L2: Antibody Structure and Function - Miller Flashcards
What is an antibody?
The secreted form of the immunoglobulin produced by a B cell
What are immunoglobulins?
antigen-binding molecules of B cells
What is the cell called that produces antibodies?
Plasma cells - fully differentiated B cells
Is it possible for a plasma cell to produce antibodies with different specificities?
No. Every antibody produced by a single B cell has the exact same specificity for antigen. They can have different classes though via class switching
What is the main gist of the clonal hypothesis?
Bone marrow produced huge variety of B cells with different specificities. When one reacts with its antigen, it produces and differentiates to give rise to the effector cells with the same receptor to terminate the infection.
What is the primary component of the humoral immune response?
antibodies
What type of bonds hold the heavy and light chains together?
Intrachain disulfide bonds
Are heavy and light chains encoded on the same gene?
No. They consist of a series of similar, but not indentical sequences (Domains) called Ig domains
What is the amino-terminal Ig domain of each chain called? What are the other domains called?
Variable region.
Constant regions.
What are immunoglobulin folds?
the Beta-barrels fromed in antibody molecules
What is the primary difference between the structure of C and V domains of antibodies?
V domains are larger and have an extra loop of polypeptide chain. The flexible loops of the V domains form the antigen-binding domains.
What are the regions where sequence variability is confined to in heavy and light chains called?
hypervariable regions (HV1, HV2 and HV3) or complementarity-determining regions (CDR1-3)
What are the regions between HVs (aka CDRs) called?
framework regions (FR1-4)
Which regions of Ab form the Beta-sheets?
the framework regions (Structural)
Which regions form the loops in between the beta-sheets?
hypervariable regions
What is the portion of the antigen that the antibody binds to called?
epitope or antigenic determinant
What is an antigen that has multiple epitopes called?
multivalent antigen
What type of molecules do antibodies usually bind to?
proteins and carbohydrates. (it can bind to others though this often causes allergic reactions and autoimmune diseases)
What type of bonds do antibodies use to bond to antigens?
solely non-covalent forces (electrostatic, hydrogen bonding, van der Waals and hydrophobic interactions). Note that these are all reversible
What type of AA is commonly found in antigen-binding regions of Abs?
aromatic AAs because they can participate in many van der Waals and hydrophobic interactions
What is the binding strength of any antibody to its particular antigenic determinant known as?
binding affinity
What is an continuous epitope? Discontinuous?
(linear) epitope is formed by a linear stretch of AAs.
A discontinuous is non-linear from different parts of a polypeptide that are brought together in a folded protein
What are the 5 different isotypes? What are these differentiations based off of?
IgA, IgD, IgE, IgG, IgM. Based off the heavy chains
How many variable and constant regions do light chains have? Heavy chains?
Light chains have a single variable and a single constant region.
Heavy chains have one variable regions and 3-4 constant regions
What is the hinge region in a heavy chain?
It is an additional feature of IgG, IgD, and IgA that is rich in proline residues and allows flexibility of the Ab molecule that enables it to more easily bind to antigenic determinants.
What are the two types of light chains?
kappa and lambda. They are present in all five isotypes of Ab, but only one is present in any given Ab. (both light chains are identical in an Ab)
What unique feature do IgM and IgA isotypes have?
They can form multimers using a J chain.
What is the secretory component of Abs?
it is a mucosal secretion that is attached to the Ab non-covalently and allows it to transport through epithelial cells.
What is the most abundant immunoglobulin?
IgG (comprises about 85% of Ig in adults)
Which Ig has the longest half-life?
IgG (23 days)
Which Ig molecules can exist as multimers using the J-chain?
IgA and IgM
What would you expect to happen in an IgA deficient individual?
increased incidence of respiratory infections
What does IgD primarily do?
primarily exists as membrane IgD and serves with IgM as an antigen receptor on early B cell membranes to help initiate Ab responses by activated B cell growth
What does IgE primarily do?
most IgE is bound to Fc receptors on mast cells where it serves as a receptor for allergens and parasite antigens. If sufficient, Ag binds to IgE on mast cells and they degranulate, releasing histamine, prostaglandins, platelet-activating factor and cytokines.
Which Ig is important for parasitic infection protection and anaphylactic hypersensitivity?
IgE
What is the principle Ig in anemnestic (memory) immune response?
IgG
Which Ig can cross the placenta?
IgG
Which is the most efficient Ig for fixing complement?
IgM
Where is monomeric IgM found?
on the surface of all naive B cells, where it serves as a receptor for antigen
Can IgM cross into tissue well?
No, because of its large size.
Which Ig is important for immunity to polysaccharide antigens
IgM
What is the idiotype?
The AA sequence in the variable region of an Ab molecule that is the mirror-image of the epitope that the antibody recognizes
What is the Fc portion of the Ab?
interacts with the complement components and with macrophages and NK cells to promote clearance of antigen and activation of subsequent immune responses
Which portion of the Ab is sensitive to proteolytic cleavage?
The hinge region.
What is papain cleavage?
cleavage of the hinge zone to produce 1 Fc fragment and 2 Fab fragments.
What is a Fab fragment?
a cleaved portion of an Ab that contains a single antigen-binding site
What is pepsin cleavage?
cleavage of the hinge zone that produces 1 F(ab)2 fragment with 2 antigen binding sites and a single pFc fragment.
Which binds to antigen with higher affinity: Fab or F(ab)2?
F(ab)2 because it has two antigen-binding sites
Which Ig molecules have subtypes and what are they?
IgG1-4 and IgA1-2
What are the differences between the IgG subtypes?
The hinge region is different
Can a B cell produce antibodies with different antigen specificities?
No, each Ab produced by a B cell has the same antigen specificity
Can a B cell produce Abs of different isotypes?
Yes. They can be signaled to change the constant region of the heavy chain to produce a different isotype to allow maximum versatility of Abs with identical antigen specificity
Which Ig’s have the lowest serum levels?
IgE is lowest, followed by IgD
Which is the heaviest Ig?
IgM at 970 kD
Which Ig’s are important in neutralization?
IgG1-4 and IgA
Which Ig’s are important in opsonization?
IgG1 and IgG3
Which Ig’s are important for sensitization for killing by NK cells?
IgG1 and IgG3
Which Ig’s are important for sensitization of mast cells?
IgE
Which Ig’s are important for activation of complement system?
IgM, IgG 1 and IgG3
Which Ig can transport across epithelium?
IgA
Which Ig can transport across placenta?
IgG1
Which Ig’s can diffuse into extravascular sites?
IgG1-4 and IgA
