Page 520 - Review of Medical Microbiology and Immunology ( PDFDrive )

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mebooksfree.com mebooksfree.com mebooksfree.com We inherit one set of class I and one set of class II genes 509 mebooksfree.com
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CHAPTER 58 Cellular Basis of the Immune Response
molecules, such as peptides, polysaccharides, nucleic acids,
from each parent. Therefore, our cells can express as many
and small molecules (e.g., drugs such as penicillin).
These differences between T cells and B cells explain the
as six different class I and six different class II proteins (see
Chapter 62). Furthermore, there are multiple alleles at each
hapten-carrier relationship described in Chapter 57. To
stimulate hapten-specific antibody, the hapten must be
gene locus. Each of these MHC proteins can present pep-
covalently bound to the carrier protein. The hapten binds
part, our ability to respond to many different antigens.
to the IgM receptor on the B-cell surface. That IgM is spe-
cific for the hapten, not the carrier protein. The hapten-
Memory T Cells
carrier conjugate is internalized and the carrier protein tides with a different amino acid sequence. This explains, in
mebooksfree.com mebooksfree.com mebooksfree.com ously for many years after the initial exposure to a microbe mebooksfree.com
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processed into small peptides that are presented in associa-
Memory T (and B) cells, as the name implies, endow our
tion with class II MHC proteins to a helper T cell bearing a
host defenses with the ability to respond rapidly and vigor-
receptor for that peptide. The helper T cell then secretes
lymphokines that activate the B cell to produce antibodies
or other foreign material. This memory response to a spe-
to the hapten.
cific antigen is due to several features: (1) many memory
When the antigen–MHC protein complex on the APC
cells are produced, so that the secondary response is greater
interacts with the TCR, a signal is transmitted by the CD3
than the primary response, in which very few cells respond;
protein complex through several pathways that eventually
(2) memory cells live for many years or have the capacity to
lead to a large influx of calcium into the cell. (The details of
reproduce themselves; (3) memory cells are activated by
the signal transduction pathway are beyond the scope of
this book, but it is known that stimulation of the TCR acti-
than do naïve, unactivated T cells; and (4) activated mem-
vates a series of phosphokinases, which then activate phos-
ory cells produce greater amounts of interleukins than do
pholipase C, which cleaves phosphoinositide to produce smaller amounts of antigen and require less costimulation
naïve T cells when they are first activated.
inositol triphosphate, which opens the calcium channels.)
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mebooksfree.com mebooksfree.com mebooksfree.com The TCR for antigen consists of two polypeptides, alpha mebooksfree.com
Calcium activates calcineurin, a serine phosphatase. Calci-
T-Cell Receptor
neurin moves to the nucleus and is involved in the activa-
tion of the genes for IL-2 and the IL-2 receptor. (Calcineurin
2
and beta, which are associated with CD3 proteins.
function is blocked by cyclosporine, one of the most effec-
tive drugs used to prevent rejection of organ transplants
TCR polypeptides are similar to immunoglobulin
heavy chains in that (1) the genes that code for them are
[see Chapter 62].)
formed by rearrangement of multiple regions of DNA (see
The end result of this series of events is the activation of
the helper T cell to produce various lymphokines (e.g., IL-2),
Chapter 59); (2) there are V (variable), D (diversity), J (join-
ing), and C (constant) segments that rearrange to provide
as well as the IL-2 receptor. IL-2, also known as T-cell growth
factor, stimulates the helper T cell to multiply into a clone of
100 million different receptor proteins; (3) the variable
antigen-specific helper T cells. Most cells of this clone per-
regions have hypervariable domains; and (4) the two genes
form effector and regulatory functions, but some become
memory cells (see later), which are capable of being rapidly diversity, giving rise to an estimated number of more than
(RAG-1 and RAG-2) that encode the recombinase enzymes
mebooksfree.com mebooksfree.com mebooksfree.com which means that hundreds of millions of different T cells mebooksfree.com
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activated upon exposure to antigen at a later time. (Cytotoxic
that catalyze these gene rearrangements are similar in T cells
T cells and B cells also form memory cells.) Note that IL-2
and B cells.
stimulates CD8 cytotoxic T cells as well as CD4 helper T cells.
Note that each T cell has a unique TCR on its surface,
Activated CD4-positive T cells also produce another lympho-
exist in each person. Activated T cells, like activated B cells,
kine called gamma interferon, which increases the expres-
clonally expand to yield large numbers of cells specific for
sion of class II MHC proteins on APCs. This enhances the
that antigen.
ability of APCs to present antigen to T cells and upregulates
the immune response. (Gamma interferon also enhances the
Although TCRs and immunoglobulins (antibodies) are
microbicidal activity of macrophages.)
analogous in that they both interact with antigen in a
The process of activating T cells does not function as a
tant ways: (1) it has two chains rather than four, and (2) it
simple “on–off” switch. The binding of an epitope to the
recognizes antigen only in conjunction with MHC pro-
TCR can result in either full activation, partial activation in
teins, whereas immunoglobulins recognize free antigen.
which only certain lymphokines are made, or no activation, highly specific manner, the TCR is different in two impor-
mebooksfree.com mebooksfree.com mebooksfree.com 2 These TCRs are unusual because they do not require that antigen be pre- mebooksfree.com
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depending on which of the signal transduction pathways is
stimulated by that particular epitope. This important
observation may have profound implications for our under-
standing of how helper T cells shape our response to infec-
Some TCRs have a different set of polypeptides called gamma and delta.
tious agents.
sented in association with MHC proteins. Gamma/delta T cells constitute
There are three genes at the class I locus (A, B, and C)
approximately 10% of all T cells. Some of the T cells bearing these TCRs
and three genes at the class II locus (DP, DQ, and DR).
are involved in cell-mediated immunity against M. tuberculosis.
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