B lymphocytes Flashcards
What can B cells be used for?
major vaccine targets, as induce antibody responses; monoclonal antibodies are exploited for cancer, asthma, pregnancy testing and viral infection
What are B lymphocytes?
They are WBCs that are derived from haemotopoetic stem cells.
Effector cells or humoral immunity- secrete antibodies and they have memory B cells (prevents repeat infections)
Where do B lymphocytes come from?
Derived from stem cells in the bone marrow
The migrate into the circulation and into lymphoid tissues.
Mature B cells are specific for one antigen- specifity resides in the B cell receptor (BCR) antigen- it is membrane anchored antibody
What is the difference between T cells and B cells?
The main difference is the type of epitope that they recognise.
T cells recognise linear epitopes (in the context of MHC)- they identify the sequence
B cells- identify the structure
What happens when the t helper cells bind to the antigen on BCR?
T cells secrete lymphokines after recognition of the antigenic self on the B cell.
B cell will enter cell cycle and develop into a clone of cells with identical BCRs
What are the three core roles of antibodies?
- Neutralisation
- Osponisation
- Complement activation
There are 5 classes of antibodies: A,D,E,G and M
Describe the thymus independent activation.
Directly activate B cells without help of T-Cells, often bacterial polysaccharides with repetitive structure (subunits) and second signal required provided by microbial constituent - from PAMPs
What are some problems with B cells?
autoimmunity, allergy (anaphylaxis) and can become cancerous (lymphomas and myelomas) under the influence of viruses.
What is clonal selection?
Interaction between a forgein molecule and that receptor leads to activation. Differentiated effector cells of that lineage will bear the same receptor.
Self-specific receptors are deleted early in development.
There are two types of adaptive response- what are they?
- Humoral (B cells) and antibodies- they are soluble
- Cell-mediated- T cells, cytokines and killing :)
What is somatic hypermutation and affinity maturation?
This refers to the improvement in the immune system between the primary and secondary response.
Mutation of VDJ block (antigen recognition)
VDJ block of antigen recognition slightly mutates due to AID (activation-induced deamination) which induces point mutations, changing cytosine in GC to an A so you get a T on the opposite strand- these small point mutations cause changes to the antibody structure.
There are small changes in the B cell- it is an evolutionary process.
How are the immunoglobin heavy chains formed?
gene rearrangement similar to light chains but
light chain= v+J
heavy chains= v+d+J
Start off with germline DNA- the different areas reshuffle and rearrange by recombination using vdj recombinase. A few V,J and D regions are passed down- the constant region is what determines the type of antibody- e.g. alpha constant region gives rise to IgA.
there is also variation in splicing
How are the V and J regions cut out randomly?
V(D)J recombinase is an enzyme which enables DNA recombination.- the enzyme is encoded by Rag genes.
Deficiency in Rag genes can lead to SCID.
The unused DNA is looped out and removed
What is an epitope?
the region of the antigen that the antibody binds to
What do naive antigen specific lymphocytes need to be activated ?
Antigen (but not just antigen alone- it needs more)
Accessory signal (directly from microbial constituents or from a t helper cell)
What is the structure of the BCR?
It is a transmembrane complex composed of mIg (separate) and di-sulfate linked heterodimers (Ig alpha and beta)
The Igalpha and Igß heterodimers contain immunoglobin fold structure
The cytoplasmic tail of the membrane bound Ig (mIg) is too short for signalling.
The cytoplasmic tails of the heterodimers are long enough to interact with intracellular signalling molecules.
The binding of an antigen onto the mIg causes a structural change which drived signalling by the heterodimers
What are the 2 pathways for antibody production?
- Thymus dependent- T helper cell- all Ig classes. Protein based antigens and broader family
- Thymus independent- microbial constituents- only IgM and no memory
How do you get such antigen receptor diversity?
Recombination
BCR receptor chain is encoded by separate multigene families on different chromosomes. During B cell maturation, these segments are rearranged and brough together.
Variety is brough about by shuffling- this is known as immunoglobin gene rearrangement.
This is what generates the diversity of the lymphocyte repertoire
What are the stages of B cell development?
- Stem cell
- Early pro-B cell
- Late pro-B cell
- Large pre-B cell
- Small pre-B cell
- Immature B cell
- Mature B cell
Selection for self tolerance and productive gene rearrangement at immature stage. If the cells survive they become mature (or naive) B cells (IgM or IgD)
The heavy chain goes vdj rearrangement first, then light chain rearrangement
T-B cell working together
B cell and dendritic cell both have same antigen on their MHC.
T-Cell recognises antigen on MHC Class II with TCR on dendritic cell, activating it (costimulation)
Expands and travels to lymph node.
They binds to B cells which have the same MHC class II with the antigen- this is the second signal (it’s basically calling in the troops).
The B cell becomes a plasma cell.
Cytokine influence on antibody produced
There are different T helper cells (Th1 and Th2)
The types are defined by the cytokines they produce- different cytokines will switch the kind of constant region on the antibody.
The variable region remains the same
The type of T cell that the B cell is exposed to is critical to how antibodies repsond.
What is adaptive immunity?
Improves efficacy of the innate immune response. Focuses a response on teh site of infection and the organism responsible.
It has memory but needs time to develop. The primary response (first encounter) needs days to develop. On repeat infections (secondary response), is faster and stronger.
What happens with the BCR after correct antigen exposure? What are the three possible pathways?
It is stimulated and interacts with T cells. It will travel to the lymph nodes. There are three directions from here.
- Affinity maturation- Antibody response improves
- Memory- becomes stored later for later exposure to the same infection.
- Plasma- B cells which make the antibody
How is a standard membrane protein expressed.
- Genomic DNA
- Primary transcript RNA
- Mature mRNA
- Translation to protein
