B Lymphocytes Flashcards
What are antigens?
Proteins/molecules present on pathogens that induce an adaptive immune response
What are epitopes?
Regions of antigens where receptors bind
What are the two different types of epitopes?
Linear: SEQUENCE recognised by T-cells
Structural: STRUCTURE recognised by antibodies
What is the humoral response?
B-Cell and antibody activity
What is the cell-mediated response?
T-cells and cytokines with killing
What are B-Lymphocytes?
WBCs derived from haematopoietic stem cells that are effector cells of humoral immune system, secreting antibodies and becoming memory cells
What are B-Cell receptors?
BCRs
Antibodies - Unique binding sites that bind to epitopes, attached to transmembrane domains that cause a cascade upon binding.
How many BCRs are there on a single B-cell?
Thousands
What is the structure of a BCR?
Transmembrane complex comprised of monomeric immunoglobulin, and couple of disulphide linked IgAlpha and IgBeta heterodimers each side.
Does the monomeric immunoglobulin in the BCR have a signalling domain?
No
How does the monomeric immunoglobulin in the BCR initiate a signal upon reaction w/epitope?
Structural changes occur in mIg that cause conformation changes in IgAlpha/Beta. Their cytoplasmic tails can then start intracellular signalling
How many antibodies does a human need to produce?
10^10
How many genes code for the production of all antibodies
~25,000
By recombination
What are the 3 types of variable gene segment involved in Antibody production?
Variable (V)
Diversity (D)
Joining (J)
Constant (C)
Describe the structure of Germline DNA that encodes the Ig Light Chain.
In germline DNA 30-40 Variable regions encoded, followed by 5 Joining regions and a constant region
How is the Ig Light chain expressed?
3 Steps
- Germline DNA rearranged as B-cell develops (in marrow)
2 V regions and a J region randomly selected along with constant region. - Gene transcribed to RNA with alternative splicing patterns. Results in mature mRNA w/ one V, J, and C region
- Translated into Kappa chain polypeptide.
What is the enzyme that produced recombinant DNA?
V(D)J Recombinase
What gene codes for V(D)J Recombinase?
Rag genes
What does Rag gene deficiency lead to?
SCID
Severe combined immunodeficiency
What is the structure of Heavy chain germline DNA?
65 V
27 D
6 J
9 C
How is the Ig Heavy chain expressed?
Rearrangement of germline DNA
Transcription (1 V, 1 D, 2 J, 2 C)
Alternative splicing (V,D,J,C)
Translation
What are the differences in expression between the light and heavy chain?
D region only found in heavy chain.
Name the stages of B-cell development
Haematopoietic Stem Cell Early pro-B cell Late pro-B cell Large pre-B cell Small pre-B cell Immature B cell Mature B cell
What happens to Ig that recognises self?
Selected out during maturation to mature B cell
When is surface Ig first present on a B-cell?
Immature B-cell (IgM present)
In what stage of development of the B-cell are Light Ig chains first rearranged?
Small pre-B cell
Rearranged by Immature B-cell
In what stage of development of the B-cell are Heavy Ig chains first rearranged?
DJ rearranging in Early pro-B cell
V-DJ rearranging in Late pro-B cell
What are the 3 possible pathways when a B-cell binds to an antigen?
Affinity maturation: Antibody response improves
Memory Cell: stored for later exposure
Plasma cell: Produced to secreet antibodies
How can a plasma cell be identified?
Many ER and ribosomes present to produce antibodies
What is required for Naïve B-cells to react with antigens?
Signal from T helper cell or microbial constituents
What are the 2 types of antigen a B-cell can recognise?
Thymus dependent: All Ig classes w/memory
Thymus independent: IgM without memory. Requires microbial constituent signal
What do T helper cells do when the recognise antigens on B-cell surface?
Release cytokines to drive B-cells to undergo clonal expansion
What effect do might cytokines have on B-cells?
Different cytokines lead to different types of antibody (Ig) production by changing the type of Constant region (variable region remains same)
What is Ig Class Switch?
When the constant region of an antibody is changed by the effect of cytokines secreeted by T helper cells
When does somatic hypermutation and affinity maturation occur?
Inbetween exposures - Response improves
What is Somatic hypermutation and affinity maturation?
AID (activation-induced deamination) causes point mutations in the VDJ region.
What problems can B-cells cause?
Autoimmunity, allergy, cancer
