Humoral immunity:B cell activation, affinity maturation and class switching

Question 1

How does lymphocytes development start in the bone marrow?

Answer 1

All lymphocytes starts off as haematopoietic stem cell which integrate into CMP : common myeloid progenitor, and CLP: common lymphoid progenitor.

Question 2

What does CMP (common myeloid progenitor) differentiate into?

Answer 2

CMP differentiate into neutrophils, red blood cells and platelets.

Question 3

What does common lymphoid progenitor differentiate into?

Answer 3

CLP differentiate into T cell precursors and B cell precursors.

Question 4

When does the immunoglobulin gene rearrangement takes place?

Answer 4

It occurs between the differentiation of Pre-B to immature B cell (I’m-B)

Question 5

What are secondary lymphoid organs?

Answer 5

Lymph nodes, spleen, peyers patches etc.

Question 6

What are the two phase of humorist immune response?

Answer 6

Recognition and activation; which is proliferation as well as differentiation.

Question 7

What happens in the recognition phase?

Answer 7

In recognition phase the resting B cell with IgM and IgD on its surface binds to antigen and with helper T cells and other stimulus B cell become activated.

Question 8

What happens in the second phase: activation phase

Answer 8

The second phase kicks in with clonal expansion which produce four type of cells.

Question 9

What are the four type of cells created during the second phase of hi oral immune response?

Answer 9

Plasma cell which secrete IgM

IgG expressing B cell which undergo isotype switching

High affinity Ig expressing B cell which differentiate into two cells.

 - affinity maturation which release high affinity IgG
 - memory B cell

Question 10

What are the stages development for antibody secreting cell?

Answer 10

Stem cell (HSC) -> pre B cell -> immature B cell -> mature B cell -> activated B cell -> antibody secreting B cell.

Question 11

Which B cells produce which type of antibody?

Answer 11

Stem cells does produce any Ig.

Pre B cells produce cytoplasmic miu heavy chain as well as pre B receptors.

Immature B cell produce membrane IgM

A mature B cell produce IgM and IgD

Activated B cell have low rate of Ig production and undergoes heavy chain isotype switching and affinity affinity maturation

Antibody secreting cell have high rate of Ig secretion and reduced membrane Ig secretion.

Question 12

How does B cell do antigen maturation.

Answer 12

Matured B cell have membrane IgM which is that that allows antigen recognition which lead to B cell activation.

Question 13

How does IgM work?

Answer 13

Surface IgM is the first functioning Ig expressed. They act as a B cell receptor, binding of an IgM activates the tyrosine kinases and their signal transducer pathway. Wth T cells and cytokines mature B cells gets activated.

Question 14

What are the two forms of antibodies?

Answer 14

One is membrane bound as act as antigen receptor.

The other can be found in circulation, tissue and mucosa.

Question 15

What happens when B cells get activated?

Answer 15

The activated B cell produce a large quantity of IgM and secreting it and later becomes a plasma cell

Question 16

How does Ig know if the membrane bound or secreted

Answer 16

There are two alternative version of exon four; excretory or membrane bound. During splicing only one form will remain on the mRNA

Question 17

What are the difference between membrane bound and secretory IgG?

Answer 17

Both have V regions, light gain, heavy chain and C regions

However on the heavy chain; secreted only have a tail piece where as membrane bound have an extra transmembrane region and cytoplasmic tail.

Question 18

What does secreted IgGs do

Answer 18

Secreted IgG circulate in blood and access various site to deal with pathogens.
It’s effector functions are:
-neutralisation of microbes such as toxins
-opsonisation of microbes to enhance phagocytosis
-Activation of complement

Question 19

How does antibodies work?

Answer 19

Different classes of antibodies work best at retain sites; IGM and IgG work best in blood, IgA work best in mucosa

Different classes of Antibodies also work best against certain pathogens such as IgE is best against parasites.

Question 20

How does antibodies neutralise toxins?

Answer 20

Antibodies bind to extra cellular microbes and toxins. They can neutralise it by either blocking its adherence to surfaces it block its entry.

Question 21

During immune response B cell are capable of producing antibodies of different classes without changing specific antigen, what changes to what?

Answer 21

IgM can switch to IgG, IgE and IgA

IgG can switch to IgE and IgA

Question 22

Does class switching involve the alteration of lift chain?

Answer 22

No so antigen complement remains the same

Question 23

How does B cells produce different classes of Ig?

Answer 23

They have different constant regions.

Question 24

What are the two mechanism to add C regions but remain the same VDJ region

Answer 24

First mechanism is known as minor which is in IgD only, this is done via differential splicing and it’s made at the same as IgM.

Second mechanism is known as major, this is for all the other classes via DNA rearrangement.

Question 25

There are endonuclease recognition before each C segment how is differential splicing different to DNA segment rearrangement?

Answer 25

Differential splicing is when two constant region is transcribed, differential splicing not remove one of the constant exon so the other is used.

Rearrangement is spliced many Constant regions.

Question 26

How does T helper cell wth antibody class switch?

Answer 26

There are two ways:

CD4OL (ligand) on T cell interacts with CD4O on B cell lead to class switch

Cytokines produced by T cells also lead to class switch, IFN gamma cause antibodies switch to IgG1 and IgG 3
IL-4 cause antibody to switch to IgE
TGF beta with other cytokines cause antibodies to switch to IgA.

Question 27

What is affinity maturation?

Answer 27

So antibodies produced during early phases of immune response have lower affinity for antigen. Later on in secondary immune response produces high affinity antibodies. This process is affinity maturation

Question 28

How is affinity maturation reached?

Answer 28

B cells with high affinity Antigen receptors are elected to survive, higher affinity gives stronger cell signalling which lead to faster cell replication and high affinity sub clone out grows the original clone. This involves somatic mutation in Ig V genes.

Affinity maturation also need signals from helper T cells