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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.