Lecture 3- recognition of antigen by b cells and antibody Flashcards
TCRs and BCRS?
B cells and t cells have receptors on their surface which recognise foreign molecules. (T cell receptor, TCR and B cell receptor BCR)
BCR are on B cell surface. They can be secreted and = an antibody.
What are the antibody main functions?
- Bind foreign antigens encountered by host.
2. Neutralize or eliminate foreign invaders.
What is structure of antibody?
An immunoglobulin. They are heterodimers.
They have 2 heavy chains and 2 light chains.
Each light chain is bound to a heavy chain by a disulfide bond and by non covalent interactions such as salt linkages, hydrogen bonds and hydrophobic interactions to form the heterodimer H-L. Similarly the two H-L heterodimers bind by the same type of bonds to form the basic four-chain (H-L)2
Antibody domains?
They have a V domain (variable) in N terminus and C domain (constant) at C terminal.
Heavy and light chains are folded into domains each containing about 110 aa’s and an intrachain disulfide bond that forms a loop of 60 aa’s. The aminoterminal domains bind to antigen (V regions). The effectors functions are mediated by th eother domains.
Describe the proteolytic cleavage by papain?
Papain cuts at the disulphide bonds that link the heavy chains-two identical fragments with antigen binding activity- Fragment antigen binding or Fab fragment
Remaining domain doesn’t bind antigen but does crystallise- Fragment crytallizable or Fc fragment
(fab and Fc fragments)
Where does the antigen bind to the antibody?
At the variable region. The fab region. (the fc part is not involved in recognising the antigen)
What are antigens?
Anything recognised by antibodies. usually proteins. can be dna, lipid and other things though.
Which part of the antigen is recognised by the antibody?
The antigenic epitopes
What are the 2 types of antigenic eptiopes?
1.-Conformational epitopes
Structural, formed by protein folding but may not be a continuous sequence of amino acids.
2.-Linear epitope
Continuous sequence of aminoacids.
What are common epitopes?
Two proteins can have the same epitope on. So an antibody could recognise them both.
(the protein will also have unique epitopes that only that one has, so added specificity)
Which part of the antibody recognises the epitope and what is it also called?
Hypervariable region =
complementary determining region (CDR)
(or is that the part on the antigen?)
What are the forces between the antibody and antigen?
Non-covalent bonds. So if you want a strong interaction you need a lot of these bonds. this is done by close proximity. If they are far away, these will be weak so low affinity. Close=high affinity.
What is cross-reacting?
Talks about how an antibody can still bind to other antigens but maybe not with high affinity. May not fit very well.
What is Avidity of antibody binding?
It’s how strongly the whole antibody is bound to the antigen. Because one antibody can bind with both binding sites to two epitopes on the same particle. So this increases the binding strength/avidity.
Are antibodies made all the time?
No they are made after an infection. You may have low levels circulating but mostly made by B cell when they encounter a pathogen.
Compare the adaptive (antibody) response to innate response?
1.Antibody response:
Acquired - after exposure to pathogen
Specific - for pathogen
Memory - 2nd response bigger and faster
2.Innate immune response:
Immediate - pre-existing
Not-specific - for any one pathogen
No memory - 2nd response same as 1st
What are the 5 main functions the antibody will have?
- Neutralization- antibody prevents bacterial adherence.
- Opsonization- antibody promotes phagocytosis by neutrophil or macrophage.
- Complement activation- activates complement which enhances opsonization and lyses some bacteria.
- Agglutination- Immunoprecipitates a soluble or non-soluble antigen.
- Antibody dependent cell mediated cytotoxicity (ADCC)- Host cells with antigen on cell surface can bind antibodies (eg cells infected with intracellular bacteria or tumour cells). Cells with FcR can bind the antibody (eg NK cell or macrophage).
How does the antibody activate opsonization?
Fc domain binds to FC receptors. It triggers phagocytosis.
ADCC
Mediates extracellular killing. Not phagocytosis.
Potential to remove tumours with antibodies.
What is different between the antibody classes?
These vary in the Fc region: class-specific structural and functional properties.
They are designed to do different things
What are the antibody classes?
IgG= most common
IgM=1st one produced after accounter with pathogen and can cause pentamer linked by J chain and disulphide bonds
IgD-rare not clear what it does
IgA- in gut. 2 subclasses a1 and a2. Dimer joined by J chain.
IgE- produced by mast cells. important in allergy.
What does IgA do?
B cells and antibody are made in bone marrow and then move to secondary lymphoid tissue.
Another major site of B cell activity and antibody production is Mucosal Associated Lymphoid Tissue - MALT e.g. gut
The MALT is particularly associated with IgA
can produce up to 5g/day!!!!!
describe IgA?
It’s the predominant immunoglobulin in external secretions: saliva, tears and mucus.
Is a dimer in secretions – joined by a “J” chain
How does the IgA get into the gut?
A molecule called the poly Ig receptor is found on the basolateral side of intestinal epithelial cells.
This attaches to IgA and is internalised into cell.
Part of the poly Ig receptor is cleaved. The remaining part –now called the secretory component (SC)- allows IgA to be transported into the gut.
SC helps protect IgA from destruction by gut enzymes
