lecture 14: B cells and their antibodies Flashcards
(28 cards)
what is the molecular mass of antigens
antigens are often >10,000 Da but can be of low MW
what are the five different types of antibodies found in the B cell receptor complex
IgM = can be secreted and activate complement
IgD = signalling molecule, helps activate B cell
IgA and IgB = not antibodies, they are signaling domains, help B cell recognise when the B cell has contacted antigen
IgE
when does isotype switching occur
during the immune response
what occurs during the B cell receptor gene arrangement
bone marrow –> blood –> lymph node
- T cell and B cells being their life in the bone marrow, B cells complete their lives in the bone marrow whereas T cells need to move to the thymus
- migrate to blood, lymph nodes and spleen and wait for the correct signals to start producing antibody
- particularly in the spleen and sometimes the lymph nodes isotype switching can occur during the immune response
- as B cells are dividing some will start producing plasma cells of the original isotype and some can be stimulated to switch the type of isotype or class they produce
- B cells when they emerge from the blood shouldn’t be autoreactive and they should express some sort of antibody on their cell surface and they will migrate to the blood, lymph nodes and spleen
function of BCR
- almost all B cells express a unique B cell receptor (BCR)
- this enables the recognition of a wide variety of antigens
how does the production of unique antibodies occur
- antibodies variable sequences are the result of DNA rearrangements
- all cells contain ‘germline’ sequences for antibody proteins, but these cannot be expressed until they are rearranged
- only B cells rearrange antibody germline sequences
- this results in the production of unique antibodies in most B cells
how is the variable part of the antibody produced
- B cells like all other genes have these variable genes lying together in the chromosome
- sometimes during rearrangement, some the DNA is looped out and lost forever bringing these genes together to give you the unique part of the antibody which is the variable part
- because this is random, B cells often differ from one another in which genes they have chosen to produce in the variable part
what are the D genes in heavy chain
- heavy chain is more complicated because it has a series of D genes
- constant region which can switch during immune response
- rather labile and can change
B cells are activated by:
- Recognition of antigen
- CD4 help
how does CD4 help, activate the B cells
- B cell interaction with CD4 cell, lets the CD4 cell known its the right B cell, only then can the B cell move on to the next phase
- the only B cells that will get help are the ones who present a peptide they got from the engulfed antigen to the CD4 cells
how does the recognition of antigen help activate B cells in heavy chains
–> want to make sure the B cell is producing the right type of antibody and not the wrong type that will recognise an important receptor in our body
- B cell comes into contact with antigen, imparts signal into the B cell (transmitted by IgA and IgB –> detect movement and transmit signal downwards)
- transmits downwards a signal to the nucleus (signal one), not going to be on, unless it receives help to overcome the checkpoint, helper cell needs to be activated by antigen presenting cells
How does the helper cell know its the right B cell?
= the binding of antigen helps the B cell drag the antigen in and process it down to peptides
- peptides produced help stimulate CD4 T cell through MHC2 (way of knowing that the right B cell will be given help)
- only give B cell help which has bound antigen
what cells express BCR
- Memory B cells express BCR
- plasma cells do not express BCCR
how do you differentiate between the primary immune response and the secondary immune response
- Primary response
- More IgG than IgM but not as exaggerated (less than secondary response)
At the point where IgG is higher
- they have been vaccinated
or
- they’ve seen the organism before
–> so can help distinguish between primary and secondary - secondary response
- IgG goes way higher, able to circulate around the body for long periods of time
- secondary stimulus the IgG to IgM is much higher
why is IgG more dominant in the secondary response
- class switching has already happened during the primary response
- in the secondary response, memory B cells have already undergone class switching to IgG, so they don’t need to start from scratch
what are the functions of the different antibodies
- enters tissues readily. crosses placenta
- IgG
- IgA
–> IgA (monomer) = serum form
–> secretory IgA (dimer) = mucosal protection - complement activation
- IgM
- IgE = parasites/allergy
- IgD = unknown
what chain does class switching occur in
heavy chains
B cell tolerance
- B cells are checked to determine if they bind self-antigen
- check performed while B cell is still immature
- immature B cells that bind self-antigen die by apoptosis
how can antibody be presented
can be membrane bound (B cell receptor, BCR) or secreted
what is the sole purpose of B cells
to make antibody
what happens during B cell maturation
- includes negative selection within the bone marrow which eliminates developing B cells that recognize self antigen
- once they leave the bone marrow, they migrate between lymph nodes and spleen where they meet the specific antigen recognized by their B cell receptor = activation, proliferation and differentiation into mature, antibody secreting cells called plasma cells
- B cell activation requires a surface receptor, can bing antigen directly
B cell receptors
- made of membrane bound antibodies
- mature, naive B cells attach a type of antibody (IgM or IgD) to their cell membrane so that part of the antibody that binds to antigen is facing outwards
- very little of the receptor extends into the cytoplasm, so for signal transduction to occur the BCR must us IgA / IgB (integral membrane proteins) = hetrodimer proteins
hetrodimer protein complex + transmembrane antiboy = BCR
antibody structure
- all have basic structure composed of 4 polypeptide chains: two identical heavy and two identical light chains
- heavy and ligh chains are connected to each other by disulfide bridges
- heavy chains are structurally distinct for each immunoglobulin class or subclass
- both light and heavy have two different regions
what are the two regions found in light and heavy chains
- constant region
- amino acid sequences that do not vary significantly between antibodies of the same class - variable region
- have different amino acid sequences and these regions fold together to form antigen binding sites
antigen binding
- the 4 chains are arranged in the letter Y with a hinge region which allows the antibody to be more flexible to adjust to different antigens
- the light chains contains hypervariable regions that help confer the ability to bind a specific antigen
- antibody binds to antigen at antigen binding site in Fab region of the antibody
