Adaptive Immunity: B-cell Response

Question 1

What are the functions of B cells?

Answer 1

1. Protect against infection by the production of antibodies
2. Presentation antigen to CD4 T cells through class II MHC
3. Regulation by the production of cytokines: B cell derived cytokines are predominantly IL-10 and TNFa (tumoir necrosis factor) (IL-10 producing suppressive B cells are known as Breg cells)

Question 2

What does a B cell receptor comprise?

Answer 2

An antibody molecule of 2 identical heavy chains & 2 identical light chains.
The antibody molecule has a transmembrane domain but no independent signalling capability.

B cell receptor signalling is dependent on Ig alpha and Ig beta

Question 3

What does an antibody look like?

Answer 3

The heavy chains are joined together by disulphide bonds identified by the dotted oval
The light chains are joined to the heavy chains by disulphide bonds identified by dotted circles
The ovals that are joined together to form the heavy and light chains structures are called domains

Question 4

What is B cell receptor signalling dependent on?

Answer 4

Ig-alpha & Ig-beta (aka CD79a and b)

Question 5

What do antibodies recognise on the surface of pathogens?

Answer 5

Epitopes

Question 6

What do the antibodies do when they recognise the epitopes on the surface?

Answer 6

Binding occurs via the tips of the Y shapes that are highly variable between B cells.

Question 7

What are the hinge, Fab & Fc portions of an antibody?

Answer 7

look at slide 6

The hinge is what allows the antibody to bend & some have a longer hinge allowing them to bend more.
The part of the antibody above the hinge is sometimes referred to as the Fab

The part of the antibody comprising the hinge and below is sometimes referred to as the Fc & some cells, including macrophages and neutrophils, have receptors for antibody that bind the Fc (Fc receptors).

Question 8

What is the term Fc often followed by?

Answer 8

The Greek letter for the class of antibody that the Fc receptor recognises.

Question 9

What are the 5 different immunoglobulin ‘isotypes’ or ‘classes’?

Answer 9

IgG, IgM, IgD, IgA & IgE

Question 10

What are the 4 subclasses of IgG in humans?

Answer 10

IgG1, IgG2, IgG3, IgG4, numbered by their abundance in human blood so IgG1 is the most abundant subclass.

Question 11

Which other Ig isotype has subclasses?

Answer 11

IgA in humans has 2 subclasses that differ in their constant region sequences that are encoded by different gene segments

Question 12

Which IgA is found in blood?

Answer 12

IgA in blood is mostly IgA1 whereas IgA in gut can be either IgA1 or IgA2.

Question 13

What property does IgA & IgM have?

Answer 13

They can be polymeric.

IgM in blood is pentomeric. It comprises 5
units of IgM held together by a molecule
called J chain. ‘J’ stands for ‘joining’.

IgA can be monomeric of dimeric. When
IgA is dimeric the two units are also held
together by J chain.

IgA1 and IgA2 subclasses can each be
dimeric or monomeric. Therefore there
are 4 different types of IgA.

Question 14

What is blocking?

Answer 14

Blocking is a function of antibodies. Blocking is when the antibodies bind to a target to prevent it binding to a receptor.

look at slide 8: An example is blocking toxin from binding to toxin receptor.
Another example is blocking a virus preventing it
from binding to its receptor

Question 15

What is complement fixation?

Answer 15

look ar slide 9: This is another function of antibodies is to IgG and IgM can ‘fix’ complement when they bind to a surface.
This initiates the complement cascade that results in the production of proinflammatory molecules and formation of the membrane attack complex.

Question 16

What is opsonisation by antibodies?

Answer 16

Bacterium is coated with complement & IgG antibody & when C3B binds to Cr1
Bound IgG can be recognised by Fc receptors of phagocytes, which facilitates phagocytosis
The antibody can be referred to as an opsonin & the antibody coated target is said to be opsonised
Complement C3b can also be opsonin.

Question 17

What is ADCC?

Answer 17

Antibody-dependent cellular cytotoxicity
Antibody binds antigens on the surfaces of target cells & an IgG antibody bound to a target cell can be recognised by natural killer (NK) cells via their Fc-gamma receptors
The NK cells with cross-linked Fc receptors can secrete cytotoxic granules into the synapse, resulting in the death of the target cell via apoptosis.

Question 18

What is agglutination?

Answer 18

Polymeric antibodies with multiple binding arms can cross link pathogen resulting in formation of a lattice
This can ‘disarm’ the pathogen.

Question 19

Which immunoglobulin isotype is especially good at agglutination and give an example?

Answer 19

IgA- polyclonal IgA antibodies can be actively secreted at mucosal sites such as the gut, eyes and mouth and are at relatively high concentration in mucus, saliva and tears compared to other antibodies.

Question 20

What does IgA, therefore, have a specific role in?

Answer 20

Regulating microbial populations due at least in part to its ability to coat and agglutinate bacteria

Question 21

What is mast cell degranulation?

Answer 21

Exocytosis of granules from mast cells with release of mediators of inflammation and bronchoconstriction

Question 22

How does mast cell degranulation occur?

Answer 22

Mast cells contain granules each containing proinflammatory molecules including histamine.

Mast cells have receptors for IgE (Fce receptors).
IgE can bind to the Fce receptors of mast cells and so long as the IgE is not cross linked, there will be no consequences.

If the IgE bound to the Fce receptors of mast cells becomes cross linked, the mast cell will become activated and granules released resulting in a characteristic ‘allergic’ reaction.

Question 23

what are the functions of antibodies?

Answer 23

1. Blocking
2. Complement fixation
3. Opposinisation
4. ADCC
5. Agglutination
6. Mast cell degranulation o

Question 24

What is the antibody variable region & what does it comprise?

Answer 24

The tip of the antibody Y-shape is the variable region
The variable region of the heavy chain is comprised of 3 segments called Variable (V), Diversity (D) and Joining (J).

Question 25

Where are the three segments that comprise each variable region assembled from?

Answer 25

From multiple alternatives during B cell development

Question 26

What is the difference between T-dependent & T-independent B cell responses?

Answer 26

T-dependent B-cell responses require the antigen to have a protein component
T-independent B-cell responses depend on antigens having repeat subunit structures so that they can cross-link the B cell receptor

Question 27

What sequence of events result in affinity maturation of B cells?

Answer 27

Centroblasts (at the germinal centre) divide rapidly and undergo somatic hypermutation of antibody variable region genes. They have no antibodies on their cell surface.

Centroblasts mature into relatively non dividing centrocytes and re-express antibody.

Centrocytes will sample antigen stored by STROMAL cells called follicular dendritic cells IF their antibody has sufficient affinity.

Centrocytes able to sample antigen, process and present it to T follicular helper cells and acquire help to survive.

Centrocytes with low affinity antibody cannot compete for antigen do not receive a T cell survival signal and die.

A Darwinian process of survival of the fittest.

Affinity maturation

Question 28

What does the germinal centre response generate?

Answer 28

Memory cells & plasma cells

Memory B cells can reside in tissues and circulate in blood. Can be IgM+ or class switched. Have antibody variable regions genes that are mutated by somatic hypermutation.

Plasma cells home to bone marrow or gut. Can be IgM+ or class switched. Have antibody variable regions genes that are mutated by somatic hypermutation.