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We are confronted with different infectious agents on a daily basis, as a result, immune
responses come in a number of ways and are targeted towards the nature of the pathogen that
provoked the response in the first place.
Microorganisms are sometimes able to resist phagocytosis. If small amounts of antibody are
added the phagocyte springs into action. It does so through the recognition of two or more
antibody molecules bound to the microbe, using specialized Fc receptors on the cell surface
of the phagocyte
As mentioned earlier, antibody molecules carry out two principal functions in immune
defense. The first function is to recognize and bind to foreign material (antigen). This
generally means binding to molecular structures on the surface of the foreign material
(antigenic determinants) that differ from molecular structures made by the cells of the host.
These antigenic determinants are usually expressed in multiple copies on the foreign
material, such as proteins or carbohydrates on a bacterial cell surface or envelope spikes on
the surface of a virus. Antibodies of a single host can recognize a huge variety of different
molecular structures – a human is capable of producing antibodies against billions of
different molecular structures. This is described as antibody diversity and is necessary to
respond to the huge diversity of molecular structures associated with (often highly mutable)
pathogens.
The simple act of antibody binding may be sufficient to inactivate a pathogen or render a
toxin harmless. For instance, antibody coating of a virus can prevent entry into target cells
and thereby “neutralize” the virus. However, in many instances, a second function of the
antibody molecule is deployed to trigger the elimination of foreign material. In molecular
terms, this involves the binding of certain molecules (effector molecules) to antibody‐coated
foreign material to trigger complex elimination mechanisms, such as the complement system
of proteins, phagocytosis by host immune cells (e.g., neutrophils and macrophages), and
antibody‐dependent cellular cytotoxicity (ADCC) by NK cells. These effector systems are
mainly triggered only by antibody molecules clustered together such as on a foreign cell
surface and not by free unliganded antibody.
The B lymphocyte response to a single antigen may include specific antibody molecules of
all five immunoglobulin classes. Antibodies of different classes may show identical
antigen-binding specificities and thus presumably may possess identical variable (VH + VL)
regions; however, the CH regions mediate different secondary effector functions
1) Complement activation
✓ The classical pathway of complement activation is initiated by the binding of the Cl1
subcomponent to the IgM or IgG component of an antigen-antibody complex.
✓ IgM and IgG can activate alternative pathway under certain circumstances but it is
unclear whether other immunoglobulin classes do so in vivo.
2) Binding to cells
Some immunoglobulins are bound to cell surfaces. Phagocytic cells (monocytes,
macrophages and polymorphs) have receptors which recognize sites in the constant regions
of IgG molecules. Foreign particles coated with IgG antibodies are bound by these receptors,
so triggering rapid phagocytosis (TB infection).
3) Placental transfer
The placental transfer of immunoglobulins provides the newborn infant with an adequate
repertoire of antibody specificities. In humans, only IgG antibodies cross the placenta: this is a
property of the Fc region which interacts with receptors on placental syncytiotrophoblast. The
Fab fragment, although one-third the size of the whole molecule, is not transferred.
.
The structure of the immunoglobulin classes:
▪ The immunoglobulin classes fulfill different roles in immune defense and this can be
correlated with differences in their structures as organized around the four‐chain Ig
domain arrangement
▪ IgG: is monomeric and the major antibody in serum and non-mucosal tissues, where it
inactivates pathogens directly and through interaction with effector triggering molecules,
such as complement and Fc receptors. In IgG, the Fab arms are linked to the Fc by an
extended region of polypeptide chain known as the hinge. This region tends to be
exposed and sensitive to attack by proteases that cleave the molecule in to its distinct
functional units arranged around the four‐chain structure.
✓ The light chains exist in two forms, known as kappa (k) and lambda (λ). In humans, k
chains are somewhat more prevalent than λ; in mice, λ chains are rare.
✓ The heavy chains can also be grouped into different forms or subclasses, the number
depending upon the species under consideration
• IgG, IgD and IgE are each made up of one subunit (monomer).
• IgG and IgE are generally monomeric, whereas IgM occurs as a pentamer
✓ Most of the IgA in normal serum is composed of a single subunit (monomeric IgA), but
the rest, and much of the IgA in secretions, consists of two subunits (Dimer).
✓ IgA occurs predominantly as a monomer in serum and as a dimer in seromucous
secretions (e.g.the lumen).
✓ Serum IgM is a pentamer of five subunits and therefore has 10 antigen-binding sites.
✓ Dimers and pentamers are stabilized by a further polypeptide (J chain) synthesized by
plasma cells
✓ The differences are most pronounced in the Fc regions of the antibody classes and this
leads to the triggering of different effector functions on binding to antigen.
✓ For example, IgM recognition of antigen might lead to complement activation, whereas
the recognition of same antigen by IgE might lead to anaphylaxis and mast cell
degranulation (Degranulation is a cellular process that releases antimicrobial cytotoxic or
other molecules from secretory vesicles called granules found inside some cells).
Assignment:
1) Draw the structures of the immunoglobulin classes and label them appropriately.
1) Thompson E.G., Husney A, Gabica M.J. Healthwise staff Medical review, University of
Michigan, 2019.