Antibody Structure and Function

What are antibodies (immunoglobulins)? What are they on the surface of? What are they secreted by?

They are glycoproteins (proteins that are glycosylated) on the surface of naive B cells and are secreted by plasma cells

Where are antibodies present?

In the blood serum and secreted fluids such as saliva and milk

What are the four functions of antibodies?

1. Activate the classical complement pathway (activate MAC)

2. Act as opsonins to enhance phagocytosis

3. Neutralize toxins and viruses

4. Function as antigen receptors for B cells

What do phagocytes have?

Receptors for the tail portion of the antibody (Fc portion) called Fc receptors

Why is it good for antibodies to attach to the pathogen right away?

This is to make sure that the pathogen can’t attach to any other cell that it wants to infect

What do membrane-bound immunoglobulin molecules have (mlg)?

They have very short cytoplasmic tails and so they are not able to interact with intracellular signalling molecules

What does the antigen-binding receptor on B cells consist of?

1. mIg

2. Disulfide linked Ig-a/Ig-B heterodimer

What do the cytoplasmic tails of both Ig-a and Ig-B interact with?

Intracellular signalling molecules such as tyrosine kinases

Why is mIg associated with Ig-B and Ig-a heterodimer?

This is due to their short tails as they are not conducive to signalling, therefore, they associate with other proteins such as Ig-B and Ig-a to allow for intracellular signalling to occur

What happens when mIg meets its cognate antigen?

The variable region will bind and induce a structural conformation change. It is then able to signal through the recruitment and activation of kinases. Stimulated B cell gives rise to antibody secreting plasma cells through the help of T cells (not needed all the time)

What are the five isotopes of antibodies?

1. IgA

2. IgD

3. IgE

4. IgG

5. IgM

What are the monomers of the five isotopes of antibodies composed of? What are they held together by? Describe the structure

1. 2 identical heavy chains

2. 2 identical light chains

Held together by disulfide bonds and non-covalent interactions. It is a heterotetramer and is a symmetrical structure

What are the five classes associated with the heavy chains?

1. Alpha

2. Gamma

3. Mu

4. Epsilon

5. Delta

What are the 2 designated classes associated with the light chains? Do we specifically denote between the two?

1. Lambda

2. Kappa

No we don’t. Just say it can either be lambda or kappa

How many amino acids form the globular domains? What are they formed by?

110 amino acids and are formed by intrachain disulfide bonds

What is the variable region of heavy and light chains characterized by?

A variable amino acid sequence

What is the constant region of the heavy and light chains characterized by?

A relatively constant amino acid sequence

What does glycosylation affect?

Antibody stability and its interactions with other proteins

What region binds to the antigen? What type of antigen is it usually?

The variable region and it is usually a protein antigen

What is the constant region?

It is the tail and is the same within the isotope of the species

Is the number of disulfide bonds dependent on the isotope? Is the hinge region flexible?

Yes to both

What end of the antibody is the carboxy end? Amino end?

The bottom (tail portion)(carboxy) and the top of the light chain (amino end)

What portion of the antibody gives it effector activity? What is effector activity?

The tail portion and it is the ability to interact with other cells that have Fc receptors

What does the light chains contain?

One variable (1 VL) and one constant domain (1 CL)

What do the heavy chains contain?

One variable domain (1 VH) and 3-4 constant domains (CH 1-4)

What forms the antigen-binding site?

Variable region domains at the amino-terminal portion of heavy and light chains

How many hypervariable regions within the V region? What else are they called? What do they show?

3 and they are called CDR1-3. They show even greater amino acid sequence variability and form the antigen binding site

Where are framework regions? What do they show?

They are outside the hyper variable regions and exhibit much less amino acid variability

What do the hypervariable regions of antibody V domains lie in?

Discrete loops at one of the domain structures

What does the antigen bind to?

The hyper variable region

What is the hinge region composed of? Where does it form between? In what isotopes does it form?

Proline rich amino acid sequences between Ch1 and CH2 domains form a flexible hinge region. It forms in IgA, IgD, and IgG

What antibodies have no hinge regions? How many constant domains do they have?

IgM and IgE. They have four constant domains

Why is it good that antibodies have a hinge region?

This is because you don’t know the conformation of the antigen that the antibody will interact with. The epitope could be anywhere