Lecture 13. B Cells and Antibodies

Question 1

Where do B cells develop?

Answer 1

Bone marrow

Question 2

How do B cells recognise their antigens?

Answer 2

As soluble proteins

Question 3

Process of B cells binding to antigens

Answer 3

1. Soluble antigens in blood or lymph
2. BCR (B cell receptor) recognises ‘self’ antigen: no action taken
3. BCR recognises no antigen: no action taken
4. BCR recognises ‘non-self’ antigen: activation, mitosis and clonal expansion of specific B cells

Question 4

What is the structure of a resting B cell?

Answer 4

Has membrane-bound antibodies that constitute the B cell receptor

Question 5

What is the structure of an effector B cell?

Answer 5

Massive increase in ER allows secretion of ~5000 antibodies per second

Question 6

What is the basic structure of an antibody?

Answer 6

Tetrameric, with four polypeptide chains – 2 identical heavy chains (H) and two identical light chains (L), held together by covalent disulfide bonds at the hinge and between H and L chains

Question 7

What can one antibody tetramer bind to?

Answer 7

Two identical antigens

Question 8

What can antibodies do if an antigen has two identical antigenic determinants?

Answer 8

Can cross-link the antigens, making small cyclic complexes or linear complexes

Question 9

What can antibodies do if an antigen has three identical antigenic determinants?

Answer 9

Antibody cross-linking can generate large 3-dimensional lattices

Question 10

What can antibodies do if an antigen has three or more different antigenic determinants?

Answer 10

If multiple antigenic determinants are available, antibodies with different specificity can co-operate

Question 11

Why is cross-linkage important for phagocytes?

Answer 11

These large networks make it easier for phagocytes to engulf pathogens or soluble antigens, which can then be degraded and re-presented to T cells, amplifying the immune response

Question 12

What is the collective name for antibodies?

Answer 12

Immunoglobulin (Ig)

Question 13

What are the 5 classes of immunoglobulin?

Answer 13

IgM - μ heavy chain
IgD - δ heavy chain
IgG - γ heavy chain
IgA - α heavy chain
IgE - ε heavy chain

Question 14

What distinguishes the 5 classes of immunoglobulin?

Answer 14

H chains

Question 15

What is unusual about antibodies produced by camels?

Answer 15

About 50% of their antibodies have H chains that cannot take a L chain partner

Question 16

What is unusual about antibodies produced by sharks?

Answer 16

Sharks make some H chain antibodies that cannot accept a L chain
They also make IgM antibodies

Question 17

Do invertebrates make antibodies?

Answer 17

No

Question 18

Which Ig is the most primitive?

Answer 18

IgM

Question 19

What is the structure of IgM?

Answer 19

A pentamer of the basic tetrameric unit, held together by a J (joining) chain thought to aid polymerisation of the complex

Question 20

What are the first antibodies B cells make?

Answer 20

IgM

Question 21

What does bound IgM trigger?

Answer 21

‘Classical‘ pathway via their tail regions
Can activate complement proteins

Question 22

Why is IgM considered an opsonin?

Answer 22

IgM is extremely efficient at activating complement

Question 23

What is an opsonin?

Answer 23

Any molecule that targets antigens for phagocytosis

Question 24

What is the structure of IgG?

Answer 24

IgG has the standard tetrameric structure: 2 H chains (γ) and 2 L chains

Question 25

How abundant is IgG?

Answer 25

Very abundant, being 70-75% of the immunoglobulin in human serum

Question 26

How many subclasses of IgG are there?

Answer 26

4: IgG1-4

Question 27

What are the functions of IgG?

Answer 27

Toxin neutralisation
Binding to micro-organisms and opsonisation by coating a pathogen and by activating complement, thus leading to phagocytosis
Provision of passive immunity to foetuses and newborns

Question 28

How do placental cells take up maternal IgG?

Answer 28

By pinocytosis
Placental endosomes have receptors (FcRn receptors) that recognise and bind the tail region (Fc) of IgG endosome antibodies
The IgG molecules are transported FcRn across the placental cells in vesicle Fc carriers (transcytosis)

Question 29

Which subclass of IgG crosses the placenta poorly?

Answer 29

IgG2

Question 30

How does IgG secreted in maternal milk provide passive immunity?

Answer 30

FcRn receptors on neonatal gut cells (enterocytes) recognise and bind the tail region (Fc) of IgG antibodies
The IgG molecules are transported across the enterocytes in vesicle carriers (transcytosis)

Question 31

What is the structure of IgA?

Answer 31

IgA is a dimer of two tetrameric structures held together by a J chain, and also an S chain (secretory component), which allows secretion into saliva, tears, milk and mucus

Question 32

What does IgM share with IgG, IgA and IgE?

Answer 32

The same binding specificity

Question 33

What is the function of IgA?

Answer 33

IgA protects our mucosal surfaces: and provides some passive immunity to newborns via milk

Question 34

What is the structure of IgE?

Answer 34

IgE has the standard tetrameric structure (2H, 2L chains)

Question 35

What does IgE bind to?

Answer 35

Fc receptors on mast cells (in tissues), basophils (in blood) and eosinophils

Question 36

What does IgE trigger?

Answer 36

Cell/basophil degranulation resulting in the release of histamines where the mast cells and basophils meet the pathogen/antigen

Question 37

What does uncontrolled IgE reactions lead to?

Answer 37

Hay fever and asthma

Question 38

How can eosinophils kill schistosome larva?

Answer 38

If the larva is opsonised (coated) with complement or if the eosinophils use IgE as a passively required receptor, eosinophils can recognise and collectively kill it