Immunology 2: Antibody Structure Flashcards
What is an antibody?
the secreted effector molecules of B/plasma cells that bind to specific ligands on surfaces of pathogen; then serves as the ligand for phagocyte receptors
All antibodies have a common core structure that consists of what?
2 identical light chains and 2 identical heavy chains; the heavy chains are attached to each other and each light chain is attached to a heavy chain
What is an immunoglobulin domain?
a sequence of amino acids in an antibody sequence, about 110 residues long; can be either a variable and constant domain
The unique tertiary structure of antibodies enables them to do what?
withstand highly variable and potentially destabilizing extracellular conditions while maintaining functionality in the presence of infection
What is the primary difference between the structure of the C and V domains of immunoglobulin domains?
V domains are larger and have extra loops of polypeptide chain
What is common to the structures of both C and V Ig domains?
they are roughly cylindrical in shape; formed by 2 adjacent beta sheet structures linked by an intrachain disulfide bond
What is an immunoglobulin?
the antigen-binding molecule (effector molecule) of B cells; termed antibody once secreted
The two identical heavy chains in an antibody monomer are joined together by ____ bonds.
disulfide
The V domains of heavy chains are adjacent to the V domains of light chains and form what?
the variable domains come together to form the unique antigen binding site of of each antibody molecule; this makes 2 antigen binding domains in each monomer
What is the significance of the carboxy terminus of the heavy chains of the antibody monomer?
they bind to antibody receptors, or Fc receptors, expressed on the surface of immune cells; this is one way the antibody bridges the innate and acquired immune systems
Hypervariable regions of both heavy and light chain V domains are located alongside low variability regions known as ____.
Framework (FR) regions
Framework regions of V domains form _____ that provide the structural framework of the domains while hypervariable sequences form _____ that correspond to the loops between beta sheets.
beta-sheets; loops
What is the complementarity-determining region?
this is the hypervariable site of a V domain within an antibody that serves as the antigen-binding site
What is an antigenic determinant, or epitope?
the portion of any particular antigen that an antibody binds to. Typically composed of glycoproteins, polysaccharides, glycolipids and proteoglycans.
What is a multivalent antigen?
pathogenic molecule that has more than one epitope and can be bound by multiple antibodies; these multiple epitopes can be repeating or distinct
Most antibodies have specificity for what types of chemical structures?
carbohydrates or proteins
Binding of antibodies to antigens is based solely on non-_____ forces.
based on non-covalent forces (electrostatic, van der Waals, H-bonding, hydrophobic interactions)
What determines binding affinity of an antibody binding to its antigenic determinant?
the binding strength of the antibody to antigenic determinant
To what does binding avidity refer?
the combined strength of all antigen binding domains of an antibody bound to its antigenic determinant simultaneously
A continuous epitope is formed by what?
a continuous, linear stretch of amino acids found on an antigen
A discontinuous epitope is formed by what?
portions of an antigen that come together to form a discreet formation; ex: amino acids in a protein antigen are adjacent when the protein is in its native form
Antibodies can be divided into ____ different isotypes based on the type of ____ _____ that is found in the antibody.
5; heavy chain
What is the hinge region of the heavy chain?
region of IgG, IgD, and IgA heavy chains that is rich in proline residues; allows flexibility of the antibody molecule in order that it may bind more easily to antigenic determinants or immune components
What are the 5 types of heavy chains?
Ig A, D, E, G, M (greek letters though)
What are the two types of light chains?
lambda and kappa
What is the J chain and what is its function?
feature of multimeric IgA and IgM; 15kD polypeptide that is disulfide linked to the tail-pieces (C-term extensions of IgA and IgM heavy chains); functions to stabilize IgA and IgM multimers - these are the only antibodies that will form multimers
CH2 Ig domain contains the determinant that ____ ____ binds to when initiating the classical complement cascade.
complement C1
What functional region of antibody binds to complement proteins and Fc receptors on various WBCs, and consists only of heavy chain domains?
The Fc region/fragment (the bottom of the antibody Y shape)
What is the Fab region/fragment of the antibody?
contains one antigen-binding site (each one half of the ‘V’ tops of the antibody Y shape)
The beta barrel tertiary structure of light-chain C domains is stabilized by what?
a single interchain disulfide bond
What separates the light chains C and V domains?
stretch of amino acids without secondary structure
IgM is always secreted in ____ form, meaning it has how many antigen binding domains?
pentameric; 10
IgA can be secreted in what form(s)?
monomeric, dimeric, or trimeric; most predominant/important is dimeric
What is the primary function of IgA?
to neutralize pathogens and prevent them from colonizing mucosal surfaces
Which Ig is the largest and why?
IgM, because it’s secreted as a pentamer
Mast cells use which Ig as antigen-specific receptors?
IgE (this is the primary role of IgE)
Which Ig(s) has the longest half-lives?
IgG subtypes
What is neutralization?
preventing a pathogen/toxin from interacting with cell surface receptors which would facilitate colonization or entry into host cells
Which Ig is actively transported into mucosal secretions to neutralize pathogens?
IgA
IgG is actively transported across what barrier during pregnancy to passively protect the infant for several months after childbirth?
placenta
What two Igs leave the vasculature to act in the extravascular space?
IgA (a little) and IgG
Antibodies that have specificity for chemical structures other than carbohydrates and proteins are involved in what adverse event?
allergic reactions, autoimmune disease
Would a monovalent antigen or multivalent antigen be more difficult for an antibody to bind?
monovalent, because basically there are fewer sites to recognize; the more and more different epitopes there are the easier for the immune system to recognize and bind the antigen
T cell receptors only recognize antigens bound to what?
MHC molecules
Would a monovalent antigen or multivalent antigen be more difficult for an antibody to bind?
monovalent, because basically there are fewer sites to recognize; the more and more different epitopes there are the easier for the immune system to recognize and bind the antigen
Can an antibody molecule contain two different types of light or heavy chains?
No. The single, unique type of chain is what differentiates them.
Which antibody type is most predominant in lymph?
IgG - it diffuses most into extravascular spaces, then is picked up by the lymph system
Which Ab isotype is most involved in recognizing viral pathogens?
IgG - involved in sensitizing NK cells
What are the different antibody isotypes (and number of subtypes) that can be secreted by plasma cells?
IgA (2), IgD, IgE, IgG (4), IgM
Which antibody type is most predominant in lypmh?
IgG - it diffuses most into extravascular spaces, then is picked up by the lymph system
Which antibody isotype has highest potential for binding avidity to its cognate antigenic determinant?
IgM - because it is a pentamer, all 10 can bind the determinant simultaneously
Which antibody is responsible for anaphylactic hypersensitivity?
IgE
Which antibody is responsible for protection against parasitic infection?
IgE
Which antibody can most efficiently “fix” complement?
IgM
Which antibody isotype has highest potential for binding avidity to its cognate antigenic determinant?
IgM - because it is a pentamer, all 10 can bind the determinant simultaneously
Which portion (Fc, Fab) of antibody:antigen complexes can bind to complement, initiating the complement cascade?
Fc
Which portion of antibody molecules can facilitate delivery of antibody to sites they would not reach without active transport? (sites include mucous, tears, milk, fetal blood circulation).
Fc portion
Maternal isotypes of which antibody are responsible for keeping infants and young children well?
IgG - transported across placenta
IgA - transported via breast milk
