Antibody structure/function (notes/class) Flashcards
T/F Abs are effector molecules of B cells but have NO toxic properties and do NOT themselves destroy invading pathogens
True
What is the 1st component of the classical complement cascade? Describe it
opsonization
Bc Abs also serve as ligands for receptors on phagocytic cells, they promote uptake and destruction of pathogen by phagocytes via opsonization
In some cases binding of Abs to a pathogen prevents binding of pathogen to its host ligand which will prevent infection. What is this action?
neutralization
What are globular proteins produced by B cells and primarily from humoral immune response?
Abs
What are the 5 functions of Abs?
- bind to protein or carbohydrate antigens
- interact with host systems (complement) and cells (macs) to promote clearance of infectious agents
- membrane integrated forms serve as main component of BCR
- block spread of infectious agents in blood and help prevent re-infection at mucosal surfaces
- provide protection from rechallenge by infectious agents
All Ab molecules have a common core structure consisting of what?
2 identical light chains
2 identical heavy chains
What forms the attachment of the light chain(LC) to heavy chain(HC)? Describe these attachments
Attachments are formed by intrachain disulfide bonds
1 of 2 LC to each HC
HC are attached to each other
T/F HC and LC are encoded on separate genes
Ig domains fold how? What helps with this?
Ig domains fold independently and interchain disulfide bonds help form the domains
Which Ig domain is the variable region and the constant region?
Variable region is at the amino-terminal Ig domain and is highly variable between different Abs
Constant regions are very conserved
What domains of all Ab molecules have a similar structure?
Constant (C) domain and variable (V) domain
Where do Abs perform their functions? Where do they encounter there that forces them to use a tertiary structure to withstand these?
in extracellular spaces in the presence of infection
encounter variations in pH, [salt], proteolytic enzymes, other destabilizing factors
tertiary sturcture enables them to withstand these factors and maintain functionality
Describe the shape and bonds of the C and V domains of the Ig
both C and V domains are reoughly cylindrical shape and formed by 2 adjacent B-sheet structures covalently linked by a disulfide bond
Describe how Ig folds are formed
adjacent B-sheets form a Beta barrel motif of proteins and those formed in Ab molecules are called from Ig folds
What is the primary difference between the structures of C and V domains?
V domains are larger and have an extra loop of polypeptide chain
flexible loops of V domains form the antigen-binding domains
What forms the antigen-binding site of each “arm” of an Ab molecule?
localized regions of both HC and LC V domains
Sequence variability is confined to 3 distinct regions. What are they?
- hypervariable - HV1, HV2, HV3
- complementarity-determining region - CDR1-3
Low variability between hypervariability are
- Framework regions (FR1-4)
What happens when the HC and LC are paired in an Ab molecule wrt to the HV regions?
HV regions are brought together creating a single HV site at the tip of each “arm” of the Ab molecule
What can the HV site form?
antigen binding site and complementarity determining regions
Depending on the sequences that form the antigen binding site, what can it bind to?
The region of the antigen that is recognized by the Ab is known as what?
the antigenic determinant or epitope
T/F Abs can bind to portions of molecules that vary in shape and physcial properites
True
What are the functions of Abs? When are they most effective?
Fxn: bind to microbes and to facilitate their destruction and removal from body
Most effective: combat infection are those that bind to surface exposed/accessible moecules of pathogen
The portion of any particular antigen that an Ab binds to is called what?
antigenic determinant or epitope
Abs produced in response to an infection usually have a specificity for epitopes composed of what?
either carbohydrates or proteins
Complex macromolecules have multiple epitopes that can be bound by a separate Ab molecule called what?
multivalent antigens
T/F a multivalent antigen can have a single epitope that is repeated many times
false, or it can have a number of distinct epitopes
Abs that have specificity for chem structures other than carbs or proteins can be produced. These are often involved in allergic rxns and autoimmmune diseases. What are the specific for and what are they not involved in?
Abs specific for DNA are NOT involved in defense against infection but are involved in allergic rxns and autoimmune diseases
What forces are needed to bind Abs to antigens?
non covalent forces (electrostatic forces, H bonding, van der Waals forces, hydrophobic interactions)
What are the antigen binding regions of Ab molecules typically rich in? What forces are they usually found in?
typically rich in aromatic AA
parcipitate in many van der Waals and hydrophobic interactions
The HV or CDR of the V Ig domain of LC and HC come together to form a unique shape. What is found in these regions so what action can occur?
AA side chains that reside in these regions to allow the Ab to bind to spcific epitope
The binding stregnth of any Ab to its particular antigenic determinant is known as what?
binding affinity
T/F ALL non-covalent protein:protein interactions are reversible
true
An Ab that has ____ affinity for an antigen stays bound longer than an Ab that has ____affinity.
High affinity binds longer than Ab with Low affinity
Ab can bind to 2 types of antigenic determinants of proteins. What are they and describe them?
- continuous epitopes (linear) => formed by linear stretch of AA
- discontinous epitopes (non-linear) => formed by AA from different parts of polypeptide brought together in folded protein
Ab molecules are subdivided into 5 different isotypes based on HC. What are the isotypes?
Ig A, D, E, G, M
The amino terminal ends of both the HC and LC contain what regions of the polypeptide chains?
Variable (V) or hypervariable regions
Describe the V and C region of the LC
LC have a single V region and single C region
Describe the regions that make up the HC
1 V region
3 C regions for IgG, IgD, IgA
4 C regions for IgM, IgE
Which Ig have a hinge region? What AA is present in the hinge region?
IgG, IgD, IgA
rich in proline residues
Why is the hinge region important?
it allows flexibility of Ab molecule that enables it to more easily bind to antigenic determinants and/or immune components FcR
What are the 2 types of LC?
kappa and lambda
The kappa and lambda types of LC are present in which Ab?
present in all 5 isotypes of Ab
only, 1 of these LC types is present in an individual Ab molecule
What are the subclasses of IgA? IgG?
IgA1 and IgA2
IgG1-4
What Ab can exist as multimeric structures of Ab molecules?
IgM and IgA
What is a distinct feature of the multimeric IgA and IgM? What is the function of this feature
the J chain or joining chain that is disulfide linked to the tail pieces which are extensions at the C-terminus region of IgA and IgM HCs
tail pieces stabilize IgA and IgM multimers