I2 Flashcards
Antibodies are the effector molecules (globular proteins) produced in LARGE (not small) quantities by __ cells
B. Specifically plasma cells.each antibody produced by a single B cell has the exact same specificity for antigen
What do antibodies do?
they simply bind to specific ligands on the surface of pathogens. These PROTEINS have no toxic properties and do not themselves destroy invading pathogens. Because antibodies also serve as ligands for receptors on phagocytic cells, when they bind to a pathogen they promote uptake and destruction of the pathogen by phagocytes (opsonization)
Additional roles of antibodies.
In addition, some isotypes of antibodies serve as ligands for the 1st component of the classical complement cascade (opsonization). Finally, in some cases binding of antibodies to a pathogen (or pathogen-derived toxin) prevents binding of the pathogen (or toxin) to its host ligand, thereby preventing infection or toxicity (neutralization).
Describe the structure of antibodies.
All antibody molecules have a common core structure that consists of two identical “light chains” (approx. 24kD), and two identical “heavy chains” (approx. 55 or 70kD). One of the two light chains is attached to each heavy chain, and the heavy chains are attached to each other; these attachments are formed by intrachain disulfide bonds.
T or F. heavy and light chains are encoded on the same genesWhat are lg domains?
F. They are encoded on separate genesheavy and light chains consist of a series of similar (not identical) sequences (domains); about 110 residues in length (Ig domains)immunoglobulin (Ig) domains fold independently, interchain disulfide bonds help form the domainsthe amino-terminal Ig domain of each chain (variable region) is highly variable between different Abs; the remaining domains are conserved (constant regions)
Note on domain structure.
the constant (C) domains and variable (V) domains of all antibody molecules have a similar structure; it is important toremember that Abs perform their functions in extracellular spaces in the presence of infection, where they encounter variations in pH, salt concentration, proteolytic enzymes, and other potential destabilizing factors; their unique tertiary structure enables them to withstand these environmental factors and maintain their functionality
Describe the shape of the C and V domains of antibodies.
both C and V domains are a roughly cylindrical shape and are formed by two adjacent β-sheet structures that are covalently linked by an intrachain disulfide bond
the adjacent β-sheets of C and V domains form structures known as a _____.
a β-barrel or β-sandwich (a β-barrel is a common secondary structural motif of proteins)
B-barrels formed in antibody molecules are called?
immunoglobulin folds
What is the primary difference between C and V domains?
V domains are larger and have extra loops of polypeptide chain
The extra loops of polypeptide chain in the V domains form what?
the flexible loops of V domains form the antigen-binding domainsABDs are found in located regions on BOTH the heavy and light chains
A variability plot in which the amino acid sequences of the V domains of many heavy and light chains have been compared, revealed that sequence variability in confined to 3 distinct regions within these variable domains. What are they?
- hypervariable regions (HV) are designated HV1, HV2, and HV3 (or complementarity-determining regions CDR1-3).2. the low variability regions between these hypervariable regions are known as framework regions (FR1, FR2, FR3, and FR4)
What do the framework regions of the V domains (FR1-FR4) form? What about the hyper variable (HV) sequences
the B-sheets that provide the structural framework of the domains, while the hypervariable sequences correspond to the loops between the β-sheetstherefore, the hypervariable regions are localized to a particular surface of the immunoglobulin molecule
How do the HV regions of the light and heavy chains in an antibody interact?
when the heavy chains and the light chains are paired in an antibody molecule, their hypervariable regions are brought together, creating a single hypervariable site at the tip of each “arm” of the antibody molecule. This conjoined hyper variable site forms the antigen-binding site
The antigen binding regions of an antibody molecule are aka?
the idotype of the antibody
What is idiotype?
term to describe the 3D or tertiary structure of the antigen binding site of an antibody. The idiotype is essentially the shape of the antigen-binding site that accommodates the shape of a particular antigen
T or F. Each antibody molecule has only a single idiotype. Why or why not?
T. because both of the antigen-binding sites of any antibody monomer are identical, and therefore, they have an identical shape.
The region of the antigen on an invading micro-organism that is recognized by the antibody by its HV regions is called?
an antigenic determinant or EPITOPE
Again, what is the function of antibodies?
the function of antibodies is to bind to microorganisms and to facilitate their destruction and removal from the body
Antibodies produced during INFECTION usually have specificity for what kinds of epitopes?
those that are composed of eithercarbohydrate or protein (remember, the surface of pathogens typically are composed of glycoproteins, polysaccharides, glycolipids, and proteoglycans)
What are multivalent antigens?
Antibodies typically have specificity for epitopes that are composed of carbs or proteins. Complex macromolecules like these typically have multiple epitopes, each of which can be bound by a separate antibody molecule (but those antibodies don’t necessarily have to be distinct)
T or F. a multivalent antigen can have a single epitope that is repeated many times, or it can have a number of distinct epitopes
T. Repeat: a multivalent antigen can have a single epitope that is repeated many times, or it can have a number of distinct epitopes. What is the significance of this?Most pathogens are multivalent
Can antibodies be produced that have specificity for epitopes that care composed of things other than carbs or proteins? If so, what are they typically used for?
Yes. Such antibodies are involved in allergic reactions and autoimmune diseases and are not involved in defense against infection (e.g. antibodies specific for DNA are characteristic of systemic lupus erythematosus)
The binding of ABs to antigens (via what regions on each?) is based solely on what kinds of forces?
non-covalent forces (electrostatic forces, hydrogen-bonding, van der Waals forces, and hydrophobic interactions)
How are van der Waals and hydrophobic interactions between ABs and antigens produced? In other words, what characteristic of ABs allows for this to occur?
the antigen-binding regions of antibody molecules are typically rich in aromatic amino acids which can participate in many van der Waals and hydrophobic interactions
How do the HV regions of light and heavy chains come together? What do they form to facilitate antigen binding?
the hyper variable regions (orcomplementarity-determining regions or CDRs) of the variable Ig domain of the light and heavy chains come together to form a unique shape that, together with the amino acid side chains that reside in these regions, allows the antibody to bind to a specific epitope; The HV regions of the heavy and light chain come together to form pockets, grooves, or extended surfaces that allow them to bind to their specific antigen.
T or F. it is possible that there could be several structurally distinct antibodies that could bind to the exact same epitope
T; however, each of these antibodies could bind to the epitope with different binding strengths
The binding strength of any antibody to its particular antigenic determinant is known as?
the binding affinity. NOTE: it is important for you to remember that all non-covalent protein:protein interactions are reversible; an antibody that has high affinity for an antigen stays bound longer than an antibody that has low affinity
