Antibody Structure and Function III

What is the class on the heavy chain for IgG? What is the number of CH Ig domains? How many subclasses? Light chain class? J chain?

Heavy chain class: Gamma

Number of CH Ig domains: 3

Subclasses: gamma1, gamma2, gamma3, gamma4

Light chain: Lambda or kappa

J chain: None

What is the class on the heavy chain for IgM? What is the number of CH Ig domains? How many subclasses? Light chain class? J chain?

Heavy chain class: Mu

Number of CH Ig domains: 4

Subclasses: None

Light chain: Lambda or kappa

J chain: Yes

What is the class on the heavy chain for IgA? What is the number of CH Ig domains? How many subclasses? Light chain class? J chain?

Heavy chain class: Alpha

Number of CH Ig domains: 3

Subclasses: alpha1, alpha2

Light chain: Lambda or kappa

J chain: Yes

What is the class on the heavy chain for IgE? What is the number of CH Ig domains? How many subclasses? Light chain class? J chain?

Heavy chain class: Epsilon

Number of CH Ig domains: 4

Subclasses: None

Light chain: Lambda or kappa

J chain: None

What is the class on the heavy chain for IgD? What is the number of CH Ig domains? How many subclasses? Light chain class? J chain?

Heavy chain class: Delta

Number of CH Ig domains: 3

Subclasses: None

Light chain: Lambda or kappa

J chain: None

What are joining chains for?

Mulimeric structures (antibodies that are not monomers)

Can IgM be a monomer and a pentamer? In what circumstances?

Yes and it is a monomer when it is on the cell and a pentamer when secreted

What is the structure of IgG?

1. 2 identical gamma heavy chains

2. 2 identical kappa or lambda light chains

How many IgG subclasses are there in humans? Why are there this many?

Four because they all have different function and biological properties but there is some overlap

What antibody is the most abundant in serum and extravascular spaces?

IgG

What is the function of IgG?

1. Neutralize viruses/toxins

2. Opsonizes microbes

3. Activates classical complement pathway

4. Mediates ADCC reactions

5. Crosses the placenta during pregnancy

What antibody can provide the baby with some sort of immunity before its immune cells start functioning?

IgG

What does the hinge region provide the antibody with?

A lot of flexibility for its functions. It allows it to bind to the epitope on an antigen with any conformation

What are the four types of movement that the IgG molecule can carry out?

1. Waving the Fab arms

2. Rotation of the Fab arms

3. Wagging the Fc tail

4. Bending the Fab elbow

Do all IgG subclasses have equal flexibility?

No they do not. Some have more disulfide bonds than others. The more disulfide bonds = more rigidity

Which IgG subclass has the greatest number of disulfide bonds and therefore is the least flexible?

IgG3

What IgG molecules are the most prevalent in your body?

IgG1 and IgG2

What does the hinge region make IgG molecules susceptible to? What is this reflected in?

Proteolytic cleavage. This is reflected in its half life

Which IgG molecule has the shortest half-life? What is it the best at?

IgG3 and is the best at activating complement

What is IgG2 good at responding to?

Carbohydrate antigens

Do all IgG molecules respond to protein antigens?

Yes they do

What does IgG4 respond to?

Allergies

What can IgG4 molecules do in the circulation?

They can switch their specifities and become functionally monovalent

Describe how IgG4 become functionally monovalent

1. Two different IgG4 molecules have two different specificities as shown in their hyper variable region (can bind to different antigens)

2. One IgG4 molecule can swap itself for another IgG4 molecule (have half of one and half of the other)

3. Now you have a monovalent antibody instead of a bivalent one

What is an advantage of having a monovalent antibody?

It allows that antibody to bind to two different epitopes instead of waiting around for the other antibody to come through the circulation to bind to the antigen (makes it more efficient)

Describe the structure of IgM

1. Expressed as a monomer on the surface of B cells

2. Secreted by plasma cells as a pentamer containing a J chain

3. 2 mu heavy chains

4. 2 kappa or lambda light chains

Out of the 10 antigen binding sites on pentameric IgM how many are able to physically interact with large antigens?

5

What is the first immunoglobulin class made by newborns and in a primary immune response?

IgM

What is the function of IgM? Is it as efficient as IgA?

1. Efficient agglutinates of particulate antigens

2. Activator of the classical complement pathway

No

Is the concentration low of high in fluid between cells of IgM? Why?

Low because it is challenging to get it across blood vessel walls

What allows the pentameric IgM to be transported across epithelial mucosa? What holds the five chains together?

J chain. Disulfide bonds

Describe the structure of IgA

1. Present as a monomer in serum

2. Dimer in mucosal secretions

3. 2 alpha heavy chains

4. 2 lambda or kappa light chains

What is the dimeric form of IgA formed in?

Plasma cells by the addition of a J chain

When is the secretory component of the IgA dimer added? What does it protect it from?

During its passage through glandular epithelial cells to protect secreted IgA molecules from proteolysis

What is the function of dimeric IgA?

It defends mucosal surfaces against microbial attacks by inhibiting pathogen adherence (pathogens can’t bind to the surface of the epithelium)

What are IgA-antigen complexes trapped in? How are they eliminated?

In mucus and by mechanical action

How does IgA provide newborns with mucosal immunity to environmental pathogens?

It is found in breast milk to perform this role

Describe how secretory IgA is formed

1. Plasma cell makes dimeric IgA through the help of T cells

2. Poly-Ig receptor on the submucosa region will become part of the secretory component of IgA by binding to the dimeric form

3. It becomes endocytose and there is enzymatic cleavage of the poly-Ig receptor at the base and conformational changes take place

4. It is now secreted to the outside into the lumen

What is the function of the secretory IgA?

It protects IgA from enzymatic cleavage