B-cell And T-cell

Receptors
Dr. Eman M. Qibi

The origin and function of B and T cells

 The multipotent stem cells found in the bone

marrow will differentiate into lymphoid and myeloid
cells in response to various cytokines and growth
factors.
 The common lymphoid progenitor cell gives rise to
B lymphocytes, T lymphocytes and natural killer
(NK) cells.
 B lymphocytes remain within the bone marrow to
complete their development.
 T lymphocytes leave the bone marrow and undergo
development within the thymus.
 From 1ry lymphoid organs B and T cells distributed
through lymph and blood to 2ry lymphoid organs :
(Lymph nodes,Tonsils, Spleen and Mucosal tissues in
lung and gut)
Important points
 The principal cellular components of innate immunity
(phagocytes neutrophils and monocytes/macrophages)
are blood cells that are recruited to sites of infection,
where they are activated by engagement of different
receptors. Some activated macrophages destroy microbes
and dead cells and other macrophages limit inflammation
and initiate tissue repair.
 In addition to providing early defense against infections,
innate immune responses provide signals that work
together with antigens to activate B and T lymphocytes.
 Microbes and microbial antigens that enter the body are
captured by antigen-presenting cells (APCs) to naive T
lymphocytes that recirculate through the lymphoid
organs.
 In the adaptive immune system, B and T lymphocytes
express different receptors that recognize antigens: [
membrane-bound antibodies on B cells and T cell
receptors (TCRs) on T lymphocytes ].

Adaptive immune response

B-cell And T-cell Receptors
 B and T lymphocytes express different receptors that
recognize antigens:
 The mature, naïve B lymphocyte, (i.e. the ready-to-respond
form), expresses 2 isotypes of antibody or immunoglobulin
called IgM and IgD within its surface membrane.
 and The mature, naive T cell expresses a single genetically
related molecule, called the T-cell receptor (TCR), on its
surface.
 The principal function of cellular receptors in the immune
system, is to detect external stimuli (antigens) and trigger
responses of the cells on which the receptors are expressed.
 Both of these types of antigen receptors are encoded within
the immunoglobulin superfamily of genes and are expressed
in literally millions of variations in different lymphocytes as a
result of complex and random rearrangements of the cells’
DNA.

Antigen Receptors of Mature Lymphocytes

Antigen recognition

 membrane-bound antibodies, which serve as the

antigen receptors of B lymphocytes, can recognize
many types of chemical structures, while most T
cell antigen receptors recognize only peptides
bound to major histocompatibility complex (MHC)
molecules and this specificity of T cells restricts
their recognition to only cell-associated microbes.

 Although each clone of B lymphocytes or T lymphocytes

recognizes a different antigen, the antigen receptors transmit
biochemical signals that are fundamentally the same in all
lymphocytes and are unrelated to specificity.
B Cell receptor
 Antibodies exist in two forms either as membrane-
bound antigen receptors on B cells or as secreted
proteins.
 Secreted antibodies are present in the blood and
mucosal secretions, where they function to defend
against microbes (i.e., they are the effector molecules
of humoral immunity).
 membrane-bound antibodies on B cells recognize
antigens to initiate the responses.
 secreted antibodies (proteins secreted by antigen
stimulated B cells that have differentiated into
antibody-secreting plasma cells) neutralize and
eliminate microbes and their toxins in the effector
phase of humoral immunity.

Antibodies (Immunoglobulin) structure

 The core structure of antibodies consists of two identical

heavy chains and two identical light chains, forming a
disulfide-linked complex (the basic monomeric unit for each
of the distinct antibody molecules destined to circulate
freely in the serum).
 Each chain consists of a variable (V) region, which is the
portion that recognizes antigen, and a constant (C) region,
which provides structural stability and, in heavy chains,
performs the effector functions of antibodies.
 The V region of one heavy chain and of one light chain
together form the antigen-binding site, and thus the core
structure has two identical antigen-binding sites.
Structure of immunoglobulin

T Cell receptor (TCR)

 TCRs exist only as membrane receptors on T cells
and are not secreted.
 In cell-mediated immunity, the effector function of
microbe elimination is performed by T
lymphocytes themselves and by other leukocytes
responding to the T cells.
 The antigen receptors of T cells are involved only
in antigen recognition and T cell activation, and
these proteins are not secreted and do not
mediate effector functions.
T cell receptors structure
 T cell receptors consist of an α chain and a β
chain. Each chain contains one V region and one C
region, and both chains participate in the
recognition of antigens, which for most T cells are
peptides displayed by MHC molecules.
 The V regions of immunoglobulin (Ig) and TCR
molecules contain hypervariable segments, also
called complementarity-determining regions
(CDRs), which are the regions of contact with
antigens.

T cell receptor structure

Notes
 During their maturation, lymphocytes are selected
to survive at several checkpoints; only cells with
complete functional antigen receptors are
preserved and expanded. In addition,T
lymphocytes are positively selected to recognize
peptide antigens displayed by self MHC molecules
and to ensure that the recognition of the
appropriate type of MHC molecule matches the
coreceptor preserved.
 Immature lymphocytes that strongly recognize self
antigens are negatively selected and prevented
from completing their maturation, thus eliminating
cells with the potential of reacting in harmful ways
against self tissues.