Humoral immunity: B cell activation, affinity maturation and class switching Flashcards
What do haematopoietic stem cells give rise to?
−common myeloid progenitor
−common lymphoid progenitor
What does the common myeloid progenitor give rise to?
all the blood cells eg neutrophils, red cells, platelets
What does the common lymphoid progenitor give rise to?
pre T and pre B cells
How does the pre B cell become a mature B cell?
pre B cell rearranges its immunoglobin gene
gives rise to immature B cell
after leaving bone marrow becomes mature B cell
Where do mature B cells sit?
secondary lymphoid organs (spleen, peyers patches, lymph nodes)
When the mature B cells sit in the secondary lymphoid organs, what receptors do they have on them?
IgM+ or IgD+
What is clonal expansion?
B cell encounters antigen when it gets signal from T helper cells
proliferation begins
What is the first type of cell produced when B cells proliferate?
plasma cells
What do plasma cells do?
plasma cells go back into the bone marrow antibody production (IgM)
What is class switching?
IgM might not be best antibody for the pathogen
B cell make diff antibody with same binding sites but different constant region of heavy chain
switches to IgG
When is IgA made instead of IgG in class switching?
if the infection is in the gut, or in mucus membranes, or in secretions, then the antibody made will be IgA
What is affinity maturation?
as immunity to the antigen is being developed, the antibodies get better
they have high affinity to the antigen and they get more effective
How does the type of immunoglobulin on and produced by B cells changes at different stages of its development?
pre B cell stage= cell makes Mu heavy chains
immature B cell stage= Mu heavy chain and lambda/kappa light chain making a membrane IgM receptor
mature B cell= IgM and IgD receptors
How does the B cell change class from IgM?
switches class by changing heavy chain constant region
What happens when B cell encounters an antigen?
- IgM is expressed on cell surface
- antigen binds to IgM on cell surface membrane
- activates tyrosine kinase
- transduction pathway
How do T cells help B cells?
- T cells tightly regulate B cells and antibody production
- antigen bind to IgM on B cell
- B cell engulf antigen
- phagolysosome
- antigen processed in small peptides
- peptides bind to MHC class II
- put on cell surface
- presented to T helper cells
- T helper cells bind to MHC class II on B cell surface
- Stimulates B cells
- cytokine release
What are the 2 forms of antibodies?
Membrane bound B cell
secretory antibodies
Why are plasma cells good to make antibodies?
rich in RER
rich in ribosomes
How can B cell change from membrane bound IgM to secreted IgM?
After activation, the B cell changes from membrane bound IgM to secreted IgM
heavy chain in IgM is a Mu heavy chain
the constant region of this Mu heavy chain has 4 exons (exons are regions of the DNA which codefor a protein)
the 4thexon in the Mu heavy chain gene has two alternative forms, translation of one form results in the production of a membrane bound protein, whilst translation of the other form leads to the production of a secreted protein
What are the functions of secreted antibodies?
neutralise microbes and toxins
opsonise microbes to enhance phagocytsis
complement system activated
What does the Fc region of an antibody do?
Fc region=the tail of the antibody=hangs outside the pathogen
signals to neutrophils to come phagocytose the pathogen
activated complement system
What part of the antibody activates the complement system?
Fc region
Where does IgG work best?
in blood
Where does IgM work best?
in blood
Where does IgA work best?
in the mucosa
doesnt activate complement system
What is IgE most effective against?
parasites
What happens in class switching?
during an immune response, B cells become capable of producing different types of antibodies from different classes without changing the specificity of the antibody (the antigen binding site remains the same, the constant region changes)
IgM can switch to IgG, IgA, and IgE
IgG can switch to IgA and IgE
What needs to be kept same in the antibodies during class switching?
specificity of the antibody= antigen binding site remains same, constant region changes
What is differential splicing (minor mechanism)?
IgG to IgD
- constant region for the heavy chain has two alternate forms, one is C-Mu, the other is C-Delta
−after transcription, the mRNA goes through splicing to remove introns
−initially, during splicing the C-Delta exon is removed to give rise to IgM (as C-Mu is translated into a protein)−alternatively, the C-Mu exon can be spliced and removed as well, giving rise to IgD−the VDJ region remains the same, thus only changing the constant region of the heavy chain
What is VDJ?
keep the antigen binding site the same which is coded by rearranged VDJ
What is the major mechanism?
going from IgG to all other classes
it is called DNA rearrangement
What happens in DNA rearrangement?
after getting signals from T helpercells to switch classes
endonuclease enzymes cut the DNA after the VDJ complex and before the heavy chain constant region
this results in removal of the C-Mu from the DNA, leaving the VDJ complex along with another constant region for the heavy chain transcription, splicing and translation now take place resulting in class switching
What happens when T cells bind to MHC II molecules on B cells?
CD40 ligand on T cells binds to CD40 on B cells
leads to cytokine production by T cell
What are the different cytokines T cells produce and what do they do?
if IFN gamma is produced, the B cell switches classes to producing IgG1, or IgG3
if IL-4 is produced, the B cell switches classes to IgE
if TGF beta and other cytokines are produced, the B cell switches to IgA
What is affinity maturation?
change in affinity
antibodies made in early immune response have lower affinity for antigen
later in response have higher affinity antibodies
Why is there a change in affinity of antiboides during the immune response?
somatic mutation
What does a B cell become?
o Plasma cells and start secreting great amounts of immunoglobulin (most migrate to bone marrow)
o Memory B cells
o Some will change the class of Ig they make (class switching)
o Some B cells that are very effective will get better! (affinity maturation)
What 3 things prevent autoimmunity in a B cell?
- Antigen binding to the B cell (sIgM), resulting in signal transduction pathways
- Co-stimulation by T cells
- Co-stimulation by cytokines
