lecture 3- antibody structure Flashcards
___ is the secreted form of B-cell receptor
immunoglobulin (antibody)
describe BASIC structure of an antibody
2 identical heavy chains & 2 identical light chains
- multiple disulfide bonds, both intra- and interchain
- antigen binding site made of 1 heavy chain and 1 light chain
- structure allows for flexibility and binding for a range of antigens
describe antibody structure in deeper understanding
heavy chain = 1 constant region &1 variable region
light chain= 1 constant region & 1 variable region
- Fc region = (fragment crystallizable), first to be cloned and sequenced – only a heavy, constant chain
- Fab = (fragment antigen binding) — variable and constant heavy chain & variable and constant light chain
- Fc associated with a receptor – Fc determined what kind of isotype
the membrane-bound form of the BCR co-resides with signaling molecules _____
IgB (beta) and Iga (alpha)
without them, can’t signal or be expressed on cell surface
antigen contact by antibody is mediated through the ___ of the heavy and light chains
explain
hypervariable loops
- antigen contacted by six hypervariable loops- 3 in light and 3 in heavy chain – called complementary determining regions (CDR)
- most of the diversity between antibodies is in these regions
the highest number of antigen-antibody contacts are usually with this CDR region
CDR3
where are the CDR regions?
at very distal end of molecule in antigen-binding site
- 6
Fab segement gives antibody ___ and Fc gives it ___
specificity
function
conformational determinant
Certain antibody specificities only work on folded proteins, when denatured, the antibody would not work- epitope would fall apart
- Determinant lost by denaturation
name the 5 isotypes of antibodies
IgM
IgA
IgD
IgG
IgE
name the isotypes that multimerize
IgM- pentamerize when with J chain
IgA- dimerizes when with J chain
which is the first antibody isotype expressed
IgM
Which region of the antibody molecule is changed when the cell switches isotypes?
Fc
define affinity
how tightly one molecule binds to another molecuel
define avidity
affinity (x) how ever many interactions there are- the collective affinities through multimeric interactions (dimeric IgA has twice the avidity as monomeric IgA)
Which antibody isotype has the greatest avidity?
IgM
function of IgA
transport across mucosa, neutralization
function of IgD
antigen receptor on naive B cells, sensitizes basophils
function of IgE
immediate hypersensitivity, sensitizes mast cells
function of IgG
neutralization, opsonization, complement activation, neonatal immunity (crosses placenta)
function of IgM
antigen receptor on naive B cells, complement activation
Consider the implications of deficiency in any of the isotypes.
- Would lose the most functions if lost IgG
- IgM is the first, needed to facilitate isotype switching
- Without IgA- impairs mucosal immunity
monoclonal antibody generation
- need a source of antigen-specific B cells
- can grow an infinite number of these B cells in vitro- generate antibodies
- were originally developed in mouse cells
- humanized antibodies now without mouse proteins
the generation of antibody diversity is due to:
(the first 2)
1- combinational diversity (at core of gene rearrangement)
. multiple germ line segments
. multiple heavy and light chains
2- junctional diversity
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