Antibody Isotypes and Immune Response Flashcards
what are the similarities between the 5 isotypes?
- globular proteins
- at least one Fab and one Fc domain
- carbohydrate groups attached to their constant regions
what are some differences between the isotypes?
- 3 exist as a monomer
- IgA exists as a dimer
- IgM exists as a pentamer
- IgM and IgA each have a J-chain and IgA as a protein covering over the Fc regions (secretory component)
how are isotype designations characterized by?
heavy chains
IgM= μ chain, IgG= γ chain, IgA- α chain, IgD= δ chain and IgE= ε chain
which is the smallest monomer of the isotypes and represents 80% total immunoglobulins?
IgG
what is the half-life of IgG?
23 days
where can IgG be found?
blood, lymph fluid, peritoneal fluid, cerebrospinal fluid and during human pregnancy found mammary milk and maternal IgG can cross the placenta into fetal circulation.
true or false: IgG is a strong at complement activation and agglutination
false: weak
IgG has moderate activity in __ receptor phagocytosis and __ cell
killing.
Fc
NK
what is IgG highly effective against?
viruses, bacteria, and toxins
what branches out of the CH2 of IgG?
carbohydrate functional group
What does FcγR binding initiate?
opsonization
what does C1q binding initiate?
complement activation
what is FcRn?
neonatal receptor linked to maternal passive immunity
which is the largest isotype?
IgM
how many monomers is IgM composed of?
5
each monomer of IgM has a valence of what?
2
why does IgM more typically have a valence of 5?
due to conformational restrictions when they are bound to antigens
true or false: in rare cases, IgM can exist as a hexamer
true
why is IgM restricted to the intravascular spaces?
due to its large size
what is the first immunoglobulin produced when naïve B cells are activated?
IgM
what is the half-life of IgM?
5 days
what is IgM excellent in activating?
complement, agglutination, and precipitation
what are IgM most effective against?
extracellular bacterial infections and minimally effective against viral infection
which isotype is a secretory immunoglobulin and a dimer?
IgA
where can IgA be found?
secretions
- tears
- saliva
- mucous
- sweat
what is the valence of IgA?
4
describe the linkage of IgA
a J chain that links the two IgA monomers and a secretory protein component that protects it from rapid digestion in the secretions.
what is the half-life of IgA?
5.5 days
as a dimer, what is IgA effective at?
- agglutination
- potent antiviral activity
- antibacterial activity when coupled with secretory lysozyme
where does IgA play a major role in immune defense?
mucosa level of respiratory and GI tract
what is unique about IgA once produced in its dimeric form?
it lacks secretory protein
what must IgA do in order to cross the epithelial cells into the mucosa?
must bind to poly Ig receptor on the intestinal cells
the secretory protein facilitates ____________ of the IgA antibody transferring it through the epithelial cell to the mucosa for release
transcytosis
Upon release through the epithelial cells, a long fragment of the secretory protein remains bound to the __ portion of both monomers of IgA as the secretory component to protect it from digestion in the secretions.
Fc
since the secretory protein covers the
Fc portions of the monomers of IgA, what activation is blocked?
complement and Fc-mediated opsonin activity
why is the monomer IgD no well characterized?
because of its relatively low concentration (~0.2 % of total Ig) in the body and its role has not been well defined
what is the half-life of IgD?
2.8 days
what surface is IgD bound to?
mature B cells that are most likely naïve
what is the believed function of IgD?
eliminating autoreactive B cells
what is the half-life of IgE?
2 days
where is IgE found?
bound to mast cells, basophils in saliva and nasal secretions
why is IgE found in such low concentrations?
because of ow rate of synthesis and high affinity for binding its Fc (Fc) to the receptor (Fc receptor) on mast cells and basophils
why is IgE found in such low concentrations?
because of ow rate of synthesis and high affinity for binding its Fc (Fcε) to the receptor (Fcε receptor) on mast cells and basophils
what happens when the antigen binds to IgE on mast cells?
cause them to degranulate releasing potent pre-formed inflammatory mediators that can have both local and systemic effects
why is IgE referred to as immediate hypersensitivity and reaginic antibody?
the rate of IgE-mediated immune response is very fast and can be detrimental to the host.
what does IgE have a beneficial protective role against?
select parasites, helminths, in particular round worms, Ascarids.
what refers to the differences based on constant heavy chains?
Isotypic or class differences
which sub-isotype is a strong activator of complement?
IgG3
which two sub-isotypes are weak at complement activators?
IgG1 and 2
which sub-isotype doesn’t activate complement at all?
IgG4
define allotypes
slight genetic differences in an antibody
that is unique to an individual
what does idiotype refer to?
the specific Fab binding site defined by the VL-VH peptide chains
what is the purpose of the specific Fab binding site defined by the VL-VH peptide chains?
the random substitution of amino acids in these hypervariable regions that define the structural confirmation of the antigen binding or antigenic groove, which in turn determines the specific antigenic epitope that it can recognize
what does the B cell rely on to function as a signal transducer to enhance signal and initiate cell replication?
surface protein receptors or mediators since the BCR does not have a transmembrane domain
what are two signal transducers of the B cell?
CD21 and CD19
If the immunoglobulin to be produced is an IgM
antibody, then how or when do the other classes of antibodies become produced?
isotype switching
when does isotype switching occur?
during B cell replication also called clonal
proliferation and is mediated by T cells
what happens during isotype switching?
T cells through direct cell-cell contact and the secretion of select cytokines, direct the replicating B cell to change the heavy
chain production from a μchain (IgM) to a γ chain (IgG) as an example
what is a primary immune response?
a first vaccine given to an individual that has never been exposed to the pathogen
what is the latent period?
7-10 delay in IgM antiobdy production
what is the exponential phase?
modest increase in antibody production
what is the steady state?
antibody production and degradation are in an equilibrium
what causes the rapid decline after a small peak in vaccine antibody response?
antibody production ceases and antibodies degrade
what would indicate immunologic memory in a vaccine antibody response?
After 14-21 days, a booster vaccine is administered. This time, the latent period is much shorter (i.e. < 3 days) although, the IgM curve is still modest. The IgG curve also has a short latent period (4-5 days), but a robust exponential phase and a broad plateauing steady state
What causes this significant increase in antibody response and titer?
the primary vaccine served to prime the host’s B cells and allow for clonal expansion, both
effector B cells and memory B cells.
what is the result of the secondary booster?
to expand and increase both effector B cells
(i.e. plasma cells) and memory cells
true or false: The more clones capable of responding, the greater the response
true
what is affinity maturation?
during clonal expansion, B cells can competitively alter or tweak their Fab binding sites to enhance affinity for the antigen epitope (i.e. strengthen binding).
when is the TCR activated in regards to surface proteins?
when it recognizes the linear epitope presented by an MHC molecule
