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Ab Structure and B cell Diversity
8.1 at 8 by Dr. Sturtevant
54
Immunology
Professional
08/01/2011

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Cards

Term
What antibodies do naive B cells express?
Definition
IgM and IgD (slide 30 of this powerpoint)
Term
For IgG, how big is the heavy chain? the light chain?
Definition
50, 25 (150 total for antibody)
Term
Where is the N terminus of the heavy chain? the C terminus?
Definition
N terminus is on the variable region, c terminus is on the constant region
Term
Why is it advantageous to have a "hinge region" on an antibody
Definition
hinge region allows flexibility so antibody can bind to a diverse arrangement of two antigens
Term
How many segments make up the C domain?
Definition
3-4 depending on the specific isotype (3 in IgG, IgD, IgA; 4 in IgM and IgE)
Term
How many globular regions and how many beta sheets in Ig?
Definition
three globular regions and 2 beta sheets
Term
How are the beta sheets held together in an Ig?
Definition
hydrophobic interactions and disulfide bonds
Term
Heavy chain of IgG is known as _____.
Definition
γ
Term
Heavy chain of IgM is known as ______.
Definition
µ
Term
Heavy chain of IgD is known as ____.
Definition
δ
Term
Heavy chain of IgA is known as ____.
Definition
α
Term
Heavy chain of IgE is known as ___.
Definition
ε
Term
Name the two isotypes of light chains.
Definition
κ and λ
Term
Name the class of antibodies that are tetramers.
Definition
IgM
Term
Name the class of antibodies that are dimers.
Definition
IgA
Term
Hypervariable regions are also called ___________ regions.
Definition
complmentarity determining regions (CDR)
Term
What is a multivalent antigen?
Definition
when an antigen contains more than one epitope or more than one copy of an epitope
Term
What are chimeric monoclonal antibodies?
Definition
use a mouse V region with a human C region to create an antibody that only recognizes one epitope (monoclonal). Ex. Riftuximab--anti CD 20 (tx for non-Hodgin B cell lymphoma)
Term
What are humanized monoclonal antibodies?
Definition
when a mouse CDR is combined with a humna Ig to make an antibody specific to one epitope. Ex- Omalizumab used as antihuman IgE for allergies
Term
Adalimumab (an anti TNF alpha medication) is a _______ ________ antibody.
Definition
human monoclonal
Term
Which parts of the antibody are transcribed without gene rearrangment?
Definition
the leader peptide and the C region (the V region requires Gene rearrangment)
Term
What is somatic recombination?
Definition
When the V and J segments are cut and spliced by DNA recombination in "somatic" B cells.
Term
How is somatic recombination different in light chains than in heavy chains?
Definition
light chains require a single recombination (VL +JL) while heavy chains require 2 recombinations (D + JH = DJ + VH)
Term
In somatic recombination of heavy chains, what prevents V combining with J first instead of combining with D then J?
Definition
recombination signal sequences that flank segments
Term
What is the enzyme responsible for insertional diversity?
Definition
Terminal deoxynucleotidyltransferase (Tdt)
Term
RAG enzyme stands for _______.
Definition
Recombination acting genes
Term
What is junctional diversity?
Definition
When the variable segments (V, D or J) are joined together by nonhomologous end joining and the ends are modified and nucleotides are randomly added
Term
What are P nucleotides? What are N nucleotides?
Definition
P nucleotides are the palindromic nucleotides. The N nucleotides are the Non-templated nucleotides (nucleotides added by the enzyme terminal deoxynucleotidyl transferase)
Term
What is the function of RAG?
Definition
the associate with other enzymes to form V(D)J recombinase
Term
Is the isotype of an antibody determined by the heavy chain or the light chain?
Definition
the heavy chain
Term
How are both IgM and IgD antibodies with the same specificity made in naive B cells?
Definition
the VDJ region is before the IgM and the IgD region. After VDJ is transcribed, there is no strong stop signal so IgM and IgD exons are transcribed and attached to VDJ via alternative splicing
Term
Do naive B cells make more IgM or more IgD?
Definition
IgM
Term
The three types of diversity of antibodies that occur before cell encounters an antigen are...
Definition
combinatorial (combination of VDJ segments), Junctional (P nucleotides), Insertional (N nucleotides)
Term
What allows some IgM to be secreted and other IgM to be membrane bound?
Definition
different RNA processing of the antibody tail. MC tail is hydrophobic and transmembrane. SH tail is hydrophilic so membrane is secreted.
Term
What is the difference between affinity and avidity?
Definition
Affinity is the strength of binding at one site. Avidity is the overall strength of binding at multiple sites
Term
If IgM and IgA have the same affinity, will their avidity be the same?
Definition
No. IgM is pentameric so it has five binding sites and therefore will have a higher avidity
Term
Random, single mutations in the V region is termed ____.
Definition
somatic hypermutation
Term
Name the enzyme required for somatic hypermutation.
Definition
AID (activation-induced cytidine deaminase)
Term
Where on the antibody do somatic hypermutations preferentially occur?
Definition
in CDR loops
Term
What is affinity maturation?
Definition
When higher affinity antibodies are made as the infection progresses
Term
Why do we need different isotypes of antibodies?
Definition
because they serve different functions
Term
Which antibody isotype performs most functions?
Definition
IgG
Term
Which antibody isotype is responsible for sensitization of mast cells?
Definition
IgE
Term
What are switch sequences, or switch regions?
Definition
highly repetitive sequences flanking the 5 prime side of C genes
Term
How do B cells start making other isotypes of antibodies once they encounter an antigen?
Definition
The C genes for other antibodies are downstream from IgM and IgD. Before the different C genes (on the 5' end) are switch sequences or switch regions. AID joins together these switch regions and so the downstream antibody constant region is produced that can recognize the same antigen
Term
What enzyme is required for isotype switching?
Definition
AID (activation-induced cytidine deaminase) function= deaminate cytosines into uracils so uracil-DNA-glycosylase (UNG) can remove the uracil
Term
How many subclasses of IgG are there?
Definition
4
Term
Which antibody is the most abundant?
Definition
IgG
Term
Name the antibody isotype with no known purpose.
Definition
IgD
Term
How many sublcasses of IgA are there?
Definition
2
Term
What are the two possible phenotypes of hyper IgM syndrome?
Definition
1) susceptibility to pryogenic and opportunistic infections 2) susceptibility to pyrogenic infections
Term
Susceptibility to pyrogenic and opportunistic infections indicates defects in..
Definition
CD40 and CD40 ligand genes
Term
Susceptibility to pyrogenic infections indicates...
Definition
defect in AID gene
Term
How do B cells know when to "class switch" and go from making IgM to IgG?
Definition
cytokines released by T cells
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