Lecture 6: B cells and antibodies

Question 1

What are antibodies?

Answer 1

Antibodies are Y-shaped antigen-specific proteins produced by B lymphocytes

Question 2

Describe the structure of antibodies

Answer 2

Antibodies are comprised of 2 identical heavy chains and 2 identical light chains.

Question 3

What leads to variation in antibodies?

Answer 3

Different heavy chain constant regions produce antibodies with different properties

Question 4

What do antibodies recognise?

Answer 4

Antibodies recognise ‘epitopes’ of an antigen through there variable antigen-binding site (FAB) on the heavy chain

Question 5

What is the role of the Fc region of antibodies?

Answer 5

The Fc region at the ‘stem’ of the antibody interacts with other cells and molecules of the immune system.

Question 6

Where are antibodies found?

Answer 6

Antibodies are attached to B cells at Fc region and are also secreted into the bloodstream and circulate as free proteins

Question 7

How many types of antibodies does each B cell produce?

Answer 7

Each B cell produces only 1 antibody; each antibody (and therefore each B cell) will be specific for particular protein antigens.

Question 8

What are the 5 antibody isotypes?

Answer 8

IgM, IgA, IgD, IgE, IgG

MADEG

Question 9

What is the role of IgM antibodies?

Answer 9

First antibody produced in an immune. Low affinity for antigen but produces pentamer to increase affinity.

Question 10

What is the role of IgA antibodies?

Answer 10

Only antibody that can cross mucosal surfaces and found in secretion. Protected from digestion by secretory component.

Question 11

What is the role of IgD antibodies?

Answer 11

Like IgM, the first antibody produced by a B cell, but has no known function.

Question 12

What is the role of IgE antibodies?

Answer 12

Circulates as a monomer; exact function not known, but believed to be important in parasitic infection and allergic disease.

Question 13

What is the role of IgG antibodies?

Answer 13

Main mature antibody form; circulates as a monomer.

Question 14

How does IgM differ as infection progresses?

Answer 14

As immune responses progress, the IgM response switches to other antibody isotypes.

Question 15

What are the 6 actions of antibodies?

Answer 15

1. Neutralisation
2. Receptor blocking
3. Opsonisation
4. Mast cell activation
5. Antibody-dependent cellular cytotoxicity (ADCC)
6. Complement activation

Question 16

How do antibodies trigger neutralisation?

Answer 16

Anti-toxin antibodies bind to the toxin and neutralise it.

Question 17

How do antibodies trigger receptor blocking?

Answer 17

Antibody blocks receptor used by organism to gain entry to host cell.

Question 18

How do antibodies trigger opsonisation?

Answer 18

Coat bacteria to allow for phagocytic cells to identify it and reduce repulsion between two negatively charged membranes. Phagocytic cells have receptors for the Fc portion of antibodies.

Question 19

How do antibodies trigger mast cell activation?

Answer 19

Mast cells have surface Fc receptors and become coated with IgE antibody from circulation. When antigen binds to the IgE antibodies and cross-links them, the mast cell ‘degranulates’, releasing histamine.

Question 20

How do antibodies trigger antigen-dependent cellular cytotoxicity (ADCC)?

Answer 20

NK cell recognises antibody-coated bacteria by Fc receptor; the target organism is then killed by non-phagocytic means.

Question 21

How do antibodies trigger complement activation?

Answer 21

Activates sequential proteolysis of proteins to generate enzyme complexes with proteolytic activity that trigger opsonisation, phagocytosis, inflammation and terminal attack pathway.

Question 22

How is IgE involved in allergy?

Answer 22

Inappropriate cross linking of normal proteins with IgE on mast cells causes unnecessary release of histamine.

Question 23

How is the variation in antibodies generated?

Answer 23

Somatic recombination of variable regions

Question 24

What are the advantages of somatic recombination of antibodies?

Answer 24

1. Huge diversity
2. large number of receptors from small area of DNA
3. Everybody has a unique repertoire

Question 25

What are the disadvantages of somatic recombination of antibodies?

Answer 25

1. Many combinations will not work out
2. B cells with dysfunctional receptors are destroyed and this is energy intensive
3. Deletion of B cells that can recognise self-antigens is not always efficient and so potential for autoimmune disease

Question 26

What is ‘clonal selection’ in B cells?

Answer 26

Clonal selection is the division and selection of the ‘fittest’ B cells. B cells receptors (antibodies) are generated at random, so presumably some will react to self-antigens, but they undergo selection to try and remove these.

Question 27

What is ‘affinity maturation’ in antibodies?

Answer 27

Affinity maturation is the strength of bonding between antibody and antigen

Question 28

What affects affinity maturation of antibodies?

Answer 28

1. Class switch

2. Somatic hypermutation

Question 29

What happens during class switching of antibodies?

Answer 29

IgM in the ‘primary response’ switches to IgG. The variable region of the antibody remains the same

Question 30

What happens during somatic hypermutation of antibodies?

Answer 30

Random mutations are introduced into the variable region of the antibody so produce a slightly different antibody. Clonal selection will determine the most beneficial mutations.

Question 31

How does subsequent exposure improve affinity maturation and the adaptive immune response?

Answer 31

Antibody response improves by affinity maturation so subsequent exposures to the same pathogen are characterised by high-affinity IgG antibodies in the secondary immune response.