B cells Flashcards
where does haematopoietic development leading to B cells occur?
Takes place in the bone marrow and in the spleen
What do regulatory B cells do?
Regulatory B cells secrete anti-inflammatory cytokines and regulate anti-inflammatory responses and B cell responses
What is humoral immunity and how does it work?
Humor = fluid
Following infection, the plasma contains substances- “antibodies (Ab)”- which neutralise that specific infectious agents or toxins
What are the phases of humoral immune response and what are the components it ends up with?
First is antigen recognition then activation of naive B cells through helper T cells and/or other stimuli
Then what happens is proliferation and differentiation which ends up with several components:
Antibody secretion
Isotype switching
Affinity maturation
Memory B cells
What are an antigen and an antibody?
Rather superficially, an antigen is defined as “anything that can be bound by an antibody”
Antibodies are proteins produced by adaptive immune cells that bind specifically to relatively small parts of foreign molecules known as antigenic determinants or epitopes
Now antigens are also considered any substance that can induce an adaptive/acquired immune response
Antigens can be short peptides, proteins, sugars and lipids etc.
Both antigens and antibodies are incredibly diverse
How does the B cell response show specificity? (What is the structure of an antibody?)
The immunoglobin or antibody Immunoglobulin glycoprotein: Y-shaped Tetrameric 2 identical heavy chains 2 identical light chains Held together by non-covalent interactions and by -S-S- crosslinks (disulphide bonds) between cysteine residues
How is the variable region structured in immunoglobulin?
Within the variable region sequences are concentrated into certain segments called HYPERVARIABLE REGIONS, 3 in the VH and 3 in the VL
Most variability lies in the VH3 domain
CDR- complementary determining regions produce loops with bind to the antigen
How does an antibody bind to antigen?
Using non-covalent interactions
Electrostatic, hydrophobic, van der Waals forces, hydrogen bonds
Depends on the antibody binding site being exactly complementary, sterically (in space) and chemically, with a site on the surface of the antigen
The region on the antigen where the specific antibody binds is called an epitope or antigenic determinant
Antigens can bind in pockets, grooves, on extended surfaces or to protruding surfaces on the BCR CDRs
How do antigenic determinants work?
Conformational determinant- the part od the epitope that binds the antibody depends on the native conformation of the protein, so the protein needs to be folded in order for several elements in the sequence of the proteins to come together to bind to an antibody
Linear determinant- those could be of two kinds.
An antibody could bind to an exposed epitope in the protein, folded, and if we were to denature the protein, that exposed area may remain in one region of the sequence and the antibody is able to bind to that
At the same time an antibody could bind to another region that’s actually hidden by the folding of the protein, and that particular determinant is not is not going to be accessible if the protein is folded; only when it is denatured
How does a B cell design a specific antibody to bind to a specific antigen?
The answer is it can’t
The body generates millions of different B-cells each making a different Ig with random antigen-binding sites
This is possible thanks to various sequential molecular processes including Ig gene rearrangement, selection, receptor editing, and somatic hypermutation
Each B-cell ends up making one antigen-specific Ig randomly
How do B cells expand?
Clonal selection and expansion
Multiple B cells with different B cell receptors
Only one B cell receptor binds to antigen X and gets activated
The antigen, therefore, selects the specific B cell clone which proliferates outnumbering the others
Antigen X-specific B cell clones differentiate into plasma cells secreting soluble X-specific antibodies
Why are antibody responses polyclonal?
Most antibody responses are polyclonal because:
More than one clone of B cells is generated
More than one Ig is synthesised
Because:
Multiple antigens on organism
Multiple epitopes on each antigen
More than on Ig may recognise the same epitope
What are the antibody isotypes?
The different immunoglobulin isotypes are IgG, IgA, IgM, IgE and IgD
The heavy chain is denoted by a different Greek letter
They all have different functions
IgG has the most subclasses IgG1, 2, 3 and 4 in humans
What is isotype switching?
B cells are antigen presenting cells so T cells can help them
B cell- T cell interaction, B cell display a surface antigen, causes the T cell to secrete cytokines that help drive the B cell to proliferate and differentiate into a plasma cell
Class switching of Igs to IgG, A and E
Release of Igs (into the circulation or onto mucosal surfaces)
