B-cells Flashcards
What are B-cells?
B-cells are cells that arrise in the bone marrow thry recognise antigen via B-cell receptors and produce antivodies
What is the B-cell response?
A naive B-cell is activated once it binds an antigen- activated Bcells can become plasma cells or memory cells- these cells can reporduce via clonal expanssion
What are plasma cells?
Cells that produce antibodies (2000/second)
What are BCRs?
B cels receptors- theyre antibodies that are membrane bound
What is the structure of a BCR?
Antibodies made of two light and two heavy chains that have cosntant and variable regions theyre all held together by disulfide bonds (known as the hinge(
Where are antigen binding sites in antibodies?
Variable regions
Antobodies have two segments what are they?
Fc and FAB fragments
What is the Fc region of antibody?
The constant region with heavy chains
What is the FAB region?
Fragment of antogen binding found in the variable zone of the antibody
How is antobody diversity produced?
VDJ recombination
How does VDJ recombination create diversity?
Antobodies have loci that are spliced together but they can be spliced together in varying combinations leading to variety in antibodies
How is VDJ recombination of a light chain work?
Start with germ line DNA and splice V and J segements together RNA is then produced which is spliced to join the constant segment- then translated to a light chain
How does VDJ recombination occur for heavy chains?
V D and J regions spliced together into RNA then join constant region and are transcribed to antibodies.
Same as light chain but plus D regions
Where does VDJ recombination occurs?
At recombination signal sequences
Where are recombination signal sequences (RSS) found?
Between/ flanking VDJ segments
Where does VDJ recombination occur in the body?
Bone marrow
What happens when mature B-cells are activated by antigens?
They differentiate into plasma or memory cells
How can B- cells be activated?
Only by helper T-cells for the same antigen
Two types of B-cell activation?
Thymus dependent (T-cell) or thymus independent (no T-cell)
What is thymus independent activation?
Antigen binds directly to immune receptors on the B-cell
How does thymus dependent activation work?
TCR binds the epitope (antigen) then antigen is internalised MHC class 2 molecules present MHC through TCR and release cytokines. MHC activates B-cells
How do T-cells cause activation of B-cells?
T cells express CD40L which stimulates B-cells to proliferate and become plasma cells. Also release iL-4 droves proloferation and il-5/6 ther drive plasma cells
Where does B-cell proliferation occurs?
Germinal centres of the lymphnodes
How does B-cell proliferation occur in lymphnodes?
B-cells move into lymphnode brcoming trapped in T-cell zone so they come in contact. They then move to the germinal centre which is made up of proliferating B-cells
What happens in germinal centres?
B-cells undergo:
Somatoc hypermutation
Affinity maturation
Class switching
What is somatic hypermutation?
Introduces point mutation in the variable region of the light and heavy chain-further diversifies antibodies.
How does somatic hypermutation occur?
Its occurs using a cystine deaminase called AID- introduces nicks in DNA that are repaird leading to point mutations -requires single strand DNA
What is affinity maturation?
Process of B-cell selection based on their abilities to bind to the antigen
What happens to cells that arent specific enough for affinity maturation?
They lack signals need to survive so die
What is antibody class switching?
Antibody classes switch from producong IgM antibodies to produces IgA to IgG to IgE. Become more specific with different C regions
There are 3 types of antibody functions what are they?
Neutralisation,opsonisation and complement activation
Whatare 3 examples of antibody neutralisation?
- antobodies bind toxins
- antibodies can block viral binding
- can block adherence to host cells by bacteria
What is opsonisation?
An example is phagocytosis which is done by macrophages neutrophils
What is complement activation?
Ehancement of opsonisation leading to lysing bacteria
What are Fc receptors?
They bind to the Fc portion of the antibody found on NK cells, mast cells and neutrophils- specific to each antobdot isotype
What are the 4 antibody subclasses?
IgM
IgG
IgA
IgE
What are IgM?
First low affinity antibodies expressed
What are IgG?
Opsonises pathogens for phagocytosis
What are IgE ?
Antobodies that localise with mast cells on the mucosa
Why do we need vaccination?
As the humoral immune system progresses it cause higher affinity enzymes to ne produced faster
What can B-cells differentiate into?
Plasma cells-release antibodies
Memory cells- for next time
What is BCR?
B-cell receptor a membrane bound antibody
Where are antigen binding sites found on BCRs?
Found within the variable regions
What determines isotype of an antibody?
Carboxy terminus of the heavy chain
What are Complimentary determining regions? (CDRs)
These are where the antigen binds
How many CDR loops on an antigen?
3
CDR1/2 found on V segment of light chains
CDR3 is the most variable and found on the heavy chain
How is antibody diversity generated?
VDJ recombination
How does VDJ recombination occur?
It’s occurs at recombination signal sequences (RSS) RSS are brought together by the RAG complex which opens DNA allowing palindromic sequences to be added, then nucleotides are added by TdT unpair nucleotides are excised and DNA repaired.
Where do you find RSSs?
At 23bp heptamer
-23bp nonamer
How does VDJ recombination generate diversity?
Through combinational diversity and by junctions diversity.
How do you generate combinational diversity in VDJ?
Through different combinations of gene segements
How does junctional diversity work?
Generates diversity via the addition of nucleotides during recombination
Where do B-cells develop?
In the bone marrow
How can B-cells be activated?
Thymus dependently
Thymus independently
How does thymus dependent activation work?
APC binds epitope and internalises. Presented on MHC2 molecule. T-helper recognises through TCR and release cytokines. B-cell then release specific antigens
What does CD40L do on T-cells?
Stimulates B-cells to proliferate and become plasma cells
What does interleukin-4 do?
Drives B-cell proliferation
What do interleukin-5/6 do?
Drives plasma cell production.
What happens in a germinal centre?
B-cell passed through T-cell zone and become trapped until contact a T-cell presented antigen. They then move into the germinal centre where they displace old B-cells into the mantle.
What happen to B-cells in germinal centres?
They undergo
Somatic hypermutation
Affinity maturation
Class switching
How does somatic hyper mutation occur?
Induces point mutations in the variable regions of antibodies. This is by AID (cystine deamination) introducing a nick in the DNA that is then repaired.
What is affinity maturation?
Mutated B-cells are selected based on their ability to bind antigen. More survival signals sent to those who aren’t more specific.
What is class switching?
DNA recombination that Changes the constant region of the heavy chain. IgG IgA and IgE
What do IgG antibodies do?
Opsonise pathogens for phagocytosis
What do IgA antibodies do?
Functions on epithelial surfaces -neutralisation of toxins and binding prevention
What’s the role of IgE?
Localise mast cells
What does BLIMP 1 do?
Switches off proliferation and affinity maturation
