Bcells
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Transcript of Bcells
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B-cell Function and Characterisatics:B cells comprise approximately 35
percent of the circulating lymphcytes and primarily are responsible for
humoral immunity (i.e., production of specific serum immunoglobulins
directed against various environmental antigens).B cells function in
antibody production in two distinct ways.
In the first and clearly most simple case, antigens bind directly to
the B cells surface; B cells then undergo a clonal proliferation
followed by terminal differentiation into plasma cells. Plasma cells
are highly specialized for the secretion of immunoglobulins.
In the second and more complex case, antigens are bound to the surface
immunoglobulins of helper T cells. Next, these antigen-antibody
complexes are released from helper T cells and bound to macrophages.
Finally, the B cells interact specifically with stimulated macrophages
and subsequently undergo a clonal proliferation and plasma cell
differentiation.
Certain B cells persist after initial exposure to an antigen and exist
in the form of memory B cells. These cells can undergo a rapid clonal
expansion if a person is exposed again, even years later, to the sameantigen.
B cells are most heavily concentrated in the germinal centers of
aggregates of lymphoid tissue. For example, B cells are found in large
numbers in the cortical aggregates in lymph nodes and in the white pulp
of the spleen.
T cell development: Fetal stem cells are destined to become T cells,
which enter the thymus and proliferate there. These immature T cells
(called thymocytes while in the thymus for the periphery as mature T
cells).
During T cell development in the thymus, several changes occur.
1. Some type of selection process occurs, which favors the
proliferation of thymocytes that are restricted by self-MHC molecules.
That is, thymocytes are selected for their ability to recognize
antigens associated with molecules of the same MHC type.
2. Precursors of both helperT (Th) cells (MHC class II-restricted)
and cytotoxic T (Tc)lymphocyte (MHC class I- restricted) are
selected.
3. Current evidence suggests that cortical thymic epithelial cells,
which express both class I and class II MHC glycoproteins are
important in this selection event; the mechanism is still unknown.
General Characteristics of T cells:
a. T cell surface markers:1. Monoclonal antibody techniques have identified
molecules on the T cell membrane that function chiefly
as receptors.
2. These surface molecules include:
a. Class I and class II MHC molecules
b. Thy 1, Ly1, Ly2,3 and L3T4 in mice.
c. CD (cluster of differentiation) antigens (e.g., CD3,
CD4, and CD8) in humans.
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3. As a thymocyte differentiates toward a particular T
cell subtype, it acquires certain CD antigens in its
membrane and loses others. Thus, the T cell subsets
can be distinguished by their CD markers.
4. CD3, CD2, and CD5 are found on most peripheral blood T
cells.
a. CD3 is a heteropolymer with at least five
polypeptide chains; it appears late in
differentiation when the cells are becoming
immunocompetent.
i. CD3 is associated with the T cell receptor for
antigen and it is important in intracellular
signaling to initiate an immune response once
the cell has interacted with a homologous
epitope.
ii. CD3 is not directly involved in
antigen recognition, but antibodies against CD3
will block the antigen-specific activation of T
cells.
b. CD2 (the SRBC receptor) is responsible for
resetting of sheep red blood cells (SRBCs) inthe E-rosette assay for T cell enumeration.
c. CD5 is expressed on all T cells and on a subset
of B cells that appear to be predisposed to
autoantibody production.
5. CD4 and CD8 are present on different effector T cells
and on a subset of B cells that appear to be
predisposed to autoantibody production.
6. Antiserum against certain of the membrane markers
(e.g., against CD3) is immunosuppressive and has been
used to prevent rejection of transplanted tissues.
b. The T cell receptor for antigen
1. T cell have an antigen-specific receptor that
functions as the antigen recognition site. This surface
component , the T cell receptor (TCR), bears significant
structural homology with the Fab portion of an antibody
molecule.
2. Structure and Function of TCR:
a. The TCR is a heterodimer.
i. It consists of two nonidentical polypeptide
chains, an chain (about 45kDa) and a chain (about 40
kDa), linked together by disulfide bonds.
ii. Both chains of the heterodimer are variable; there may
be more variability in the smaller () chain.
b. The TCR contains idiotypic determinants similar to those
of immunoglobulin molecules. Hypervariability occurs in
particular areas of each polypeptide chain in a manner
analogous to the complementarity-determining regions(CDRs) of immunoglobulin molecules.
c. The TCR heterodimer is noncovalently linked in the T
cell membrane to the ,, and chains of the CD3
molecule.
d. The TCR-CD3 complex apparently makes contact with both
the antigen and a portion of the MHC molecule. Different
portions of the hypervariable regions of the and
chains interact with:
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i. The helical sides of the epitope-binding cleft of the
MHC molecule.
ii. The epitope lying on the floor of the
cleft.
e. CD4 or CD8 molecules (depending on the T
cell subset) also contact a portion of the
MHC molecule.