Adaptive Immunity - immunoglobulin proteins and genes

Question 1

Describe and understand the function of different immunoglobulin components

Answer 1

Ig - antibody - large glycoproteins that recognize a specific Ag. Two different types:
1) membrane bound - B cell receptor (BCR)
2) non membrane bound (free floating) - antibody (Ab). Each Ig has a heavy chain (think of the base) and a light chain (linked to heavy chain). They are linked together with disulfide bonds.
There is a variable region( recognized antigens)and a constant region to both types of chain.
Usually a B cell can only produce one kind of heavy chain and light chain
The only except is right after a B cell matures, it will produce IgD and IgM until it finds an Ag
The very tips of the Y portion of the Ig are known as hypervariable regions
- these 5-7 long amino acid parts account for the enormous antigenic diversity associated with Ig molecules
Constant region - many in heavy chain portion, one in light chain. It contains differences. This is what gives rise to the different isotypes.

Question 2

What are the different immunoglobulin isotypes and forms?

Answer 2

Light chain isotypes (only in constant region) - contributes to diversity NOT function
- kappa (x)
- Lambda (upside down y)
Heavy Chain isotypes - G and A have subclasses
MEGA D
Mu - IgM, Delta, Gamma with subclasses IgG1, IgG2, etc, epsilon, and alpha with subclass IgA1, IgA2, etc

Question 3

What is isotype of class switching?

Answer 3

Heavy chains. This involves B cells. When a new B cell first matures, it will express two types of B cell receptors (IgM and IgD). After its first encounter with an Ag, it will ALWAYS produce IgM. IF the B cell then gets certain signals, the constant heavy chain region will undergo rearrangement which can lead to class switching. This happens because some antibodies are better at fighting off certain pathogens .

Question 4

What are structural isoforms?

Answer 4

the main difference between the membrane bound B cell receptor (BCR) and the free floating receptor antibody (Ab) is the very end domain on the heavy chain (tailpiece) - membrane bound has transmembrane domain to help keep it attached to a membrane while the secreted form doesn’t have transmembrane or cytoplasmic domains because it’s free floating. The secretory form of Ig has a secretary portion on it (found in mucus, tears and saliva)

• membrane bound (mIg) - plasma membrane (also called BCR)
• secreted (sIg) - found in blood (end domain is the tailpiece )
• secretory (Sig) - found in tears and saliva

Question 5

What are polymeric Immunoglobulins?

Answer 5

are multiple Ig’s linked together. IgM (5 linked together) and IgA (2 linked ) are the most common - both held together by J chains. this is how we get secretory Its - two linked IgA’s will become in contact with a special polymeric Ig receptor on an epithelial cell. It is then endocytosed into the cell and the special Ig receptor is cleaved from the epithelial cell and integrated into the two linked IgA’s. It is now a secretory Ig.

Question 6

What is V(D)J recombination?

Answer 6

this involved the removal of introns by the variable region. Ig genes have variable regions made up of many small DNA fragments - gene segments
a) variable (V)
b) diversity (D) - light chain doesn’t have this because its small
c) joining (J)
so in every naive B cell, these sections jumble up and thats what causes the large antigenic diversity of Ig’s. It occurs in the variable region of both light and heavy chains .DOESN’t change isotype.

Question 7

What’s an epitope?

Answer 7

part of Ag that actually binds to the Ab. it binds to the CDR3 of Ig in the heavy chain

Question 8

What’s affinity?

Answer 8

strength of non- covalent association between one antigen-binding site and one antigenic epitope

Question 9

Whats avidity?

Answer 9

the overall strength of the bond between a multivalent Ab and multivalent Ag. We can have low affinity (dealing with one bond) but high avidity (when multiple variable regions are bound to one Ag in a polymeric Ig). So IgM will have a high avidity because it’s 5 Ab’s like together which have a total of 10 potential binding sites

Question 10

What’s cross reactivity?

Answer 10

b/c theres only so many possible combos of possible antigens on the outside of a bad cell, its possible that an Ag on a bad cell can be the same as a good cell. So when a B cells makes an Ab to mark the bad cell, it will also mark good cells. This is how we get hypersensitivity syndromes and autoimmune diseases.