PMI02-2005 Flashcards
What is the cell lineage of a B cell?
Pluripotent haematopoietic stem cell
Common lymphoid progenitor
Pre-B cell
Where do mature naive B cells migrate to after development in bone marrow?
Lymph nodes
Spleen
Where do B cells develop?
Bone marrow
List some functions of antibodies.
Inhibit attachment of pathogens to host tissue
Activate complement
Enhance phagocytosis
Induce degranulation of mast cells, basophils, eosinophils
Describe the basic structure of antibody.
Y-shaped
2 identical heavy chain polypeptides (50-60k MW) linked by disulphide bonds
Each heavy chain linked to one of 2 identical light chain polypeptides (25K MW)
Which part of the antibody binds to antigens?
Fab fragment
Which part of the antibody varies within a class?
Fab fragment
Which part of the antibody varies between classes?
Fc fragment
Describe the molecular structure of an antibody.
N terminal part of heavy chain forms 2 protein domains linked by a more flexible hinge region to 2 C terminal domains
Heavy N terminal domains fold with light chains to give 2 identical binding sides (Fab portions)
C terminal parts form Fc portion
Which of the C or N terminals mediates functions of antibodies such as complement activation?
C terminal (forms Fc portion)
What is an epitope?
Specific site on an antigen that binds to an antibody
What is an immune complex?
Antibody bound to antigen
May be a pair or a huge complex of many antibodies and antigens
What is the molecular part of the antibody that binds to an antigen?
3 loops (CDRs) between β-strands in the variable/Fab region
What are complementarity determining regions?
Loops between β-strands of the Fab region which bind to antigens
How are the CDRs numbered? Which often contributes most to binding affinity and specificity?
Numbered ascending from N (CDR1, CDR2, etc) to C terminal
CDR3 (also often the largest)
What are some effector functions of antibodies?
Activation of complement
Stimulate phagocytosis
Transport to mucosal surfaces to prevent invasion
Transfer across placenta
Induce degranulation
What role do antibodies play in complement activation?
Activate C1q when bound to antigen
Leads to lysis (MAC) or phagocytosis via complement of Fc receptors
How do immunoglobulin classes physically differ?
Number of Fc immunoglobulin domains
Whether or not they are monomeric or not
Which immunoglobulin class is most abundant in the serum? What about subclass?
IgG
IgG1 specifically (9mg/ml)
Which immunoglobulin class is most abundant at mucosal surfaces?
IgA
Which immunoglobulin can move across the placenta?
IgG
Describe the IgM class.
Pentameric
Each monomer has an additional immunoglobulin domain in the Fc region (4 in total)
Monomers linked by 2 disulphide bonds between CH3 and CH4 domains
Ring completed by a J chain linked by disulphide bonds
What is the J chain important for?
Oligomerisation and stabilisation of an altered conformation of CH4 domain to allow closer packing of monomers in IgM
Dimerisation of IgA
Which immunoglobulin classes are monomeric?
IgD
IgG
IgE
Which classes of antibody are produced by all newly activated B cells?
IgM
IgD