Lecture 13: B cells and antibodies

Question 1

Where do T cells develop and where do B cells develop?

Answer 1

T cells develop in the thymus, whilst B cells develop in the bone marrow

Question 2

What are both B cells and T cells derived from?

Answer 2

Both B & T cells are derived from common lymphoid progenitor cells, which are themselves derived from haemopoietic stem cells originating in the liver (foetuses) or bone marrow (adults)

Question 3

Is it true that unlike T cells, B cells recognise their antigens as soluble proteins?

Answer 3

Yes

Question 4

How do B cells recognise their antigens as soluble proteins?

Answer 4

① Soluble antigens in blood or lymph.

② BCR 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 5

What do activated B cells differentiate into?

Answer 5

Activated B cells differentiate into Ab- secreting effectors/plasma cell

Question 6

What is the difference between a Resting B cell and a plasma/effector cell?

Answer 6

Plasma cell is increased in volume and ER size to allow for the excretion of ~ 5000 antibodies per second

Question 7

Describe the basic structure of an antibody

Answer 7

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 9

If an antibody has two identical antigenic determinants, what can happen?

Answer 9

If an antigen has two identical antigenic determinants, antibodies can CROSS-LINK the antigens, making small cyclic complexes or linear complexes

Question 10

What happens if an antibody has 3 or more identical antigenic determinants?

Answer 10

With more antigenic determinants expressed on antigens, antibody cross-linking can generate large 3-dimensional lattices

Question 11

What happens if an antibody has 3 or more different antigenic determinants?

Answer 11

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

Question 13

what is the collective name for all the different classes of antibodies?

Answer 13

The collective name for antibodies is Immunoglobulin (Ig).

Question 14

How many classes of antibodies do mammals usually make?

Answer 14

Mammals (usually) make 5 classes of Ig, distinguished by their H chains:

Question 15

What is used to distinguish between the differnt classes of antibodies?

Answer 15

The H (heavy) chain

Question 16

What are the different classes of antibodies? Describe their H chains as well

Answer 16

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

Question 17

Which mammals make unusual antibodies?

Answer 17

Camels

Question 18

What is unusal about the anibodies of camels?

Answer 18

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

Question 19

What fish makes unusual antibodies?

Answer 19

Sharks

Question 20

What is unusual about the antibodies of sharks?

Answer 20

Sharks make some H chain antibodies that cannot accept a L chain.

They also make IgM antibodies.

Question 21

Do invertebrates make antibodies?

Answer 21

No

Question 22

What is the most primitive antibody?

Answer 22

IgM

Question 23

Describe IgM

Answer 23

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

Cross links antigens together very efficiently , as can bind 10 antigens

These are the first antibodies that a B cell makes: over time, many B cells will ‘switch’ to making other Ig molecules, but these new antibody forms will RETAIN the SAME SPECIFICITY as the original IgM.

In a pre-B cell in the bone marrow, IgM are membrane-bound and form B cell receptors

Question 24

IgM and IgD are both BCRs: but IgM can be secreted

Answer 24

IgM and IgD are both BCRs: but IgM can be secreted

Question 25

Immature naïve B cell in bone marrow expresses surface IgM as its receptor This then migrates into the lymphoid tissue B cell now starts to also express membrane-bound IgD. This is a developmental marker of a more mature B cell. Once the B cell has both IgM and IgD present on its cell membranes, it can now repsond to soluble antigens. This is helped by t helper cells, which aid clonal expansion and differntiation of the b cells into plasma cells. The plasma cells will now secrete IgM and can release the antibodies

Question 26

First initial response is IgM being secreted

Answer 26

First initial response is IgM being secreted

Question 27

When can B cell respond to soluble antigens?

Answer 27

When it has both IgM and IgD on its cell surface membrane

Question 28

When is IgM secreted from plasma cells?

Answer 28

After clonal expansion

Question 29

Is it true that igM can trigger the complement pathway? (C1, cleaves C2 etc)

Answer 29

Yes, the classical pathway though. tail regions at the bottom of IgM stimulates the complement pathway.

Question 30

How efficient is IgM at activating complement?

Answer 30

Very efficient

Question 31

Why can't phagocytic cells recognise pathogens/antigens cross-linked or coated with IgM?

Answer 31

Because Phagocytic cells do not have a receptor for IgM. Thus IgM acting alone is ineffective in assisting phagocytosis.

Question 32

Why is IgM considered as an opsonin?

Answer 32

IgM is extremely efficient at activating complement An opsonin is any molecule that targets antigens for phagocytosis: complement is also an opsonin. Coating of a target with IgM (or other antibodies) or complement is a process called OPSONISATION

Question 33

IgM molecules of the humoural arm of the adaptive system interact with innate immune systems, directing complement for direct killing, or marking antigens with complement for phagocytosis.

Answer 33

IgM molecules of the humoural arm of the adaptive system interact with innate immune systems, directing complement for direct killing, or marking antigens with complement for phagocytosis.

Question 34

Is it true that IgM secreting plasma cells can switch to IgG secretion?

Answer 34

Yes

Question 35

Describe IgG

Answer 35

IgG has the standard tetrameric structure: 2 H chain (γ) and 2 L chains. After switching, the IgG has the SAME binding specificity as the IgM. It is very abundant, being 70-75% of the immunoglobulin in human serum. There are four subclasses, IgG1-4.

Question 36

What are the functions of IgG?

Answer 36

- toxin neutralisation; - binding to micro-organisms and opsonisation by coating a pathogen and by activating complement, thus leading to phagocytosis; - and provision of passive immunity to foetuses and newborns.

Question 37

Is it true that some IgG subclasses can cross the placenta and provide passive immunity?

Answer 37

Yes

Question 38

How do some IgG subclasses cross the placenta and provide passive immunity?

Answer 38

Placental cells take up maternal IgG by pinocytosis. Placental endosomes have receptors (FcRn receptors) that recognise and bind the tail region (Fc) of IgG antibodies. The IgG molecules are transported across the placental cells in vesicle carriers (transcytosis). Ig is released into the foetal circulation.

Question 39

Which igG subclass crosses the placenta poorly?

Answer 39

IgG2 crosses the placenta poorly.

Question 40

How is IgG secreted into mother's milk?

Answer 40

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). Ig is released into the neonatal circulation.

Question 41

How does igG act as an opsonin?

Answer 41

IgG can bind and coat pathogens. Phagocytic cells have receptors (Fc receptors) that recognise and bind the tail region (Fc) of the bound IgG antibodies. The result is stimulation of phagocytosis

Question 42

Is it true that igM-secreting plasma cells can switch to IgA secretion?

Answer 42

Yes

Question 43

Describe IgA

Answer 43

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. After switching, the IgA has the SAME binding specificity as the IgM. IgA protects our mucosal surfaces: and provides some passive immunity to newborns via milk

Question 44

Is it true that IgM-secreting plasma cells can switch to IgE secretion?

Answer 44

Yes

Question 45

IgE..

Answer 45

- IgE has the standard tetrameric structure (2H, 2L chains) After switching, the IgE has the SAME binding specificity as the IgM. IgE binds Fc receptors on: Mast cells (in tissues) and Basophils (in blood) and eosinophils The bound IgE then act as (passively acquired) receptors for the particular antigens to which the original clonal expansion took place.

Question 46

What does IgE trigger?

Answer 46

IgE triggers mast cell/basophil degranulation The result is release of histamine at the site where mast cells and basophils meet pathogen/antigen. Histamines trigger blood vessel dilation and inflammation: the vessels become leaky, allowing entry of white blood cells antibodies and complement to the site of mast cell /basophil activation. Uncontrolled IgE reactions : hay fever, asthma

Question 47

Does IgE also act as a receptor for eosinophils and how?

Answer 47

Yes Eosinophils attacking a schistosome larva: it’s too big … … but 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. Thus the IgE-specific Fc receptors on mast cells, basophils and eosinophils allow these cells to be targeted to different antigens/pathogens. The antibody arm of the adaptive immune system can direct parts of the innate immune system, as and when required.