Antibody molecules

Question 1

What are the basic 4 units of Igs?

Answer 1

• 2 identical heavy (H) chains each 50kDa
• 2 identical light (L) chains each 25kDa

Question 2

What domains of the Ig are glycosylates (carbohydrates attached to proteins)?

Answer 2

Ch2 (constant-heavy 2)

Question 3

What properties do each of the 12 Ig domains have?

Answer 3

• roughly 100AA long
• Each have an intra-chain S-S (disulphide) bridge.
• there are 2 sheets of beta strands

Question 4

What do the hypervariable regions of an antibody mean?

Answer 4

They have variable AAs. They form the antigen binding sequence. Hypervariable regions (HV) are aka complementarity-determining regions (CDR). there are 3 loops of HV on each H and L chain, and six CDR form the antigen binding sites.

Question 5

How many different C (constant) types are there and what do they do?

Answer 5

The constant regions control the effector function of the Ig.
IgM - mu (μ)
IgD - delta (δ)
IgG - gamma (γ)
IgE - epsilon (ε)
IgA - alpha (α)
MADGE
They’re produced at diff times and diff locations.

Question 6

What can the L chain of an Ig be? (one or the other)

Answer 6

kappa (κ) or lambda (λ) but they have no functional differences. The isotypic determinants are distinguished by the C regions.

Question 7

What does antibody valency mean?

Answer 7

This means the number of antigen binding sites.
Different isotypes have different valencies.
e.g. IgG is bi-valent (2 antigen binding sites)

Question 8

Tell me about IgM:

Answer 8

• when bound to a B cell as a receptor, it is known as a monomer (single unit). When the mature B cell starts secreting it, its secreted as a pentamer.
• therefore, IgM is excellent at agglutination as it is a large molecule with many binding sites (10)
• it captures lots of antibody, forming bigger mass, signalling our immune system at a bigger response.
  STRUCTURE
• mu x 2 and L x 2 of a molecular weight 180kDa, but timed by 5 so 900kDa.
• the 1st isotype to be produced
• relatively low affinity as it wants to capture anything nothing specific
• difficulty crossing membranes due to size so mainly found in blood
• valency of 10, therefore high avidity which means it has the ability to capture lots.
• activates complement

Question 9

Tell me about IgD:

Answer 9

• 2 delta constant chains weighing 185kDa
• long hinge
• often present alongside IgM on the B cell surface (BCR) during B cell maturation
• high concentration in serum with a largely unknown function and is not used very often

Question 10

Tell me about IgG:

Answer 10

• most prevalent in serum, specifically IgG1. As it activates the complement, ADCC, opsonisation AND it can cross the placenta walls! which can protect the foetus
• large increase in secondary immune response
• 2 gamma constant chains and 2 light chains
• it has four subclasses taht differ in their structures, functions, abundance and antigens they are to be produced for - the subclasses allow IgG to be more specific.

Question 11

What are the four subclasses of IgG?

Answer 11

IgG1 - looks like the basic IgG structure
IgG2 - slightly longer hinge region and the arms are closer together
IgG3 - very long hinge region allowing it to be the most flexible
IgG4 - very similar to IgG1

Question 12

Tell me about IgA:

Answer 12

• monomer in serum and a dimer in secretions and mucosa systems
• big role in protecting the gut and epithelial cells
• dimeric structure = there are 2 of them, joined to a J chain in the middle, facing each others Fc regions, means there is valency of 4
• there are 2 subclasses of IgA
• its function is to inhibit microbial adherence to mucosal surfaces, neutralise toxins and pathogens, prevent commensal bacteria from entering the blood stream and is present in early milk

Question 13

What are the 2 subclasses of IgA?

Answer 13

IgA1 - predominant in serum (monomer)
IgA2 - found in secretions (diamer)

Question 14

How does IgA access gut lumen?

Answer 14

The dimeric IgA is transported through epithelial cells at the base of the crypts into the gut lumen.
They will bind to the layer of mucus overlaying the gut epithelium.
They can then use their other side to bind pathogens and toxins before they get access to the mucous membrane.

Question 15

Tell me about IgE:

Answer 15

• MW of 200,000 and it has 5 domains instead of the usual 4 (extra pair in the constant region)
• it does not have a hinge region
• it has the lowest concentration in serum as it has very potent effects.
• has high affinity binding to FcR on mast cells and basophils and is important in ADCC.
• it has a role in allergies and asthma and induces eosinophils and basophils to release histamine and proteases

Question 16

Where are the Igs distributed in the body?

Answer 16

• IgG and IgM predominate the blood
• IgG and monomeric IgA predominate extracellular fluid
• Dimeric IgA in the GIT
• The brain is devoid of any Ig’s

Question 17

What does the Fc region do?

Answer 17

This is on the antibody, and it interacts with FcR (receptors) on other cells such as mast cells. mast cells contain basophils with histamine in them. mast cells surround blood and lymph vessels, and barriers to the outside such as the skin, mucosa of the GIT and lungs.

Question 18

What needs to occur in order for class switching?

Answer 18

Activation of a mature B cell via its membrane-bound antibody molecule (B cell receptor) - dependant on what antigen has bound to the BCR.

Question 19

How do IgE’s induce histamine expulsion from mast cells?

Answer 19

The IgE’s will bind Fc region to FcR on the mast cell. They will bind to antigens. Several IgE’s need to be bound to a mast cell before it can start releasing histamine. This prevents to much being released and attacking every ‘foreign’ cell. When cells release to much histamine, they cause asthma.