Title: ? Structure
1Antibodies
? Structure ? Diversity ? Function ?
Characteristic and Function of various classes of
antibodies ? Artificial antibodies
2Basic concepts ----Stimulation of B cells with
antigens leads to differentiation of the B cells
to plasma cells. ----Antibodies are glycoproteins
secreted by plasma cells. ----Antibodies can
specifically bind to the corresponding
antigens. ----Antibodies are secreted into the
serum to make up the circulating antibody
pool. ----Antibodies are also called
immunoglobulins (Ig). ----secretory Ig membrane
Ig
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4The structure of immunoglobulins 1. Basic
structure (1) a common structure of four peptide
chains H2L2 linked by disulfide bonds two
identical light (L) chains, polypeptides of about
25,000 molecular weight, and two identical heavy
(H) chains, larger polypeptides of molecular
weight 50,000 or more Heavy chain 5 types
(isotype a, g, m, d, e) Light chain 2 types
(k, l)
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62. Three functional regions Variable region,
VH/VL, Fv to bind to the antigens VH and
VL hypervariable regions, HVR----antigen
binding sites----complementarity-determining
regions, CDR framework regions,
FR1-4 Constant region, CH/CL Hinge region
7Functional Regions of Immunoglobulins
83. enzyme digestion Papain Fab, Fc
Pepsin F(ab)2, pFc
The enzyme digestion products of Immunoglobulins
9Antibody Classes and Antigenic Determinants on
Ig 1. Classes and Types Class Antigenicity of
the heavy-chain constant region----IgG, IgA, IgM,
IgD, IgE Subclass Antigenicity of the
heavy-chain/number and location of disulfide
bonds----IgG1-4 Type Antigenicity of the
light-chain constant region----k, l Subtype
different arrangement of aa in the light-chain
constant region----l14
102. Antigenic Determinants on Ig Isotype
constant-region determinants----non-genetic sign
Allotype different alleles----genetic sign
Idiotype, Id Idiotope?Anti-Id
Isotype Allotype
Idiotype
113. Accessory structures (1) J chain
(Joining chain) (2) Secretory piece,
SP 4. Domain (1) Compact dimensional
globes formed by intrachain disulfide bond in Ig
molecule (V/C/H/L) (2) b-sheet, b-barrel,
immunoglobulin fold (3) CDRs(complementarit
y-determining regions, hypervariable regions),
FRs(Framework regions)
12Diagram of an immunoglobulin light chain
depicting the immunoglobulin-fold structure of
its variable and constant domains.
13General structures of the five major classes of
secreted antibody.
14Main Characteristic and Biological Functions of
Ig 1. Main Functions (1) specifically bind to
the corresponding antigens Fv (2) activate
complements (3) bind to FcR opsonization
allergic reactions
antibody-dependent cell-mediated
cytotoxicity (ADCC) (4) cross the placenta and
the mucosal surfaces (5) regulate immune response
15Figure 1-24
16CDR of Ab binds to the epitope of Ag.
17Opsonization mediated by antibodies
18antibody-dependent cell-mediated cytotoxicity
(ADCC) mediated by NK cells
192. Characteristics and functions of various
classes of antibodies (1) IgG four
subclasses, widely distributed, the most abundant
class in serum, the only class that can cross the
placenta (2) IgM five monomer subunits
linked by J chain, the first class produced in a
primary response to an Ag, diagnostic sign for
intrauterus and recent infection (3) IgA
monomer serum dimer external secretions (4)
IgD low levels, the major membrane-bound Ig
expressed by mature B cells (5) IgE
extremely low average serum concentration,
cytophil, hypersensitivity/antiparasitic defense
20mIgM
mIgD
immature B cells mature B cells
activated/memory B cells
21Production of Antibodies 1. polyclonal
antibody, PcAb 2. monoclonal antibody, McAb
3. engineering antibody antibodies
produced by using DNA recombination technique and
genetic engineering means including
human-mouse chimeric Abs, reshaped Abs,
bispecific and bifunctional Abs, small molecule
Abs etc
22Production of Polyclonal Antiserum
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24Humanization (Chimeric/Reshaped Antibody)
25 the structure and key biological function of
immunoglobulins antibody diversity the
concepts and the characteristics about monoclonal
antibodies the concepts and the
characteristics about production of monoclonal
antibodies