Humoral immunity:B cell activation, affinity maturation and class switching Flashcards
How does lymphocytes development start in the bone marrow?
All lymphocytes starts off as haematopoietic stem cell which integrate into CMP : common myeloid progenitor, and CLP: common lymphoid progenitor.
What does CMP (common myeloid progenitor) differentiate into?
CMP differentiate into neutrophils, red blood cells and platelets.
What does common lymphoid progenitor differentiate into?
CLP differentiate into T cell precursors and B cell precursors.
When does the immunoglobulin gene rearrangement takes place?
It occurs between the differentiation of Pre-B to immature B cell (I’m-B)
What are secondary lymphoid organs?
Lymph nodes, spleen, peyers patches etc.
What are the two phase of humorist immune response?
Recognition and activation; which is proliferation as well as differentiation.
What happens in the recognition phase?
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.
What happens in the second phase: activation phase
The second phase kicks in with clonal expansion which produce four type of cells.
What are the four type of cells created during the second phase of hi oral immune response?
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
What are the stages development for antibody secreting cell?
Stem cell (HSC) -> pre B cell -> immature B cell -> mature B cell -> activated B cell -> antibody secreting B cell.
Which B cells produce which type of antibody?
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.
How does B cell do antigen maturation.
Matured B cell have membrane IgM which is that that allows antigen recognition which lead to B cell activation.
How does IgM work?
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.
What are the two forms of antibodies?
One is membrane bound as act as antigen receptor.
The other can be found in circulation, tissue and mucosa.
What happens when B cells get activated?
The activated B cell produce a large quantity of IgM and secreting it and later becomes a plasma cell
How does Ig know if the membrane bound or secreted
There are two alternative version of exon four; excretory or membrane bound. During splicing only one form will remain on the mRNA
What are the difference between membrane bound and secretory IgG?
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.
What does secreted IgGs do
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
How does antibodies work?
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.
How does antibodies neutralise toxins?
Antibodies bind to extra cellular microbes and toxins. They can neutralise it by either blocking its adherence to surfaces it block its entry.
During immune response B cell are capable of producing antibodies of different classes without changing specific antigen, what changes to what?
IgM can switch to IgG, IgE and IgA
IgG can switch to IgE and IgA
Does class switching involve the alteration of lift chain?
No so antigen complement remains the same
How does B cells produce different classes of Ig?
They have different constant regions.
What are the two mechanism to add C regions but remain the same VDJ region
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.