B lymphocytes Flashcards
How many days does it take for the adaptive immune response to develop + become effective?
4-7 days
What are 2 forms forms of the adaptive immune response?
- Humoral: B cells, antibodies
- Cell-mediated: T cells, cytokines, lysis of pathogens
Where do B cells mature?
one marrow, whereby they express specific B cell receptors (BCR)
Where does antibody production following B cell activation and differentiation occur?
peripheral lymphoid organs
What are the 4 stages of B cell maturation?
Pro-B Cell -> Pre-B Cell -> Immature B Cell -> Mature B Cell
What is the B ell receptor?
transmembrane protein complex composed of: mIg + Igα/Igβ
What is the function of mIg that forms the B cell receptor?
central larger immunoglobulin molecule, cytoplasmic tail too short so not involved in signalling
What is the function of mIg that forms the B cell receptor?
central larger immunoglobulin molecule, cytoplasmic tail too short so not involved in signalling
What are Igα/Igβ that form the B cell receptor?
dil-sulfate linked heterodimers, contain immunoglobulin-fold structure. cytoplasmic tails of Igα/Igβ long enough to interact with intracellular signalling molecules
Which structures forming the B cell receptor interact with intracellular signalling molecules?
Igα/Igβ - cytoplasmic tails. mIg cytoplasmic tail too short
Which structures forming the B cell receptor interact with intracellular signalling molecules?
Igα/Igβ - cytoplasmic tails. mIg cytoplasmic tail too short
What does the unique binding site of B cell receptors bind to?
antigenic determinent/ epitope
How are BCR coded for on chromosomes?
kappa and lambda light chains and the ehavy chain are encoded by separate multigene families on different chromosomes - during maturation, segments are rearranged and brought together to form BCR (immunoglobulin gene rearrangement)
What are 4 types of segments within genes responsible for encoding the BCR chain?
- variable, V
- diversity, D
- joining, J
- constant, C
Which chain of the BCR is the diversity gene segment responsible for?
heavy chain only
In summary what generates the diversity of the B cell lymphocyte repertoire?
immunoglobulin gene rearrangement - occurs during maturation of B cells in the bone marrow
What type of DNA is involved in the synthesis of prototypical B cell membrane proteins?
Genomic DNA -> transcription -> primary transcript RNA/pre-mRNA -> Splicing -> Mature mRNA -> trnalsation -> membrane protein
What is the process resulting in light chain synthesis?
Germline DNA -> rearrangement of V and J segments involving VDJ recombinase -> B cell DNA -> transcription -> primary trancript RNA/pre mRNA -> splicing -> mature RNA -> translation -> light chain polypeptide (kappa or lambda)
Which enzyme is important in rearrangement of V+J segments of germline DNA important for heavy and light chain synthesis?
VDJ recombinase
What happens to unused DNA during joining of gene segments for light chain synthesis?
looped out and removed
What is the process of heavy chain synthesis from gene encoding?
Germline DNA –> rearrangement of V and J segments involving VDJ RECOMBINASE –> B cell DNA –> Transcription –> Primary transcript RNA/pre-mRNA– (Alternative Splicing) –> Mature mRNA –> (translation) –> Heavy chain polypeptide
Which DNA are B cell receptor membrane proteins derived from?
genomic DNA
Which DNA are B cell receptor heavy and light chain proteins derived from?
germline DNA
Which DNA are B cell receptor heavy and light chain proteins derived from?
germline DNA
What is meant by alternative splicing?
involved in heavy chain synthesis - results in different mature mRNA, as mRNA express different genes (e.g. may have different constant region genes present)
What happens to a B cell if it doesn’t meet an antigen?
cell death
What can happen to antibody specificity and class over time?
may keep specificity but change class
What is clonal expansion?
mature lymphocytes (T or B) migrate to periphery, unique specific antigen receptor binds antigen - activates cell + proliferates to clone of cells with same receptor
What is the difference between a plasma cell and a memory cell?
plasma cells produce lrage amounts of antibodies, while memory cells remember antigens and create secondary immune responses
What do naive antigen-specific lymphocytes need to be activated by antigen?
Cannot be activated by antigen alone, require accessory signals either from:
1. microbial constituents - thymus independent
2. helper T cells - thymus dependent
What do naive antigen-specific lymphocytes need to be activated by antigen?
Cannot be activated by antigen alone, require accessory signals either from:
1. microbial constituents - thymus independent
2. helper T cells - thymus dependent
Which class of immunoglobulin can be produced by thymus independent accessory signals + antigen activation to lymphocytes?
IgM only
Which class of immunoglobulin can be produced by thymus dependent accessory signals + antigen activation to lymphocytes?
all immunoglobulin classes
Which type of antigen activation of lymphocytes forms memory cells?
thymus dependent only - not formed wih thymus independent signalling
What is the main difference between the process of thymus independent accessory signalling with antigen ativation vs thymus independent?
- independent: antigens directly activate B cells without the help of T cells
- dependent: membrane bound BCR binds with antigen, is internalised + delivered to intracellular sites
- antigen is degraded into peptides, peptides associated with self MHC class II form complex which is expressed at cell surface
- T cells with compleentary TCR recognises the complex, then secretes lymphokines
- B cell then enters cell cycle, forming clone of cells with identical BCRs + differentiating into plasma + memory cells
What are the 7 stages of how T cells aid B cells in thymus dependent antibody production?
- Antigen cross link with BCR induces signal 1- ↑MHC II, ↑B7
- Antigen is internalised and degraded, and the peptide-MHC II complex is presented
- T cell recognises complex and co-stimulation by B7 and CD28 interaction -> activation of T cells
- Activated T cell expresses CD40L -> the interaction between CD40L and CD40 (expressed by B cell) induces signal 2
- Activated B cells (CENTROBLAST) express cytokine receptors
- T cell derived cytokines bind to receptors on B cells
- B cells proliferate and differentiate into antibody secreting plasma cells
Which 2 things are upregulated in the B cell as a result of signal 1 in the thymus dependent antibody production?
MHC II, B7
What 2 things activate T cells during thymus dependent antibody production?
- B7
- CD28
What do T lymphocytes increase their production of during thymus dependent antibody production?
CD40L
What process induces signal 2 in thymus dependent antibody production?
interaction between CD40L (expressed by T cell) and CD40 (expressed by B cell)
Which part of immunoglobulins remains constant and which changes during class switching?
variable region (hence specificity) remains constant, but constant region changes from the original IgM
Which 2 Ig classes are induced by IL-4?
- IgG1
- IgE
What is the action of IL-5 on antibody switching?
augments production of IgA
Which 2 immunoglobulins are induced in antibody switching by IFN-gamma?
IgG3 and IgG2a
Whcih 2 immunoglobulin classes are induced by TGF-beta in antibody switching?
IgG2b and IgA
What are 3 ways in which the secondary immune response i.e. subsequent encounters with an antigen differs from the primary response?
- more rapid
- higher amount of antibody produced
- higher affinity for antigen
Which cells are responsible for the secondary immune response?
memory B cells
What is the lag period for the primary immune response vs secondary immune response?
- primary = 4-7 days
- secondary = 1-3 days
What is the time of peak response for the primary immune response vs secondary immune response?
- Primary = 7-10 days
- Secondary = 3-5 days
Is antigen processing thymus independent or dependent for the primary immune response?
both
Is antigen processing thymus independent or dependent for the secondary immune response?
dependent
What is meant by polyclonal antiserum?
all antigenic epitopes induce an immune response -> many different B cells activated -> different antibodies produced i.e. mixture of antibodies directed to several antigenic determinants
How can monoclonal antibodies be extracted?
combining plasma cells with myeloma cells to form hybridomas
What is a plasma cell?
a fully differentiated B-lymphocyte (white blood cell) which produces a single type of antibody.
What is ap plasmacytoma?
clone of malignant plasma cells
What provides the genetic variability allowing the body to generate an immune response to every pathogen during its lifetime?
The hypervariable regions of receptors achieve their diversity through** genetic recombinations during development (in utero**). These include V, D, and J gene rearrangements, with random addition of nucleotides by terminal deoxyribonucleotidyl transferase.
