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Billingham, Rupert (1921–2002) 107 biologicals
Target
cell
Bifunctional antibody
Bifunctional antibody.
Cytotoxic
T Lymphocyte
Bispecific antibodies that bind to both effector and target cells
can activate the effector cell and guarantee intimate contact
between effector and target cells. The three basic techniques to
prepare bispecific molecules are (1) heteroconjugate bispecific
antibodies produced by chemical linkage of two immunoglobulin
molecules with different binding specificities; (2) hybridoma-specific
antibodies formed by hybridomas produced by
fusing two lymphocytes that synthesize antibodies of different
specificities; and (3) bispecific molecules produced by genetic
engineering which permits the insertion, within or adjacent to
the genes encoding an immunoglobulin molecule, of oligonucleotides
encoding another immunoglobulin, a desired
immunogenic epitope, or an epitope responsible for interaction
with a viral antigen. Bispecific antibodies were developed to
redirect or enhance immune effector responses toward tumors
and induce killing of target cells in a non-MHC-restricted
manner. One limb of the bispecific antibody recognizes a
cell-surface antigen on the cytotoxic effector cell, while the
other limb is specific for a tumor antigen. Recombinant DNA
technology has permitted the generation of bispecific scFv,
minibodies, diabodies, and multivalent bispecific antibodies.
Single-chain bispecific antibodies are composed of linked
variable domains fused to human Fc domains. Miniantibodies
comprise an scFv joined by a linker to a dimerization domain
while diabodies exploit the intrinsic nature of VH and VL
within an Fv to pair.
Billingham, Rupert (1921–2002)
Together with P.B. Medawar proved that the rejection
of grafts between unrelated individuals, i.e., allografts
or homografts, has an immunological basis. Pioneer of
acquired immunological tolerance reported in classic paper
in Nature 1953.
binding constant
Refer to association constant.
binding protein
Also called immunoglobulin heavy chain-binding protein.
binding site
The paratope area of an antibody molecule that binds antigen
or the part of a T cell receptor that is antigen binding.
biochemical sequestration
Antigenic determinants that are hidden in a molecule may
be unable to act as immunogens or react with antibody.
Structural alterations in the molecule may render them
identifiable and capable of serving as immunogens.
Rupert Billingham, colleague of P.B. Medawar, who was also a pioneer in
immunologic tolerance.
biogenic amines
Nonlipid substances of low molecular weight, such as
histamine, that have an amine group in common. Biogenic
amines are stored in the cytoplasmic granules of mast cells,
from which they may be released to mediate the biological
consequences of immediate hypersensitivity reactions. Also
called vasoactive amines.
biolistics
The coating of small particles such as colloidal gold with an
agent such as a drug, nucleic acid, or other substance to be
conveyed into a cell. A helium-powered gun is employed to
fire particles into the recipient’s dermis.
biological false-positive reaction
A positive serological test for syphilis, such as the VDRL
(Venereal Disease Research Laboratory) serological test produced
by the serum of an individual who is not infected with
Treponema pallidium. The reaction is attributable to antibodies
reactive with antigens of tissues such as the heart, from
which cardiolipin antigen used in the test is derived. The sera
of patients with selected autoimmune diseases, including
systemic lupus erythematosus (SLE), may contain antibodies
that give biological false-positive results for syphilis.
biological response modifiers (BRMs)
A wide spectrum of molecules such as cytokines that
alter immune responses. They include substances such as
interleukins, interferons, hematopoietic colony-stimulating
factors, tumor necrosis factor, B lymphocyte growth and
differentiating factors, lymphotoxins, and macrophageactivating
and chemotactic factors, as well as macrophage
inhibitory factor, eosinophil chemotactic factor, osteoclast
activating factor, etc. BRMs may modulate the immune
system of a host to augment antitumor defense mechanisms.
Some have been produced by recombinant DNA technology
and are available commercially. An example is α interferon
used in the therapy of hairy cell leukemia.
biologicals
Natural or engineered proteins employed to activate or
interefere with the proliferation, metabolism, or functioning
of normal or neoplastic cells. Substances used for therapy
that include antitoxins, vaccines, products prepared from
pooled blood plasma, and biological response modifiers
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