IMMUNOLOGY

Bios 328
a textbook-based study of immunology
Spring 2003

http://www.lehigh.edu/~sk08/Courses/Bios328/mainpage.htm
FIRST HALF OF TODAY’S CLASS: THE IMMUNOGLOBULINS
 A quick overview of the five immnoglobulin “classes”

• IgG ( globulin): the prototypic immunoglobulin.

All three general functions (Ag binding, complement
activation, stimulation of phagocytosis) occur.

• IgM (macroglobulin): often the first

• IgA: the secretory immunoglobulin
• IgD: regulatory?
• IgE: functions with parasites and allergens
IgG ( globulin)
IgG is the principal immunoglobulin of the secondary
response.

IgG is the principal immunoglobulin of the adult (but not

the neonate.)

IgG constitutes 80% of the circulating immunoglobulin in

the adult.

The concentration of IgG in serum is high: 8-16 mg ml-1.

The architecture of IgG is simple:

two  chains and two  chains or
two  chains and two  chains.
IgM (macroglobulin)
• a pentamer (in secreted form) attached by disulfide bonds
between the C4 and C3 domains of adjacent heavy chains;
in addition, there is a single J-protein.

•IgM is the first immunoglobulin to be synthesized in a

primary response.

•The concentration of IgM in serum is ~ 1.5 mg ml-1.

•IgM is the first immunoglobulin to accumulate in the serum

of neonates.

•IgM has a high valency which contributes to agglutination.

Also, multimeric nature contributes to effective complement
activation.
Some visual reinforcement…
Some more visual reinforcement…
co-los-trum \kc-‘läs-tram \ n \
[L. beestings] (1577) :

milk secreted for a few days

after parturition and
characterized by high protein
and antibody content
 IgA (the secreted antibody…)
Most often a dimer; sometimes a tetramer (or a trimer).

Multimers united by J-protein.

Secretion requires addition of “secretory component” produced in mucosal

epithelial cells (in digestive, respiratory, genital, breast tissues and salivary and
lacrimal glands).

Plasma cells secrete the Ab;

deliver IgA to epithelial cells having poly-Ig-receptor on their
surface.
The poly-Ig-receptor is cleaved and the component that stays
associated with IgA is the “secretory component.”
MW = 70,000 daltons; composed of 5 immunoglobulin-like
domains;
binds to constant regions of heavy chains.

Movement of the receptor from one surface to another is transcytosis.

Visual reinforcement…
IgD and IgE
IgE is extremely rare.
IgD is very rare.
0.0003 mg ml-1 serum
0.03 mg ml-1serum
IgE functions against
What does this imply?
parasites.
In the absence of para-
sites, IgE responds to
allergens.
IgE

IgE is extremely rare.

IgE functions against
parasites.
In the absence of para-
sites, IgE responds to
allergens.
And, there are subtypes, too
Hinges versus domains…

• Hinges contribute to
flexibility. They contain
cysteine and proline.
Cysteine provides
interchain linkage.
Proline cannot be
incorporated into
secondary structure.

• Immunoglobulins without
hinge regions have an
extra domain.
Isotypes, allotypes, & idiotypes
• ISOTYPE: one of the five (, , , , ) major kinds of
heavy chains in immunoglobulins. Note that the
differences among the isotypes are in the constant region.
Indeed, different isotypes can share common variable regions!
(Think about that.)

• ALLOTYPE: the allelic variation seen at loci specifying the

light and heavy chains of immunoglobulins.

• IDIOTYPE: The set of antigenic determinants (idiotopes)

characterizing each unique antibody ( or T-cell receptor). Idiotopes
are single antigenic determinant(s) in the variable domains
of an antibody (or T-cell receptor). Idiotopes are generated by the
unique amino acid sequence specific for each antigen.
Isotypes, allotypes, & idiotypes
 IMPORTANT
• One B-cell makes one type of antibody.
(More exactly, one B-cell makes one idiotype.)

• (This equation is the basis of monoclonal antibodies

but we are going to ignore monoclonals for the time being. )

• Ig’s first appear on the surface of B-cells; there they

are selected.

• The B-cells mature to plasma cells and secrete

antibodies with the same specificity (i. e., same
idiotypic identity; same antigen specificity.)
Visual reinforcement…
Visual reinforcement…
• The carboxy terminus of the
mIg, penetrates into the
cytoplasm by only a few amino
acids. But mIg is always
associated with pairs of the
dimer Ig- / Ig-.

• These associated dimers have

longer carboxy tails, 61 amino
acids and 48 amino acids
respectively. The tails contain
tyrosine residues which can be
phosphorylated by kinases; the
phosphorylated or un-
phosphorylated states constitute
a molecular switch conforming
to an on / off switch.

• (Immunological phenomena
affected by kinases tend to use
tyrosine as the receptor of
phosphates while other cellular
phenomena tend to use serine
or threonine.)
Time to review…
 Time to review…

• Isotype, allotype, idiotype…

– implies that epitopes (at least experimentally) are proteins

– proteins are specified by genes

– how do genes specify the numerous, diverse, highly

specific immunoglobulins? (BIG
question!)

• Time to review
& take a 5’ break!