FIVE MAJOR CLASSES OF IMMUNOGLOBULINS  May initiate polymerization by stabilizing Fc

sulfhydryl groups so that crosslinking can take place

Immunoglobulin G (IgG)  Mol.wt. Is approximately 15,000
 Predominat Ig in humans (75 to 80% of the total serum Igs)
 Longest half-life (23 to 25 days)
 Four major subclasses:
1. IgG1 – 66%
2. IgG2 – 23%
3. IgG3 – 7%
4. IgG4 – 4%
 Subclasses differ mainly in the number and position of the
disulfide bridges between the gamma chains
 Variability in the hinge region region affects the ability to
reach for antigen and the ability to initiate important
biologic functions
- IgG3 has the largest hinge region and the largest number
of interchain disulfide bonds, therefore most efficient at  One is present per pentamer
binding complement  Assumes a starlike shape with a total of 10 functional
- IgG2 and IgG4 have the shorter hinge segments, which binding sites (5 of these are used unless antigen is extremely
tend to make them poor mediators of complement activation small)
 Major Functions of IgG:  Assumes a three-dimensional structure which is crablike
1. Providing immunity for the newborn when combined with an antigen
because IgG can cross the placenta (all though  Tend to have a low affinity for antigen due to its high
IgG2 is least efficient) valency
2. Fixation of complement  Found mainly in the intravascular pool (large size) and not
3. Opsonization, or coating of antigen for in other body fluids or tissues)
enhanced phagocytosis  Incapable of crossing the placenta
4. Neutralization of toxins and viruses  IgM is known as the primary response antibody because it is
5. Participation in agglutination and the first to appear after antigenic stimulation, and the first to
precipitation reactions appear in the maturing infant
 Macrophages, monocytes, and neutrophils have receptors on  Synthesized only as long as antigen remains present (no
their surfaces that are specific for the Fc region of the IgG memory cells for IgM)
(enhances contact between the antigen and phagocytic cells)  Primary response – predominantly IgM; long lag
 IgG has a high diffusion coefficient (allows it to enter phase
extravascular spaces more readily thus play a major role in  Secondary response – mainly IgG; shortened lag
neutralization of toxins and viruses period; more rapid increase in antibody titer
 Agglutination and precipitation reactions take place in vitro  Functions of IgM:
(better at precipitation because it involves small soluble 1. Complement fixation
particles which are more easily brought together by the
 Most efficient in triggering the classical
relatively small IgG molecule)
complement pathway because a single
molecule can initiate the reaction as a result of
Immunoglobulin M (IgM)
its multiple binding sites
 A macroglobulin
 (most important function)
 Sedimentation rate of 19 S (mol. wt. of approximately
2. Agglutination
900,000)
 Most efficient because of the larger number of
 Half life : 10 days
binding sites esp with multivalent antigens,
 Accounts for between 5 to 10% of all serum
thus a potent defense against many bacterial
immunoglobulin
diseases
 When subjected to treatment with mercaptoethanol, it
3. Opsonization
dissociates into five 7 S, each having a mol.wt. of 180,000
4. Neutralization of toxins
and a four-chain structure that resembles IgG
 An additional role for IgM is that of a surface receptor for
 Mol. wt. of μ chain chain is 70,000 (576 Aas and one more
antigen
constant domain on the γ chain)
 Two forms:
Immunoglobulin A (IgA)
1. Pentameric form – found in secretions
 A monomer with a mol.wt. of 160,000
2. Monomer form – occurs on the surface of B cells
 Sedimentation coefficient of 7 S
 The five monomeric units are held together by a J or
 Migrates between the γ and β regions on eletrophoresis
Joining chain (glycoprotein with a number of cysteine
 H chain (α) has a mol.wt. Between 55,000 to 60,000 (472
residues)
AAs)
 Subclasses:
 Joining or J chain
1. IgA1 – primary monomer found in serum
 Cysteine residues serve as linkage points for disulfide
2. IgA2
bonds between two adjacent monomers
- Differ in content by 22 AAs, 13 of which located in the
 Linkage occurs at the carboxy-terminal end of two of
hinge region (deleted in IgA2)
the μ chains

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 IgA2
 More resistant to bacterial proteinases (cleaved
IgA1)
 Has disulfide bond that covalently link together the
L chains rather than the H chains
 Also found as a dimer (2 monomers held together
by a J chain with a mol.wt. Of 15,000) in body
secretions along the respiratory, urogenital, and
intestinal mucosa, and in milk, saliva, tears, and
sweat
 Serves to keep antigens from penetrating further
into the body
 Secretory IgA is synthesized in plasma cells found
mainly in mucosal associated lymphoid tissue and
released in dimeric form
 J chain regulates the degree of polymerization and
may also help in transport to mucosal secretions
 Synthesized at a rate that is approximately twice that
of IgG (mainly in secretory form; serum conc. is
much lower)
 Secretory Component (SC)
 Mol.wt. Of 100,000
 Later attached to the Fc portion of the α chains
 Consists of five immunoglobulin-like domains
 Derived from epithelial cells found in close proximity
to the plasma cells (plasma cells that secrete IgA
actually home to subepithelial tissue, where IgA can
bind as soon as it is released from the plasma cells)
 serves as a specific receptor for IgA
 Once binding takes place, IgA and SC precursor are
both taken inside the cell and released to the opposite
surface by transcytosis
 The vesicle carrying IgA and the SC receptor fuses
with the membrane on the opposite side of the cell,
and a small fragment of SC is cleaved to liberate the
IgA dimmer with the remaining SC
 The SC may thus act to facilitate transport of IgA to
mucosal surfaces
 Also makes the dimer resistant to enzymatic
digestion
 Functions of IgA
1. To patrol mucosal surfaces and act as a first line of
defense
2. Plays an important role in neutralization of toxins produced
by microorganisms
3. Helps to prevent bacterial adherence to mucosal surfaces
 Complexes of IgA and antigen are easily trapped in mucus
and then eliminated by the ciliated epithelial cells of the
respiratory or intestinal tract
 IgA is not capable of fixing the complement by the classical
pathway, though aggregation of immune complexes may
trigger the alternate pathway (lack of activation may assist in
clearing of antigen without triggering an inflammatory
response, thus minimizing tissue damage)
 Neutrophils, monocytes, and macrophages possess specific
receptors to IgA
- Binding triggers a respiratory burst and
degranulation (indicating that both types are capable of
acting as opsonins)
 Sabin vaccine (oral immunization)
- Demonstrates effectives of IgA’s protective role on
mucosal surfaces
 Immunoglobulin D (IgD)
 Discovered in 1965
 Extremely scarce in serum (0.2% of total Igs)
 Synthesized at a low level
 Half-life is only 2 to 3 days
 Mol. Wt. of approximately 184,000
 Migrates as a fast γ protein
 The δ H chain has a mol.wt. of 62,000 and appears to
have an extended hinge region (58 AAs)
 Most IgD present is found on the surface of
immunocompetent by unstimulated B lymphocytes
 The second type of immunoglobulin to appear
 May play a role in activation of B cells
 An ideal responder to antigen because of its high level
of surface expression and intrinsic flexibility
 Cells bearing both IgM and IgD receptors are capable
of responding to T cell help and switching to synthesis
of IgG, IgA, or IgE
 Has an unusually long hinge region thus more
susceptible to proteolysis (maybe the main reason for
shorter half-life)
 Binding of antigen also promotes cleavage, and
subsequent changes in the Fc region bound to the B cell
may help to trigger proliferation of that cell
 Does not appear to serve protective function in the
serum
 Does not bind complement
 Does not bind to neutrophils or macrophages
 Does not cross the placenta
 Immunoglobulin E (IgE)
 The least abundant Immunoglobulin in the serum
(0.004% of the total serum Igs)
 An 8S molecule with a mol.wt. of 190,000
 The ε H chain is composed of around 550 AAs
distributed over one variable and four constant
domains
 A single disulfide bond joins each ε chain to a L chain,
and two disulfide bonds link the H chains to one
another
 The most heat labile of the Igs (heating at 56°C
between 30 mins to 3 hours results in conformational
changes and loss of ability to bind target cells
 Does not participate in typical Ig reactions
 It is incapable of crossing the placenta
 Shortly after synthesis, it attaches to basophils and
tissue mast cells by means of specific surface proteins
(high affinity FCε RI receptors)
 Molecule binds at the CH4 domain on the Fc
region
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 While IgE appears to be a nuisance antibody, it may
serve a protective role by trigerring an acute
inflammatory reaction that recruit neutrophils and
eosinophils to the area to hep destroy invading antigens
that have penetrated IgA defenses
 Eosinophils especially play an important part in the
destruction of large antigens (parasitic worms) that
cannot be easily phagocytized