Page 20 - Clinical Immunology_ Principles and Practice ( PDFDrive )

6 Part one Principles of Immune Response

V H V H
V L C µ C µ V L
C L C L
C µ C µ
V V α α α β
C µ C µ α β 1 2 1 1
C µ C µ C α C β β m α 3 α 2 β 2
2

Cell membrane
migM αβTCR HLA HLA
class I class II
FIG 1.1 Antigen-Binding Molecules. Antigen-binding pockets of immunoglobulin (Ig) and T-cell
receptor (TCR) comprise variable (V) segments of two chains translated from transcripts that
represent rearranged V(D)J or VJ gene elements. Thin red bars designate two of the complementarity
determining regions (CDRs) that form portions of the Ig antigen-binding site. The red ovals with
thick red bars designate the regions of very high sequence variability in both Igs and TCRs that
are generated by recombination of the 3’-end of the V gene element with the D and J gene
elements or with the J gene element. In the Ig molecule this is designated CDR3. Antigen-binding
pockets of Ig molecules are formed by the three-dimensional folding of the heavy and light chains
that juxtapose the CDRs of one heavy chain and one light chain. Antigen-binding grooves of
MHC molecules are formed with contributions from α 1 and β 1 domains of class II molecules and
from α 1 and α 2 domains of class I molecules. All of these molecules are members of the
immunoglobulin superfamily. C, constant-region domain; β 2 , beta-2 microglobulin; mIgM, membrane
immunoglobulin M; HLA, human leukocyte antigen; MHC, major histocompatibility complex.

distinction between commensal (not dangerous) and potentially immunological memory. This phenomenon derives from the
pathogenic (dangerous) microbes. fact that after an initial encounter with antigen clones of lym-
T lymphocytes generally recognize antigens as a complex phocytes that can recognize the antigen proliferate and differenti-
of short linear peptides bound to self-MHC molecules on the ate into effector cells, most of which ultimately are consumed
surfaces of APCs (Chapter 6). The source of these peptides can or undergo apoptosis, and a smaller population of long-lived
be either extracellular or intracellular proteins and derived from memory cells. These memory cells constitute a pool of cells larger
either self or foreign (e.g., microbial) molecules. With the excep- than the initial naïve responders. They can elicit a greater and
tion of superantigens (see below), T cells neither bind antigen more rapid response upon subsequent antigen encounter. These
in native conformation nor recognize free antigen in solution. two hallmarks of adaptive immunity, clonal specificity, and
The vast majority of antigens for T cells are oligopeptides. immunological memory provide a conceptual foundation for
However, the antigen receptors of NKT cells can recognize lipid the use of vaccines in prevention of infectious diseases (Chapter
and glycolipid antigens that are presented to them by MHC-like 90). Immunological memory involves not only the T cells charged
CD1 molecules. 14 with antigen recognition but also the T cells and B cells that
Antigen recognition by T cells differs fundamentally from mediate the efferent limb of an inflammatory response. In its
that by antibodies, which are produced by B lymphocytes and attack on foreign targets, the immune system can exhibit exquisite
their derivatives. Antibodies are oriented toward recognition specificity for the inducing antigen, as is seen in the epitope-
of extracellular threats and, unlike T cells, can bind complex specific lysis of virus-infected target cells by cytolytic T cells.
macromolecules and can bind them in their native conformation
either at cell surfaces or in solution. Moreover, antibodies show ANTIGEN-BINDING MOLECULES
less preference for recognition of proteins; antibodies against
carbohydrates, nucleic acids, lipids, and simple chemical moieties
can be readily produced. Although B cells can also be rendered KeY ConCePtS
unresponsive by exposure to self-antigens, particularly during Features of the Immunoglobulin (Ig) Superfamily
differentiation in bone marrow, this process does not define
foreignness within the context of self-MHC recognition. • Large family of ancestrally related genes (more than 100 members)
• Most products involved in immune system function or other cell–cell
interactions
Clonal Basis of Immunological Memory • Ig superfamily members have one or more domains of ~100 amino
An essential element of self/nonself discrimination is the clonal acids, each usually translated from a single exon
nature of antigen recognition. Although the immune system can • Each Ig domain consists of a pair of β-pleated sheets usually held
recognize a vast array of distinct antigens, all of the receptors of together by an intrachain disulfide bond
a single T cell or B cell (and their clonal progeny) have identical
antigen-binding sites and hence a particular specificity (Chapter Three sets of molecules are responsible for the specificity of
4). A direct consequence is the capacity for antigen-driven adaptive immune responses by virtue of their capacity to bind