
TCR
What are the T-cell co-receptors that define different subsets of T-cell function?
CD4/ CD8
What defines the different subsets of T cell function?
T cell co-receptors = CD4/ CD8
What kind of protein is an antibody?
quaternary
How many chains does an antibody have?
= quaternary protein
2 identical heavy chains
2 identical light chains
How is antigen specificity created?
interaction between light/heavy chains variable regions
What chains are the interior V in an antibody?
heavy chains
What chains are the exterior V in an antibody?
light chains
Interaction between what is responsible for antigen specificity?
variable regions of light/ heavy chains
Interaction between what is responsible for antibody effector activity?
constant regions of heavy chain
How many parts do the heavy chains have?
4
How many parts do the light chains have?
2
What are some examples of antibody effector activity?
phagocytosis/ complement fixation
What part of the antibody allows the receptor to move?
Hinge
What 3 regions of amino acids are found in variable heavy/ light chains? (VH/VL)
Hypervariable
What forms the antibody binding site?
3 hypervariable regions coming together
What are the hypervariable regions of VH/ VL called?
Complementarity-determining regions
What are the 3 complementarity-determining (hypervariable) regions?
CDR1/ CDR2/ CDR3
- each in VH/ VL
Why is high variability important?
recognize many ligands/ antigens
What is interspersed near each CDR?
What does it do?
invariant amino acid
- forms framework region
What is the framework region responsible for?
folding of CDRs to form antibody-combining site
What determines the antibody isotype?
constant region
What are the distinct classes of antibodies called?
Isotypes
What are the 5 heavy chain isotypes of antibodies?
IgA/ IgD/ IgE/ IgG/ IgM
- alpha/ delta/ epsilon/ gamma/ mu
What are the 2 light chain isotypes of antibodies?
kappa
lambda
What identifies the 5 distinct classes of antibodies?
antiserum to constant region of heavy chain
What antibody is a pentamer?
IgM
What antibody has disulphide bonds to connect the 5 antibodies?
IgM
What antibody is a dimer?
IgA
How is the IgA dimer connected?
J chain
What antibodies look similar but different hinge regions?
IgG/ IgD
How can you differentiate IgG/ IgD hinge regions?
IgG- 2 bonds
IgD- 1 bond
What does it mean if you see a transmembrane domain?
not secreted
What do antibody molecules form a BCR complex with?
molecules involved in signal transduction
What molecules transduce signals via immunoreceptor tyrosine-based motifs? = ITAMs
Iga/ IgB (alpha/ beta)
What are ITAMs?
immunoreceptor tyrosine-based activation motifs
What molecules transmit/ relay signals to cell interior?
CD19/ CD81/ CD21
What is any event that instructs a cell to change its metabolic/ proliferative state?
Cellular signal
How are signals usually generated?
binding of ligand to complimentary cell-bound receptor
What does increasing/ decreasing expression of a receptor for a ligand do?
cell becomes more/ less susceptible to actions of ligand
How can a cell become more/ less susceptible to the actions of a ligand?
increasing/ decreasing receptor expression for ligand
What often induces a change in transcriptional program of target cell?
cell signaling
Where does integration of all signals received by a cell occur?
molecular level inside cell
What initiates signalling in B/ T cells?
antigen-mediated receptor clustering
What is often a result of receptor clustering?
dimerization/ multimerization
Where are clustered receptors localized?
in lipid rafts
What allows movement of clustered receptors/ strengthened bond/ stronger interaction?
localization in lipid rafts
What part of the antibody binds the ligand?
variable chain
What immunoglobulin has a similar hinge region to IgA (dimer version)?
IgD
What is CR2 also known as?
CD21
What are the 5 major steps cell signalling?
- ligand binds receptor
- adaptor recruitment
- phosphorylation
- activation
- transcription
