What kind of immune response is uniquely adapated for elimination of extracellular pathogens?
The humoral immune response
Scientist that used 2 Fabs and one "tail" fragment (Fc).
Rodney Porter
Scientist that resolved heavy and light chain.
Gerald Edelman
What does Fab stand for?
Fragment antigen binding
What does Fc stand for?
Fragment crytallizable
Where does proteolytic cleavage cut the antibody when pepsin is used?
below the disulfide bonds
Size of heavy chain?
50kD
Size of light chain?
25kD
Total mw of antibody?
>150kD
What constant heavy chain is closest to the variable heavy chain?
CH1
How many amino acids in the light chain constant and variable domain?
~110
The two major light chain constant regions do not determine the ______ of the Ig.
class/isotype
What are the two major classes of light chains?
K and l chains (kappa or Lambda)
Ratio of K to l chains varies with the species
mouse: 95% K; human: __ K
60%
In any one Ig molecule the L chains are always either both K or both l but NEVER..
one K and one l
Size of the C-termini amino acid sequence of 2 heavy chains?
330 of 440 aa
Both the heavy and light chains are composed of how many repeating segments?
110 amino acid
Each immunoglobulin domain has an ______ disulfide bond
intrachain
What chains are disulfide linked?
Heavy and light chain & heavy and heavy chain
What kind of difference talks about the different classes of immunoglobulins?
Isotypic differences
Name for differences of polymorphisms within a population?
Allotypic differences
What kind of difference is epitope specific?
Idiotypic differences
What chain determines the class of Ig?
The heavy chain
What is the class of immunoglobulin if the heavy chain is gamma?
IgG
What is the immunoglobulin if the heavy chain is mu?
IgM
What is the immunoglobulin if the heavy chain is alpha?
IgA
What is the immunoglobulin if the heavy chain is delta?
IgD
What is the immunoglobulin if the heavy chain is epsilon?
IgE
Which immunoglobulins have 4 domains (extra domain)?
IgM & IgE
How is IgA secreted?
As a dimer
What is the only immunoglobulin subclass that can transfer to the fetus?
IgG
What percentage of serum antibodies is IgG?
80%
Which IgG subclass is the largest?
IgG3
Where can IgG subclass structural differences be seen?
In the hinge region
Which IgG subclass is the only one that will react negatively with Papain?
IgG2
What carries IgG across endothelium into extracellular spaces?
FcRB
Which IgG subclass will not activate complement?
IgG4
What percentage of serum antibodies are IgM?
5-10%
Which immunoglobulin is present on the surface of B cells?
IgM
Size of IgM heavy chain?
70kD
What amino acid is the J train of IgM rich in?
Cysteine
How many amino acids in the COOH tail piece of IgM?
18
Function of J chain?
appears to stabilize polymers
Instead of a hinge region, what is there an extra of in IgM?
CH2 domain
What form is IgM in when it is located on the surface of B cells as part of the B-cell antigen receptor?
monomer form
What are the two forms of IgA?
IgA1 or IgA2 (monomer or dimer)
Where is IgA found?
tears, saliva, milk and intestines
IgA does not...
fix complement
What does IgA provide immunity for?
The digestive tract
What form is secretory IgA primarily in?
Dimer form
What component is necessary for IgA secretions?
The secretory component
Polymeric IgA produced by plasma cells located in the submucosa binds to the _____ receptor on epithelial cells
poly-Ig
The poly-Ig receptor is enzymatically cleaved during the transport process and becomes the secretory component of ______
secretory-IgA
Percentage of IgA present in serum?
10-14%
Main location of IgD?
B cell surface
IgD does not....
fix complement
What other immunoglobulin is IgD expressed with on B cells due to RNA splicing?
IgM
Location of IgE in the blood?
Bound to mast cells and basophils
What can compensate for low affinity of antigen-antibody interactions?
high avidity
Strength of one Ab binding site bound to a single antigenic epitope.
Affinity
Strength of multiple interactions between a multivalent Ab & multivalent Ag.
Avidity
Which immunoglobulin has the highest avidity?
IgM
What are the antigen:epitope attractive forces?
hydrogen bonds, hydrophobic, electrostatic & vanderwaals forces
Kabat and Wu showed there are three regions of the L and H chains that show the greatest amount of variability - What are these regions known as?
hypervariable regions/ CDRs
Which regions of antibody are more variable?
The ones that do not interact with the antigen
How many framework regions in the heavy and light chains?
4
CDR1 of light chain?
residues 28-35
CDR2 of light chain?
residues 49-59
CDR3 of light chain?
residues 92-103
About how many amino acids on both CDRs of the light chain and heavy chain?
27
Functional regions of IgG?
CH2 and CH3
Functional regions of IgM?
CH3 and CH4
Which constant heavy chain is not available when Fab sites are fluctuating/moving?
CH2
What heavy chain of antibody will complement bind to?
CH2
What forces CH2 domains to bulge? This will impact the Fc regions ability to perform effector functions.
Carbohydrates
What kind of feedback happens in complement activation to promote phagocytosis?
Positive feedback
Function of Each Domain
VH, VL?
antigen-binding site
Function of Each Domain
CH1, CL?
allogeneic marker
Function of Each Domain
CH2?
Complement-fixing site
Function of Each Domain
CH3?
cell-binding site